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JOSE CERDA Box 5: Rohy Pnol Bratton NYC Police Commissioner Methamphetamine Mutli-Cultural Programs Immigration - Fraternal Order of Police Firearm related juvenile use of drugs OVERSIZE ATTACHMENTS 16957 ENCLOSURES FILED NANA 14148 ROHYPNOL: THE DATE RAPE DRUG BACKGROUND Rohypnol, also known as "Roofies", is the brand name of the drug flunitrazepam. It is used in some countries to treat insomnia or anxiety but is illegal to produce or prescribe in the United States. Referred to as the "date rape drug", Rohypnol-- tasteless, odorless and easily dissolved in alcohol-- has increasingly been used by rapists to incapacitate their victims. Its use is also growing in popularity among young people. WHAT THE CLINTON ADMINISTRATION HAS DONE: 1. Customs Crackdown at the Ports of Entry On March 5, 1996, Secretary Rubin and Customs Commissioner Weise directed the U.S Department of Customs to seize all Rohypnol coming across the border. The Customs Service is now confiscating any amount of Rohypnol brought into the country by travelers, commercial shipments, or through the mail. 2. President Clinton's Anti-Gang and Youth Violence Act of 1996 In May of this year, President Clinton submitted legislation to Congress to further fight the scourge of Rohypnol. Among the other provisions to keep kids drug-free, the bill would give the Attorney General emergency authority to reclassify certain emerging drugs such as Rohypnol on the list of controlled substances-- thereby stiffening the penalties for their use. 3. President Clinton's Commitment to Sign H.R. 4137 Into Law President Clinton will sign into law H.R. 4137, the Drug-Induced Rape Prevention and Punishment Act of 1996. The bill will criminalize the use of Rohypnol-- or any illegal drug-- used with the intent to facilitate a violent crime. Enactment of the legislation will mean tougher penalties for such crimes, with criminals who use Rohypnol on their victims particularly targeted. The bill will also commission a six-month Drug Enforcement Agency study to determine whether Rohypnol should be reclassified. JAN-23-96 TUE 11:55 P.02 Rophynol (row-hip-nole) (flunitrazepam) I Known as "quaalude of "90s" in some parts of the country. Background benzodiazepine sedative (same family as Valium, Xanax, Halcion); manufactured by Roche Pharmaceuticals not legally available in U.S.; approved medicine in most other parts of the world prescribed as sedative (short-term treatment of insomnia & sleep disorders) Names: "rophies" "ropies" "roaches" "R2" "getting roached" Oral or pills crushed and put in joints Effects 10 times more potent than Valium; sedative/disinhibition effects are amplified in combination with alcohol 2mg tablet = drunken-like feelings, euphoria, disinhibidon, muscle relaxation, slowed 1 coordination, hangover. High doses = stupor. Unique property is its ability to cause amnesia (memory loss), particularly in combination with alcohol. This is a characteristic of many benzodiazepines. Late 1980s, cases of Halcion causing memory loss as long as 48 hours after use. Onset 20-30 minutes; lasts about 8 hours Risks: like all benzodiazepines, can produce dependence, rebound insomnia, withdrawal after extended use. Long-half life (slow elimination from body) 11 residual effects that can be dangerous if users take additional doses. Generally low OD potential, but high doses/drinking can cause significant respiratory & cardio depression. National Trends fastest growing drug problem among adolescents in south Florida; "epidemic" began over summer of 1993 Other "hotspots": southern Texas Users: club drug (young adults); alcohol extender (teenagers); ease comedown from crack/speed (street population in treatment) implicated in "date rape" cases in Florida JAN-23-96 TUE 11:56 P.03 Arizona First reports to CEWG in April 1995 of coming in over the border; Tucson, Yuma; mainly adolescents/teenagers taking it in combination with alcohol 4 ERs in Yuma reported during September 1995; all kids 41 DEA actions through November 1995 CEWG: no current reports of availability outside southern Arizona; use appears centered among high school students, so would expect eventual spread north 1 1 JAN 23 '96 11:57 E 602 844 8449 TO: P01 INTERVENTION SPECIALISTS EAST VALLEY ALCOHOLISM COUNCIL, INC. 554 S. Bellview Mess, Arizona 85204 Administrative Services (602) 962-7922 Clinical Services (602) 962-7711 OFFICERS: President FAX TRANSMISSION Rub Evans Vice President DATE: 1-23-96 TIME: 12:45 Larry Chesley AGENCY/CO. NAME: Secretary/Treasurer Patricia Miller ATTENTION: Dwight Vick Immediate Past President David 12. W. Shumway FAX NUMBER: 202-456-7028 TRANSMISSION CONSISTS OF 3 PAGES INCLUDING COVER. MEMBERS: William Benedict PROBLEMS? CALL 602-962-7922 Suzanne Dester EVAC'S FAX NUMBER IS 602-844-8449 Kerry Dunne Helen Enloe MESSAGE: Duright Per our R.R. Evans Conversation, here is the info Chris Fickas Pat Gilbert Falk to you soon Hon. R. Wayne Johnson Lars Jarvie John Hohman Kenneth Levine. D.O. Program Director John McKindles Lee Ann Schultz One Shill. M.D. EVAC Robert Soca 1 EXECUTIVE DIRECTOR: Rulph Hobe. M.A. People who attended the meeting: Ross Deck Edward Jurith Representatives from HHS Roche legal council member - Robert T. Angarola - Carter Drug Czar Don Kaiser - lawyer from Swiss office, now in Washington Rohypnol is produced by the Switzerland-based company, Roche. It is an international company with more than 80 production plants around the world. Two of their companies produce the drug, Rohypnol. They are located in Mexico City, Mexico and Bogota, Columbia. Kaiser presented the information. The Roche company heard of the drug's presence in late 1994. Hospital emergency rooms, treatment centers, and detoxification centers in Florida were admitting people with this drug in their blood stream or on their person. At first the company was not concerned. As these calls increased, the company began to worry as well. They did not know how it entered the country. Several options were explored. At first, Roche thought the people using the drug had obtained the drug through legal means. Kaiser mentioned the FDA and Customs agents allow someone to fill a prescription in another country as long as they do not have more than a 90-day supply. Foreign travelers use the drug as a sleep aid when travelling abroad and drank too much. Since this drug is legal by prescription in 62 foreign countries, this was of no major concern to Roche. The drug entered the U.S. through Florida with Caribbean- and Northeastern-based construction companies. Arriving to help PHOTOCOPY PRESERVATION rebuild Miami after Hurrican Andrew, the construction workers were working long hours and needed a drug to help them sleep heavily. They brought and took Rohypnol as prescribed. Eventually, the drug was mixed with alcohol to double the effects of the drugs. It became popular in bars and entered the street scene. However, Rohypnol was not the only drug to be abused in the area. Emergency rooms, detoxification centers and drug treatment facilities overflowed with people who were depressed and/or overworked after the hurricane. Roche is auditing its Mexican and Columbian plants internally for leaks. This is a strong possibility since the pills appear in bubble wrapping. Their audits show that no employee or groups of employees are removing the supplies or products outside of their facilities. Roche hired a drug research organization from Haight-Asbury in San Francisco to interview users in South Texas. Their findings showed that three types of people are more likely to take Rohypnol: opiate addicts, habitual users, first-time users. Opiate addicts use the drug to detoxify from all opiates. Basically, it stops most withdrawal symptoms. It is also a bridge drug. They use it until they can obtain more opiates. If used more than two weeks, the addict has simply switched addictions - from opiates to Rohypnol. Habitual users will use anything to get a "fix", including Rohypnol. The most predominate user is the first-time, naive user. They are usually kids who are rebelling against their parents. Roche stated their studies show most of the kids could not pick out Rohypnol from the pill charts they were shown. The company expects to use the Haight Asbury to conduct research in the South Florida area. However they expect some drug connection. There will be few similarities between the Florida and Texas epidemics. The company has agreed to limit access to pharmacies in or near Mexican border towns. In South Texas, the Haight Asbury study determined there is no major syndicate involvement in the distribution of Rohypnol. The users go to a Mexican physician located near a pharmacy and obtain a prescription. They take it to the nearest full-service pharmacist and get the pills. Most orders are not over 100 pills and are easily hidden from Customs agents (who would not be concerned about a prescription drug from Mexico in the first place). The company states they do not conclusively know how it is currently entering the Florida region. Roche is negotiating with Mexican officials in an effort to regulate the Rophynol market. Their biggest concern is their lack of understanding the Mexican laws. The company fears any serious involvement with the Columbian government. They do no want their employees or investigators to die. My Thoughts on Rhynopol Roche used this as a meeting to prevent any further media damage or government action this drug. They are scared that Roche will be associated with the production of a "date-rape drug". I think they are willing to regulate themselves so they can prevent damage control and government intervention. There were two cases in South Texas and Florida where the woman was raped after being exposed the Rohypnol. The kids call this violent activity, and getting high off the drug, as "roaching". The word Roche is printed on the tablet and the people mispronounce it. I have some serious misgivings about the validity and reliability of their research. First, they brought outsiders into South Texas to interview kids and users on the amount of the drug they used. Students are not generally honest about their use. They will lie to "look tough" or to cover up real usage amounts. While they did hire former users to interview them, these former users are outsiders to the South Texas. The interviewers are not familiar with the lifestyles and people. The interviewees will see them as "suckers" so they are more likely to lie than if it were someone they could identify with at the time. I asked the Roche representatives what were the other pills the users were shown. They all responded that various types were shown. Since generic forms of Rohypnol are just as easily available in Mexico as the Roche pill itself, I asked if they were pictured. There were no definitive answers. Furthermore, they stated they did not know if these users were taking the generic forms; yet, their findings in South Texas were conclusive. They did not know who the producers of the generic Rophynol market. Their only response was that 50 percent of men and 15 percent of the women could pick out the Roche pill. This made no sense to me and it was obvious I would get no further answers at this session. They were constantly referring to the drug as an oral drug. I asked them if their research showed that Rohypnol was smoked. Their studies did not show this occurrence at all. They stated the drug has no effect on the body once it is heated above 110 degrees. I stated the kids are still doing it and its use is increasing. When I called my friends in Phoenix, I learned some people crush the pill and mix it with marijuana. This is the second most common method of ingestion. The drug is not fatal unless the person ingests large amounts of alcohol and Rohypnol at the same time over a long period of time. Several people believe it is a loss leader by the black markets. They are attempting to gain more customers and they are targeting the three groups mentioned above. The Roche representatives stated they were the first company in American history to offer self-regulation to the government. They will work with the Mexican government to control the drug in border towns and foreign governments to prevent any leaks. They are also working with the Columbian government to prevent possible leaks from their country. The representatives agreed this would be difficult since the Columbian government is under siege. I agree. There was a brief mention of the product being shipped from other Central American or South American countries. No substantive investigations into this possibility were mentioned. This issue has become a race issue. Throughout 20th Century America, drug use has been a race issue. Opiate smoking was regulated in California because it was a Chinese tradition. The Chinese experienced racism throughout the region. No other opiate use was controlled. Marijuana and cocaine were regulated by state and local governments in an effort to control Hispanic and black populations. Once these problems involved white, middle-class Americans, federal involvement was demanded. When this was a South Florida/Caribbean problem, it was not a problem. When the drug entered Floridian, middle-class white American kids and young adults at dance bars, it became a problem. At this point in time, national citizen forces are not strongly aligned on this issue. Their influence at this time is not a factor in the policy making process. With media attention, this will grow without question. One salient, yet silent, factor in drug policy formulation is the alcohol and pharmaceutical industries. Tighter controls on these industries mean more money will be spent on drugs in the black market. Roche's meeting today falls along those lines. The only anomaly is Roche's advocating a mostly self-regulation measure. Roche is courting the Federal government in an effort to gain control of the situation without governmental action. In my opinion, it boils down to this - the Roche Company is afraid the American public will perceive this as the crack cocaine of the 1990s and the date rape pill. They gathered these groups of government employees together to encourage them to implement the company's wishes. My Recommendations - Take no legislative action at this time. If the WH attempts to control Rohypnol, it must look at controlling other benzodiazepines like valium. After the Maxine Water's arguments on crack cocaine VS. cocaine sentencing, it would renew old arguments. - All action should originate from the Executive Branch. - Publicity should be avoided. Children watch television. If the media portrays this as the "crack of the 1990s", demand will increase. Many people will want to see what it is like and will try it. This could result in higher Rohypnol addiction rates than we are currently experiencing. - The President should instruct the Secretary of State to contact his counterpart within the Mexican government. Since most of the South Texas business appears to be "mom- and-pop" store purchases in Mexico, the U.S. should encourage them to place stricter controls on the Rohypnol and its generic products in or near border towns. - The President should instruct the Secretary of the Treasury to notify Customs agents of the increased use of this drug and it is made accessible through their ports of entry. Roach Pharmaceutical cited several instances where they asked people to purchase the drug and smuggle it over the border. Others were asked to declare it. In all cases, no action was taken by Customs. - The President should instruct the Secretary of Health and Human Services to prepare a pamphlet for immediate distribution to all teachers, school administrators, treatment facilities, and emergency room personnel on this drug, its increased use among youth, and subsequent symptoms. Its use among habitual addicts should be mentioned as well. These groups are more likely to report is presence because of his involvement. Presidential attention to this issue will provide more reliable data available for study. Roche should be encouraged to apply for a patent on the drug. The only reason Rohpynol is not available on the American market today is due to its direct competition with valium. If they applied and received the rights to market the drug in the U.S., Roche could increase their profits on the drug by selling at a higher price in the United States than they would receive for Rohypnol in Mexico. The drug would be less alluring and the government could control its purity. The Federal government will monitor the drug. Rohypnol is not a drug like cocaine or heroin; therefore, it does not require a Schedule 1 rating. This will free the law enforcement agencies to monitor the influx of more serious drugs, like heroin and cocaine. If this becomes the "Crack of the 1990s", executive action will prove to the American people during an election year that President Clinton has made every attempt to control this problem without media attention. Media attention could attract children to the drug, making all actions counterproductive. If these policies are implemented, I think it will be a win-win situation for all involved. I would like to discuss these options with you. Thank you for the excellent oppotunity. I want to participate in any and all of these opportunities that occur. People who attended the meeting: Ross Deck Edward Jurith Representatives from HHS Roche legal council member - Robert T. Angarola - Carter Drug Czar Don Kaiser - lawyer from Swiss office, now in Washington Rohypnol is produced by the Switzerland-based company, Roche. It is an international company with more than 80 production plants around the world. Two of their companies produce the drug, Rohypnol. They are located in Mexico City, Mexico and Bogota, Columbia. Kaiser presented the information. The Roche company heard of the drug's presence in late 1994. Hospital emergency rooms, treatment centers, and detoxification centers in Florida were admitting people with this drug in their blood stream or on their person. At first the company was not concerned. As these calls increased, the company began to worry as well. They did not know how it entered the country. Several options were explored. At first, Roche thought the people using the drug had obtained the drug through legal means. Kaiser mentioned the FDA and Customs agents allow someone to fill a prescription in another country as long as they do not have more than a 90-day supply. Foreign travelers use the drug as a sleep aid when travelling abroad and drank too much. Since this drug is legal by prescription in 62 foreign countries, this was of no major concern to Roche. The drug entered the U.S. through Florida with Caribbean- and Northeastern-based construction companies. Arriving to help rebuild Miami after Hurricane Andrew, the construction workers were working long hours and needed a drug to help them sleep heavily. They brought and took Rohypnol as prescribed. Eventually, the drug was mixed with alcohol to double the effects of the drugs. It became popular in bars and entered the street scene. However, Rohypnol was not the only drug to be abused in the area. Emergency rooms, detoxification centers and drug treatment facilities overflowed with people who were depressed and/or overworked after the hurricane. Roche is auditing its Mexican and Columbian plants internally for leaks. This is a strong possibility since the pills appear in bubble wrapping. Their audits show that no employee or groups of employees are removing the supplies or products outside of their facilities. Roche hired a drug research organization from Haight-Asbury in San Francisco to interview users in South Texas. Their findings showed that three types of people are more likely to take Rohypnol: opiate addicts, habitual users, first-time users. Opiate addicts use the drug to detoxify from all opiates. Basically, it stops most withdrawal symptoms. It is also a bridge drug. They use it until they can obtain more opiates. If used more than two weeks, the addict has simply switched addictions - from opiates to Rohypnol. Habitual users will use anything to get a "fix", including Rohypnol. The most predominate user is the first-time, naive user. They are usually kids who are rebelling against their parents. Roche stated their studies show most of the kids could not pick out Rohypnol from the pill charts they were shown. The company expects to use the Haight Asbury to conduct research in the South Florida area. However they expect some drug connection. There will be few similarities between the Florida and Texas epidemics. The company has agreed to limit access to pharmacies in or near Mexican border towns. In South Texas, the Haight Asbury study determined there is no major syndicate involvement in the distribution of Rohypnol. The users go to a Mexican physician located near a pharmacy and obtain a prescription. They take it to the nearest full-service pharmacist and get the pills. Most orders are not over 100 pills and are easily hidden from Customs agents (who would not be concerned about a prescription drug from Mexico in the first place). The company states they do not conclusively know how it is currently entering the Florida region. Roche is negotiating with Mexican officials in an effort to regulate the Rophynol market. Their biggest concern is their lack of understanding the Mexican laws. The company fears any serious involvement with the Columbian government. They do no want their employees or investigators to die. My Thoughts on Rhynopol Roche used this as a meeting to prevent any further media damage or government action this drug. They are scared that Roche will be associated with the production of a "date-rape drug". I think they are willing to regulate themselves SO they can prevent damage control and government intervention. There were two cases in South Texas and Florida where the woman was raped after being exposed the Rohypnol. The kids call this violent activity, and getting high off the drug, as "roaching". The word Roche is printed on the tablet and the people mispronounce it. I have some serious misgivings about the validity and reliability of their research. First, they brought outsiders into South Texas to interview kids and users on the amount of the drug they used. Students are not generally honest about their use. They will lie to "look tough" or to cover up real usage amounts. While they did hire former users to interview them, these former users are outsiders to the South Texas. The interviewers are not familiar with the lifestyles and people. The interviewees will see them as "suckers" so they are more likely to lie than if it were someone they could identify with at the time. I asked the Roche representatives what were the other pills the users were shown. They all responded that various types were shown. Since generic forms of Rohypnol are just as easily available in Mexico as the Roche pill itself, I asked if they were pictured. There were no definitive answers. Furthermore, they stated they did not know if these users were taking the generic forms; yet, their findings in South Texas were conclusive. They did not know who the producers of the generic Rophynol market. Their only response was that 50 percent of men and 15 percent of the women could pick out the Roche pill. This made no sense to me and it was obvious I would get no further answers at this session. They were constantly referring to the drug as an oral drug. I asked them if their research showed that Rohypnol was smoked. Their studies did not show this occurrence at all. They stated the drug has no effect on the body once it is heated above 110 degrees. I stated the kids are still doing it and its use is increasing. When I called my friends in Phoenix, I learned some people crush the pill and mix it with marijuana. This is the second most common method of ingestion. The drug is not fatal unless the person ingests large amounts of alcohol and Rohypnol at the same time over a long period of time. Several people believe it is a loss leader by the black markets. They are attempting to gain more customers and they are targeting the three groups mentioned above. The Roche representatives stated they were the first company in American history to offer self-regulation to the government. They will work with the Mexican government to control the drug in border towns and foreign governments to prevent any leaks. They are also working with the Columbian government to prevent possible leaks from their country. The representatives agreed this would be difficult since the Columbian government is under siege. I agree. There was a brief mention of the product being shipped from other Central American or South American countries. No substantive investigations into this possibility were mentioned. This issue has become a race issue. Throughout 20th Century America, drug use has been a race issue. Opiate smoking was regulated in California because it was a Chinese tradition. The Chinese experienced racism throughout the region. No other opiate use was controlled. Marijuana and cocaine were regulated by state and local governments in an effort to control Hispanic and black populations. Once these problems involved white, middle-class Americans, federal involvement was demanded. When this was a South Florida/Caribbean problem, it was not a problem. When the drug entered Floridian, middle-class white American kids and young adults at dance bars, it became a problem. At this point in time, national citizen forces are not strongly aligned on this issue. Their influence at this time is not a factor in the policy making process. With media attention, this will grow without question. One salient, yet silent, factor in drug policy formulation is the alcohol and pharmaceutical industries. Tighter controls on these industries mean more money will be spent on drugs in the black market. Roche's meeting today falls along those lines. The only anomaly is Roche's advocating a mostly self-regulation measure. Roche is courting the Federal government in an effort to gain control of the situation without governmental action. In my opinion, it boils down to this - the Roche Company is afraid the American public will perceive this as the crack cocaine of the 1990s and the date rape pill. They gathered these groups of government employees together to encourage them to implement the company's wishes. My Recommendations Take no legislative action at this time. If the WH attempts to control Rohypnol, it must look at controlling other benzodiazepines like valium. After the Maxine Water's arguments on crack cocaine vs. cocaine sentencing, it would renew old arguments i.e., white middle-class VS. poor urban blacks, etc After further consideration, Senator Biden is more correct that I initially thought him to be. I still think a low-key approach to the problem is the Administration's best alternative. Media attention will increases youth demand for the drug. The country's best method to deter use is to deter youth attention while gaining the attention of community leaders such as school teachers, law enforcement agencies, and treatment facilities. If legislative means are necessary, Rohypnol should be given a Schedule 1 rating if treatment and educational funding is provided. I think this could resurrect Cong. Waters' arguments on cocaine and crack cocaine. If the Administration supports her statements, they can rely on a 1991 Minnesota case where the legal distinction between the two drugs and jail time was addressed. If no treatment funding is provided, the Federal government should list it as a Schedule 2 drug. Therefore, Federal, state and local governments could tax the drug and use the revenues for treatment and education initiatives. Used this way, Rohypnol could be the country's first controlled drug that viewes addiction as a public health problem rather than as a law enforcement one. Most opponents to this will cite this is a European measure and drugs are still prevelant in those countries. The argument can be counterattacked by stating the U.S. has the highest estimated addiction rates among all industrialized nations in the world. Furthermore, we have established this precedence in America with drug-addicted pregnant women. This statement will shut up the opposition. No one wants to publicly oppose children, particularly in an election year. The supply-siders, like Roche and William Bennett, will encourage punishment for possession of the drug. This may be a good offer. Unfortunately, these groups want to lock them up and throw away the key. The drug sellers serve one- third of their time and are released, due to jail overcrowding. This is a downside to listed Rohypnol as a Schedule 1 drug. Intensive treatment and educational funding must be provided to prevent the spread of this now "fad" drug. There is no mention in the Biden Report or with the ONDCP meeting of treatment funding for these addicted children. There is no mention of cooperation of cooperative efforts between state and local governments on this issue. - All action should originate from the Executive Branch. - Publicity should be avoided. Children watch television. If the media portrays this as the "crack of the 1990s", demand will increase. Many people will want to see what it is like and will try it. This could result in higher Rohypnol addiction rates than we are currently experiencing. The President should instruct the Secretary of State to contact his counterpart within the Mexican government. Since most of the South Texas business appears to be "mom- and-pop" store purchases in Mexico, the U.S. should encourage them to place stricter controls on the Rohypnol and its generic products in or near border towns. The President should instruct the Secretary of the Treasury to notify Customs agents of the increased use of this drug and it is made accessible through their ports of entry. Roach Pharmaceutical cited several instances where they asked people to purchase the drug and smuggle it over the border. Others were asked to declare it. In all cases, no action was taken by Customs. The President should instruct the Secretary of Health and Human Services to prepare a pamphlet for immediate distribution to all teachers, school administrators, treatment facilities, and emergency room personnel on this drug, its increased use among youth, and subsequent symptoms. Its use among habitual addicts should be mentioned as well. These groups are more likely to report is presence because of his involvement. Presidential attention to this issue will provide more reliable data available for study. Like the Secretary of State and HHS, the Attorney General should contact the appropriate agencies within her jurisdiction to control the spread of Rohypnol. Roche should be encouraged to apply for a patent on the drug. The only reason Rohpynol is not available on the American market today is due to its direct competition with valium. If they applied and received the rights to market the drug in the U.S., Roche could increase their profits on the drug by selling at a higher price in the United States than they would receive for Rohypnol in Mexico. The drug would be less alluring and the government could control its purity. The Federal government will monitor the drug. Rohypnol is not a drug like cocaine or heroin; therefore, it does not require a Schedule 1 rating. This will free the law enforcement agencies to monitor the influx of more serious drugs, like heroin and cocaine. - If this becomes the "Crack of the 1990s", executive action will prove to the American people during an election year that President Clinton has made every attempt to control this problem without media attention. Media attention could attract children to the drug, making all actions counterproductive. Thank you for the excellent opportunity. I want to participate in any and all of these opportunities that occur. Page 35 LEVEL 1 - 16 OF 29 STORIES Copyright 1995 The Tribune Co. Publishes The Tampa Tribune The Tampa Tribune September 12, 1995, Tuesday, FINAL EDITION SECTION: NATION/WORLD, Pg. 8 LENGTH: 508 words HEADLINE: What are kids doing out at 4 a.m.? BODY: It's 4 o' clock Sunday morning. Do you know where your kids are? That's the wake-up call that the parents of 2,500 mostly teenagers should have gotten this weekend when police and sheriff's deputies busted up a "rave" party in downtown Tampa. "Rave" clubs are the latest youth fad, drawing young people after bar closing hours to while away the morning dancing, lounging and generally having "fun." Within minutes of the bust at the Parthenon club, 13 people had been arrested - seven for possessing illegal drugs. Hundreds more appeared to be under the influence of something other than loud music. The smell of cigarettes, marijuana and alcohol hung in the air. Police confiscated LSD, marijuana, ecstasy and Rohypnol. LSD, as nearly everyone knows, is a hallucinogenic drug popular during the '60s and currently experiencing a revival. Ecstasy is a powerful and very addictive drug that has been available for years. And, Rohypnol is one of the newer drugs on the underground market. A sedative similar to Halcion and Valium, it mimics alcohol intoxication. Nicknamed "roofies," the pills sell for $ 3 to $ 5 each and are growing in popularity. Rohypnol is the drug Broward County prosecutors say a rapist used earlier this year to sedate women he met in bars and later attacked. No responsible parent would want a son or daughter trying these dangerous drugs. But one has to wonder how many of these kids have responsible parents. Among those arrested were 17-year-olds from Tampa, Pinellas Park and St. Petersburg. Police suspect others in the crowd were 16, 15 and possibly even 14. Party-goers interviewed by The Tampa Tribune said they've seen children as young as 12 at some "rave" parties. Hellooooo. Is an adult present at these kids' homes? Tampa has a curfew that was supposed to put an end to such shenanigans, but TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 36 The Tampa Tribune, September 12, 1995 everyone knows it is largely ignored. City officials say they are sitting helplessly on their hands until some high court somewhere says curfews are legal. So much for bold leadership. Courts haven't stopped cities like Phoenix, Washington, D.C., Atlanta, Boston, Buffalo, Dallas, Denver, New Orleans, Newark and Orlando from adopting and enforcing curfews. Indeed, those cities have seen a significant drop in juvenile crimes such as auto thefts ever since the kids were forced to stay off the streets in the middle of the night. Parents who can't see to it that their kids get home by midnight or shortly after don't get a lot of sympathy here. Certainly parenting is hard work. Saying no, being firm, taking away the car keys isn't easy. But it has to be done to assure the kids' survival. As for the dance clubs that put on the "raves," the police are well within their jurisdiction to do just what they did at Parthenon over the weekend: shut them down. Police cited faulty wiring and unsafe conditions in order to close the place. They can also go a step further and declare them a public nuisance. This community doesn't need a business that entices kids to stay out all night. TYPE: EDITORIAL; EDITORIALS LOAD-DATE: September 14, 1995 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier pic group Page 37 LEVEL 1 - 17 OF 29 STORIES Copyright 1995 TEXAS MONTHLY, INC. TEXAS MONTHLY September, 1995 SECTION: STATE WIDE REPORTER; Pg. 88 LENGTH: 839 words HEADLINE: A New Low BYLINE: HELEN THORPE; Edited by David McCormick HIGHLIGHT: Across the state, kids are getting seriously messed up on a dirt-cheap downer from Mexico. BODY: ROB IS A JITTERY NINE-teen-year-old bean pole who lives in Houston. He doesn't work or go to school, but he spends a lot of time in the city's nightclubs, where he frequently buys a potent sedative called Rohypnol. A single two-milligram pill has more intoxicating power than a six-pack of beer. "I was at Numbers, a club down the street," says Rob, sitting in front of a youth center on Westheimer. "I took two Rohypnol and I was like he rolls his eyes, tilts his head, and lets his tongue hang out of his mouth. "I went outside and there were these two cops in the parking lot. I said, 'Excuse me, Mr. Beers, I haven't had any officers tonight. Although Rohypnol is illegal in the United States, it is available by prescription in Mexico, and importing it is no trouble at all: Lately the drug has become a fad among teenagers around the state. Rohypnol is manufactured by the Swiss pharmaceutical giant Hoffman-La Roche and was introduced in the seventies in Europe and South America, where it is prescribed as a means to relax patients before surgery and as a treatment for insomnia. Beginning in the eighties, hard-core drug users in Europe started using it to come down from cocaine or metham-phetamine highs. Now thrill-seeking teenagers in Texas, Florida, and other parts of the South have discovered the drug. To them, it's ideal because it makes them feel drunk but doesn't make them throw up, doesn't show up in the most common urine tests, and is dirt cheap. One pill can cost anywhere from $ 1 to $ 5. But the pills are far from harmless; early last year, the late grunge rock star Kurt Cobain slipped into a coma after taking Rohypnol and drinking champagne while on tour in Italy, though he was revived after his stomach was pumped. So many teenagers have been taking it that the Texas Commission on Alcohol and Drug Abuse (TCADA) issued a warning to drug treatment centers about the pills in May. On the street the drug has many nicknames; teenagers know it as rope, ribs, or roaches. Law-enforcement authorities call it Mexican Valium because of its similarities to that drug, but Rohypnol is estimated to be ten times stronger and has some novel attributes. Another of its many names is "the forget pill,' because Rohypnol typically causes complete short-term amnesia. It also reduces inhibitions. Rob says, "You take it -- you black out. The next day TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 38 TEXAS MONTHLY September, 1995 people tell you what you did, and you're like, 'Wha-a-a-a-t?"" In rare cases Rohypnol can also induce aggression, rages, hallucinations, or psychoses. Many teenagers take it while drinking, which greatly increases the impairment of their motor abilities. Statewide, there have been two suspected fatal overdoses. Rohypnol first became popular in border towns. According to figures compiled by the TCADA, law enforcement along the border reported 31 cases involving the drug in 1991. Last year there were 197 cases. Nilda Gomez, a drug abuse counselor who works with teenagers in Brownsville, says Rohypnol is everywhere she turns. "What's so surprising is that it used to be fifteen-year-olds who were doing drugs, but now it's thirteen-, twelve- and even eleven-year-olds,' " says Gomez. The use of Rohypnol gradually spread north, and today drug counselors in Houston, San Antonio, Dallas, and Austin know of people who have taken Rohypnol. The drug is said to have a moderate to high risk of addiction. Eight months ago Annette, a self-possessed sixteen-year-old, was buying Rohypnol regularly in clubs along Sixth Street in Austin. (Her name has been changed to protect her privacy.) She now lives in Odyssey House, a residential treatment facility in Houston for teenagers. As she sits on a sofa there, wearing a white T-shirt and white cotton pants, her honey-colored hair twisted into a bun, Annette looks like an extra in Beverly Hills 90210. but she recites a family history of abuse and chemical dependency. "I'm the kind of person who wouldn't take one or two," she says of her experiences with Rohypnol. "I would take three or four and drink at the same time. We used to call them 'run-trip-and-falls. Sometime last year Annette took enough Rohypnol to obliterate four full days. She came to at her boyfriend's house, with a hospital band around her wrist. "A friend of mine from San Antonio had run away, and she wanted to do some because she'd never tried them. We got a lot. The last thing I remember is my friend turning to me and saying, 'Annette, we need to go. And then it just goes black. "Four days later I woke up well, not really woke up, because I hadn't been asleep. I had gone to another friend's apartment, and I had had sex with somebody this is what they told me and I had had a tampon in, and it had gotten stuck up inside me, so I had to go to the emergency room. I lost track of my friend, and she didn't know anybody in Austin.' Clearly, playing drugstore cowboy is no game. Rohypnol is more than an easy way to get wasted it's an easy way to waste a life. GRAPHIC: Picture, Known as "the forgot pill, "-Rohypnol reduces inhibitions and causes short-term amnesia. ANDREW YATES LANGUAGE: ENGLISH TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 39 LEVEL 1 - 18 OF 29 STORIES Copyright 1995 The Tribune Co. Publishes The Tampa Tribune The Tampa Tribune June 23, 1995, Friday, FINAL EDITION SECTION: FLORIDA/METRO, Pg. 6 LENGTH: 359 words HEADLINE: Radio host blamed for drug mishap BYLINE: WILLIAM YELVERTON; Tribune Staff Writer DATELINE: CLEARWATER BODY: Prosecutors are holding radio personality Ron Bennington of "Ron and Ron" fame responsible for leaving an illegal drug where his young daughter could find it. The 10-year-old girl was hospitalized overnight in March. She fell asleep and couldn't be roused after taking medicine from a box marked "children's Tylenol." An investigation determined the child had taken an undetermined amount of Rohypnol - a powerful narcotic similar to Valium - that was in the Tylenol container. Pinellas sheriff's spokeswoman Marianne Pasha said Bennington told a deputy someone in Miami had given him the Rohypnol a year ago. His daughter was taken to All Children's Hospital in St. Petersburg for observation but was home the next day, Pasha said. "Ron felt very bad about the whole situation," Pasha said. Bennington, 36, who with Ron Diaz has a popular show on WSUN, was charged earlier this month with culpable negligence in the March 6 incident at his Seminole home. He has filed a written plea of not guilty. Bennington agreed to enter a pretrial intervention program, said Rebecca Graham, assistant county court director for Pinellas State Attorney Bernie McCabe. The program is a form of probation for first-time, nonviolent offenders. If participants complete the program and stay out of trouble, charges are dropped. Bennington could not be reached for comment Thursday. His daughter, Gail, was taken to a Seminole hospital the night of March 6 after her mother couldn't rouse her, Pasha said. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier pk group Page 40 The Tampa Tribune, June 23, 1995 Julie Bennington told a deputy who was called to the hospital that she feared the girl was having an allergic reaction to children's Tylenol. The mother had told the girl to take the Tylenol earlier that night when she wasn't feeling well. At the request of emergency workers at the hospital, Julie Bennington telephoned her husband and told him to bring in the box and package, Pasha said. Ron Bennington was charged June 8. He was not arrested. Instead he was issued a summons. His wife was not charged. Although Rohypnol, also known as "roofies," "rufies" and Roche, is illegal, Bennington was not charged with a drug offense. GRAPHIC: PHOTO, Ron Bennington TYPE: FOCUS ON FLORIDA LOAD-DATE: July 3, 1995 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier pk group Page 41 LEVEL 1 - 19 OF 29 STORIES Copyright 1995 The Dallas Morning News THE DALLAS MORNING NEWS June 15, 1995, Thursday, HOME FINAL EDITION SECTION: NEWS; Pg. 1A LENGTH: 1065 words HEADLINE: Dangerous sedative being smuggled across border Mind-altering drug reduces inhibitions, can cause amnesia BYLINE: Rebecca Howland, Staff Writer of The Dallas Morning News BODY: Law enforcement officials say they are alarmed at the growing popularity of a dangerous and potent sedative being smuggled across the Mexican border and now making its way north through the state. Rohypnol - commonly called Roach, Rophie or the Forget Pill on the street - is a hypnotic or mind-altering drug that reduces users' inhibitions and can cause amnesia, especially when taken with alcohol. The drug reportedly has been used in gang initiations and date-rape cases in which the woman can't remember the next day what happened, say drug treatment and law enforcement officials. The drug - which officials say is about 10 times stronger than Valium - is illegal in the United States. But in other countries anyone can get Rohypnol with a doctor's approval, and in some, including Mexico and Colombia, it is often sold over the counter. The drug is most often seen among males ages 13 to 18 and is frequently used in gang initiations, officials in South Texas say. Law enforcement officials and medical experts say use of the drug in South Texas is skyrocketing, and there is increasing incidence of it in Austin, Houston and Dallas. The drug is often sold on the street for 50 cents to $ 3 a pill, officials said. Use of the drug has also increased dramatically in southern Florida, especially in Miami, since 1992. Officials there said it is streaming into the United States from Colombia. Hoffmann-LaRoche, a Switzerland-based pharmaceutical company that manufactures the drug, produces Rohypnol in plants in Colombia and Mexico. Although selling Rohypnol over the counter is technically illegal worldwide, it happens frequently in the two countries, which do not effectively enforce regulations, officials from the World Health Organization said. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier pk group A member of the Reed Elsevier plc group A member of the Reed Elsevier pk group Page 42 THE DALLAS MORNING NEWS, June 15, 1995 The drug is used as a sleeping aid to combat severe insomnia or to sedate psychotic patients, said Al Wasilewski, director of public policy and communications for Hoffmann-LaRoche. It is also prescribed to patients about to undergo surgery and who are not going to receive full anesthesia. After taking the drug, the patient would not remember the uncomfortable procedure. Mr. Wasilewski declined to comment about whether or not Hoffmann-LaRoche would consider discontinuing its production of the drug, although he said the company is "very concerned" about the abuse. Rohypnol "happens to have that attraction to a certain subset of the population that will abuse anything It is an unbelievable thing to hear that these drugs which have a good therapeutic use are being abused in this way, If Mr. Wasilewski said. Hoffmann-LaRoche never sought approval from the Food and Drug Administration to distribute Rohypnol in the United States, he said. "There was already a significant number of similar sedative hypnotics" in the United States, he said. "There was no need to add another one to the pie." Steve Mithos, the director of program services for the Palmer Drug Abuse treatment center in McAllen, said more than half of the teenagers he sees are "getting roached." "It's pretty widespread, and in the last six months, it's really grown, " he said. "Now, about 15 percent of the kids I see list it as their primary drug of choice, not just something they take once in a while." Sean, a 19-year-old in treatment for drug abuse in Dallas and who asked not to be identified by his last name, said Rohypnol began "hitting it big" on Dallas' club and party scene last year. Sean estimated that half of his friends had experimented with the drug or were using it regularly. "It's everywhere," he said. "If you just go down and see a doctor in Mexico and get a prescription, you can carry five boxes across the border, no problem, " he said. "Each box has 50 or 100 pills in it." " Sean estimated he'd taken the pills 10 or 11 times. "It's real mellow. I just felt like I didn't want to move, " he said. Although Sean described feeling "under control" while on the drug, he recounted experiencing amnesia after mixing the drug with alcohol, and described several "incidents" in which men "took advantage of women sexually because the women didn't know what they were doing." " The drug can also trigger belligerent and aggressive behavior, Mr. Mithos said. One of Mr. Mithos' patients is on probation for manslaughter, he said. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 43 THE DALLAS MORNING NEWS, June 15, 1995 "The guy doesn't even remember shooting anyone. He's neat, a real nice guy. You wouldn't think he would do something like that, but he was loaded on Roaches. If In Austin and Houston, law enforcement officials say the drug is rapidly growing in popularity and is most often seen in conjunction with "heavier" drugs such as heroin or crack cocaine. "We're seeing (Rohypnol) all over the place," " said Tony Arnold, a forensic chemist for the Austin Police Department. "People are using the hyperactive drugs, and when they finally burn out, then they use the Rohypnol to go to sleep, Mr. Arnold said, estimating that one out of every five cases he sees involves the drug. A few months ago, nobody had heard of the drug, Mr. Arnold said. "At first, most of the cops thought they were 2-milligram Valiums, he said. Hoffmann-LaRoche also produces Valium, a small, blue pill stamped with the number "10" in a circle. Rohypnol differs in color - it is white - and is marked by "2" instead of "10." The numbers refer to the dosage of the active ingredient in milligrams. Many law enforcement officials in Dallas said that while they had encountered the small white pills several times during the past year, they were not overly concerned that it was getting out of control. But Martin Pracht, who works for the Drug Enforcement Administration in Dallas, said officials are underestimating the drug's spread. "Rophies are much more dangerous and potent than what people are giving them credit for, Mr. Pracht said. "You'd be crazy to say this will not be a problem" in Dallas. "It's just taking a while to get up here and increase in popularity. But it will," he said. Because the drug has never been legal in the United States, detecting it is difficult, Mr. Pracht said. The drug is not listed in the commonly-used Physician's Desk Reference, and police and medical officers do not know what symptoms to look for. Customs officials on the border said it is difficult to stop such smuggling because officers search for materials that look like contraband. GRAPHIC: CHART (S) (DMN) Rohypnol. LANGUAGE: ENGLISH LOAD-DATE: July 13, 1995 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A inember of the Reed Elsevier plc group Page 44 LEVEL 1 - 21 OF 29 STORIES Copyright 1994 The Atlanta Constitution The Atlanta Journal and Constitution November 29, 1994 SECTION: NATIONAL NEWS; Section D; Page 17 LENGTH: 256 words HEADLINE: 'Roofies' give Florida teens a cheap high Popular drug makes its users feel drunk BYLINE: By Donna Pazdera FORT LAUDERDALE SUN-SENTINEL BODY: Fort Lauderdale, Fla. - It's just a $ 5 hit. But wash it down with a beer and you might do something embarrassing - or downright scary. You might crumple to the ground. Or urinate on yourself. Or stop breathing. Technically, the drug is called Rohypnol. Those more familiar with the little white pills call them "roofies." If you haven't heard of them yet, you will, drug abuse specialists and police say. "It will be as popular as crack because it is so cheap," said Dave Marcus, case manager at Spectrum Program Inc., a drug treatment center for adolescents in Pompano Beach, Fla. High schoolers are particularly fond of roofies because they are cheap and because they make them feel very, very drunk, Marcus said. The pills sell for $ 3 to $ 5 apiece. Teenagers generally buy the drug off-campus and take it at weekend parties. Sometimes they pop one in the morning before school, making them incoherent all day. "It's like the poor man's Quaalude, " Marcus said, referring to a sedative drug that was popular in the 1970s. It's not known how many people are abusing Rohypnol, but in Broward County, Fla., nearly one in five clients at two drug treatment centers for adolescents have used them. In Palm Beach County, Fla., officials say roofies are slowly becoming popular with teenagers and young adults. Rohypnol, manufactured by Roche, a U.S. pharmaceutical company, is not legal in the United States. It is used in Central and South America to sedate patients for surgery, said Al Wazaluski, a Roche spokesman. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 45 1994 The Atlanta Journal and Constitution, November 29, 1994 LANGUAGE: ENGLISH LOAD-DATE: December 1, 1994 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group R A member of the Reed Elsevier plc group R A member of the Reed Elsevier pk group Page 44 LEVEL 1 - 21 OF 29 STORIES Copyright 1994 The Atlanta Constitution The Atlanta Journal and Constitution November 29, 1994 SECTION: NATIONAL NEWS; Section D; Page 17 LENGTH: 256 words HEADLINE: 'Roofies' give Florida teens a cheap high Popular drug makes its users feel drunk BYLINE: By Donna Pazdera FORT LAUDERDALE SUN-SENTINEL BODY: Fort Lauderdale, Fla. - It's just a $ 5 hit. But wash it down with a beer and you might do something embarrassing - or downright scary. You might crumple to the ground. Or urinate on yourself. Or stop breathing. Technically, the drug is called Rohypnol. Those more familiar with the little white pills call them "roofies. " If you haven't heard of them yet, you will, drug abuse specialists and police say. "It will be as popular as crack because it is so cheap," said Dave Marcus, case manager at Spectrum Program Inc., a drug treatment center for adolescents in Pompano Beach, Fla. High schoolers are particularly fond of roofies because they are cheap and because they make them feel very, very drunk, Marcus said. The pills sell for $ 3 to $ 5 apiece. Teenagers generally buy the drug off-campus and take it at weekend parties. Sometimes they pop one in the morning before school, making them incoherent all day. "It's like the poor man's Quaalude,' Marcus said, referring to a sedative drug that was popular in the 1970s. It's not known how many people are abusing Rohypnol, but in Broward County, Fla., nearly one in five clients at two drug treatment centers for adolescents have used them. In Palm Beach County, Fla., officials say roofies are slowly becoming popular with teenagers and young adults. Rohypnol, manufactured by Roche, a U.S. pharmaceutical company, is not legal in the United States. It is used in Central and South America to sedate patients for surgery, said Al Wazaluski, a Roche spokesman. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier pk group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 45 1994 The Atlanta Journal and Constitution, November 29, 1994 LANGUAGE: ENGLISH LOAD-DATE: December 1, 1994 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS R A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group R A member of the Reed Elsevier plc group Page 46 LEVEL 1 - 22 OF 29 STORIES Times Publishing Company St. Petersburg Times November 29, 1994, Tuesday, Tampa Edition SECTION: TAMPA TODAY; TAMPA BAY & STATE; Pg. 5B DISTRIBUTION: TAMPA TODAY; TAMPA BAY AND STATE LENGTH: 511 words HEADLINE: Tranquilizer hooks teens, drug users BYLINE: SUSAN CLARY BODY: It's just a few dollars a hit. But wash it down with a beer and you might do something embarrassing - or downright scary. You might crumple to the ground. Or urinate on yourself. Or stop breathing. Technically, the drug is called Rohypnol. Those more familiar with the little, white pills call them "Roofies." If you haven't heard of them yet, you will, drug abuse specialists and police say. "They have become the Quaaludes of the '90s," said Dr. Sven Norman, referring to a sedative that was popular in the 1970s. "One of the reasons they are abusing it is they get the desired effect. It causes drowsiness and a pretty significant intoxication." Norman, director of the Florida Poison Information Center at Tampa General Hospital, said the center first heard of the drug earlier this year. Experts say it is popular with three groups. Teenagers use it to intensify the effects of alcohol. Heroin users like it because it enhances the sedating effects of lower-purity heroin. Cocaine abusers use it to parachute down from a binge. "It is extremely dangerous," Norman said. "When combined with alcohol, it can be life-threatening." The tranquilizer is a small, white tablet imprinted with the letters RH. Experts say the drug is several times more powerful than Valium. Users call the pills "roofies," "ruffies" or "Roche," (pronounced Ro-shay) after the company that makes them. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier pic group Page 47 St. Petersburg Times, November 29, 1994 The drug's side effects include hallucinations, respiratory problems, sleep disturbances and anxiety. While the drug is widely used in South Florida, law enforcement officials in the Tampa Bay area said they have yet to see any cases. "I'm not saying it doesn't exist around here, but it's not a problem. Not yet," said Lt. Bob Guidara, commander of the Tampa Police Department QUAD Squad. St. Petersburg police spokesman Bill Doniel said the same is true in his city but noted that new drugs in South Florida often migrate here. Roofies have become especially popular with high schoolers because they are inexpensive - 50 cents to $ 8 each. When taken alone, they make users feel very sleepy. The effect is intensified when combined with alcohol. Rohypnol is manufactured by Roche, a U.S. pharmaceutical company, but is not legal here. It is used in Central and South America to sedate patients for surgery, said Al Wazaluski, a Roche spokesman. - Information from the Associated Press was used in this report. TEEN DRUG NAME: Rohypnol (Roofies) WHAT IT LOOKS LIKE: Little white pills. PRICE: Inexpensive - $ 3 to $ 5 each. WHAT IT DOES: Used alone, roofies make users feel very sleepy. Combined with alcohol, the effect intensifies. Described as 10 times stronger than Valium. Side effects include hallucinations, respiratory problems, sleep disturbances, anxiety and possible addiction. MANUFACTURER: Rohypnol is manufactured by Roche, a U.S. company, but is not legal here. Authorities think the drug is being brought in from South America. LANGUAGE: ENGLISH LOAD-DATE: November 30, 1994 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 48 LEVEL 1 - 23 OF 29 STORIES Copyright 1994 Phoenix Newspapers, Inc. THE PHOENIX GAZETTE November 29, 1994 Tuesday, Final SECTION: FRONT; Pg. A2 LENGTH: 351 words HEADLINE: NEW, CHEAP DRUG CATCHING ON WITH TEENS DATELINE: FORT LAUDERDALE BODY: It's just a $5 hit. But wash it down with a beer and you might do something embarrassing or downright scary. You might crumple to the ground. Or urinate on yourself. Or stop breathing. Technically, the drug is called Rohypnol. Those more familiar with the little white pills call them roofies. If you haven't heard of them yet, you will, drug abuse specialists and police say. "It will be as popular as crack because it is so cheap," said Dave Marcus, case manager at Spectrum Program Inc., a drug treatment center for adolescents in Pompano Beach, Fla. In Arizona, however, the drug is unknown, police said. "We've never even heard of it, but if it gets popular in other areas of the country, it will get here sooner or later,' said Lt. Rick Knight, a state Department of Corrections narcotics detective. High schoolers are particularly fond of roofies because they are cheap and because they make users feel very, very drunk, Marcus said. The pills sell for $3 to $5 apiece. Teenagers generally buy the drug off-campus and take it at weekend parties. Sometimes they pop one in the morning before school, making them incoherent all day. "It's like the poor man's Quaalude," Marcus said, referring to a sedative drug that was popular in the '70s. It's not known how many people are abusing Rohypnol, but in Broward County, Fla., nearly one in five clients at two drug treatment centers for adolescents have used them. Rohypnol is manufactured by Roche, a U.S. pharmaceutical company. The drug is TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier pk group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 49 THE PHOENIX GAZETTE, November 29, 1994 not legal in the United States. It is used in Central and South America to sedate patients for surgery, Al Wazaluski, a Roche spokesman, said. School officials say many teenagers get the drug at parties, where it is given away by a dealer who is looking for customers. The drug, sold in tablet form, has been described as 10 times stronger than Valium. Used alone, roofies make users feel very sleepy. Combined with beer, the effect is intensified. The drug also is crushed and snorted to cushion the crash from a cocaine or crack high, said Hollywood Police Sgt. Mark May. LANGUAGE: ENGLISH LOAD-DATE: December 13, 1994 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier pic group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 28 LEVEL 1 - 13 OF 29 STORIES Copyright 1995 Star Tribune Star Tribune October 24, 1995, Metro Edition SECTION: Variety; Pg. 1E LENGTH: 538 words HEADLINE: FYI; Kissing Keanu and telling BODY: Noting that after 25 takes of a kissing scene with Keanu Reeves for "Bram Stoker's Dracula, " Winona Ryder "reportedly left the set in tears, II YM (Young and Modern) magazine has harvested the following smooching critiques: "Keanu's so sure of himself, but I was back there spraying Binaca and hoping that I wouldn't offend him. " - Sandra Bullock, costar in "Speed." "He was pretty scruffy but he had a sexy smell. " - Ione Skye, costar in "River's Edge. " "Kissing scenes are pretty complicated, but we tried to enjoy them. " - Aitana Sanchez-Gijon, costar in "A Walk in the Clouds. " "He's a very good kisser. He's definitely blessed. II - Lori Petty, costar in "Point Break. " - San Francisco Chronicle 'Spanish fly' becomes real Rohypnol, an illicit sedative-hypnotic drug most commonly abused in Florida and Texas, has made its way to Minnesota. It is used for medicinal purposes in other parts of the world, but not approved in the United States. Primary users are adolescents who combine it with alcohol and other drugs. Because of its amnesialike effects, it is also being used as a "date rape" drug, according to a drug alert issued by Carol Falkowski, research coordinator for the Chemical Dependency Division of the Minnesota Department of Human Services. In southern Minnesota, abuse of the drug has been suspected in several cases in which a drug was placed in alcoholic beverages of young females who are subsequently exploited sexually, said Falkowski. Victims have no recall of events following sedation. Rohypnol has a bitter taste when added to a beverage and is about 10 times more potent than Valium. For more information on TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier pk group Page 29 Star Tribune, October 24, 1995 Rohypnol, call the Minnesota Prevention Resource Center at (800) 247-1303. - Hazelden Foundation Today Costumed guides will lead visitors by candlelight through Historic Fort Snelling. The living-history players will be preparing for winter. When: 7 to 9 p.m. today Where: Historic Fort Snelling, Hwy. 5 and 55, near the Minneapolis-St. Paul International Airport. Admission: Adults, $ 6; seniors, $ 5; ages 6 to 15, $ 4. Call: 725-2413 Same space, whole new place The old Rupert's in Golden Valley has been remodeled and reincarnated as the Metropolitan, an elegant room to rent for events and concerts. The Metropolitan, on Interstate Hwy. 394, is owned by upscale Twin Cities restaurateurs, the D'Amico Brothers. The space underwent a $ 1 million renovation. It seats 730 people for concerts at tables on various tiers. A site for wedding and bar mitzvah parties, it also will be open to the public for the "Live at the Met" concert series in the next few weeks. October Project, an arty pop band featuring poetic singer Mary Fahl, will kick off the series tonight. Lowen & Navarro, an adult-pop duo, will do the Met Nov. 21, and jazz vocalist Dee Dee Bridgewater will sing there Nov. 26. What: October Project. When: 8 p.m. today. Where: The Metropolitan, 5418 Wayzata, Blvd., Golden Valley. Admission: $ 14 to $ 20. Call: 989-5151. - TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group R A member of the Reed Elsevier pk group Page 30 Star Tribune, October 24, 1995 GRAPHIC: Photograph LANGUAGE: ENGLISH LOAD-DATE: October 25, 1995 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 31 LEVEL 1 - 14 OF 29 STORIES Copyright 1995 Sentinel Communications Co. THE ORLANDO SENTINEL October 3, 1995 Tuesday, METRO SECTION: LOCAL & STATE; Pg. C5 LENGTH: 494 words HEADLINE: ST. CLOUD MAN DIES FROM ILLEGAL DRUG; POLICE SAID THE 20-YEAR-OLD OVERDOSED ON THE ILLEGAL SEDATIVE SMUGGLED FROM SOUTH AMERICA. BYLINE: By Henry Pierson Curtis of The Sentinel Staff DATELINE: KISSIMMEE BODY: A St. Cloud man may be one of the first victims in Florida to die from an overdose of an illegal sedative smuggled from South America. Stacy McCormack died sometime Sunday after swallowing more than a dozen tablets of Rohypnol, a drug commonly called "roofies," Kissimmee police said. The sedative is 10 times more powerful than Valium and is becoming known as the "Quaalude of the '90s," a reference to the drug widely abused in the 1970s. Rohypnol has become increasingly popular in the past few years among high school students mixing it with beer for a cheap high, drug abuse authorities said Monday. Spokesmen for the Florida Poison Information Centers said Monday that no Rohypnol-related deaths had been reported previously to offices in Miami, Tampa and Jacksonville. It's possible that previous fatalities have not been reported by medical examiners to the statewide network, they said. "We've just been lucky that kids who take it are just slumped over their desks in school and not driving. It's just a matter of time (until) we're going to have a couple, " said Dr. Susan Sandbeck, deputy director of the Florida Poison Information Center in Miami. "It's fast acting; it's intense. It's a great buzz but all you have to do is get a kid who vomits or get a kid who is driving a car and it's deadly." McCormack, 20, was found dead about 10:30 p.m. Sunday on a couch in a friend's apartment on Central Avenue in Kissimmee. He had gone to sleep about 7 a.m. after taking "roofies" and watching movies, Kissimmee police Detective Warren Shepard said. McCormack, who worked construction and had been in robust health, apparently choked on his own vomit after falling asleep, police reported. Several of his friends told police that McCormack began taking Rohypnol several months ago and had taken as many as 14 tablets at one time. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier pic group A member of the Reed Elsevier pk group Page 32 Orlando Sentinel Tribune, October 3, 1995 The Orange-Osceola Medical Examiner's Office said the cause of McCormack's death will not be known for several weeks - until toxicology tests are completed. The office is investigating a second possible Rohypnol-related death, a spokeswoman said. The victim of that overdose was a Brevard County woman who died last week in an Orlando-area motel room. Additional information about the death could not be obtained Monday from the Orange County Sheriff's Office. Rohypnol is the brand name of flunitrazepan, a sedative sold in Europe, South America and Asia by Roche, a Swiss pharmaceutical company. Its sedation lasts about an hour and it is used to calm patients for minor surgery in physicians' offices, pharmacists said. In interviews Monday, several people said Rohypnol sells for $5 a tablet in Orlando-area nightclubs. Authorities said it began appearing in mid-1989 in South Florida and that most shipments appear to come from Colombia. Rohypnol abuse can cause hallucinations, slowed reflexes and altered depth perception. Overdoses can cause respiratory arrest or death from aspirating vomit. LANGUAGE: ENGLISH LOAD-DATE: October 4, 1995 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 50 LEVEL 1 - 26 OF 29 STORIES Copyright 1994 South China Morning Post Ltd. South China Morning Post June 3, 1994 SECTION: NEWS; Pg. 7 LENGTH: 1120 words HEADLINE: Doctor in the clear over drug accusation BYLINE: By STEVE BALL BODY: A DOCTOR who, after a barely two-minute consultation, sold an addictive drug demanded by a patient he had never seen before was last night cleared of professional misconduct by the Medical Council. Dr Yu Hon-biu supplied 10 tablets of the tranquilliser Rohypnol to an undercover policewoman on July 27, 1990, almost without question, the Medical Council heard. But the council decided the evidence against Dr Yu was not sufficient to prove a charge of misconduct in supplying the drug. Dr Yu said may have been slightly negligent'', but that was not the same as misconduct. Rohypnol, chemical name Flunitrazepam, is a commonly abused drug and, since October 7, 1990, has been listed as a dangerous drug. But Dr Yu denied the drug was addictive. ''It is not a drug of dependency, he told the council. Dr Yu based his knowledge mainly on a book written before Rohypnol was invented. He came to the council with his copy of the third edition of Goodman and Gilman's Pharmacological Basis of Therapeutics, published in 1965, while Dr Yu was at medical school. Council chairman Professor Rosie Young Tse-tse pointed out that the book was almost 30 years old. Dr Yu said: 'But what was written there was facts. In 1965, Professor Young said. 'Still facts, replied Dr Yu, who graduated in 1968. In his final submission to the council, Dr Yu put his hand on his Goodman and Gilman's and said: ''If you say that is not the authority then I don't have any more to submit. Professor Young pointed to a passage in the Eighth edition of Goodman and Gilman's, published in 1990, which warned that tranquillisers were potentially TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Recd Elsevier plc group A member of the Reed Elsevier pk group Page 51 South China Morning Post, June 3, 1994 addictive with unpleasant and sometimes dangerous side effects. The council heard that at around 4 pm on July 27, 1990, police constable Yeung Miu-hung went to Dr Yu's surgery in Ferry Street, Kowloon, and said: ''I want Rohypnol . It was Ms Yeung's first visit to the clinic, but Dr Yu did not ask her about her previous medical history. Instead, he simply asked her 'Insomnia?' Ms Yeung replied ''Yes'', and she told the council Dr Yu then stared at her in such a way as if to suggest: 'How many tablets would you like?' She asked for 10 and Dr Yu charged her $ 4 for each tablet. There was no charge for the consultation. Dr Yu did not tell Ms Yeung how the tablets should be taken. He did not write out a prescription and the tablets were supplied separately by the clinic nurse, who was not a registered nurse, based on Dr Yu's patient notes. Cross-examining, Senior Crown Counsel Lynda Shine said: ''As a professional doctor you did not know anything about this patient's medical history. ' Dr Yu agreed, but objected when Ms Shine said his conduct had been 'cursory and unprofessional' and the drug prescription had not been bona fide. Dr Yu said he did not need to ask any more questions. 'She said she was an insomniac, that was enough. Council member Dr David Fang then asked Dr Yu if there could have been any other reason for lack of sleep other than insomnia. Dr Fang said: For instance, she might have had a brain tumour. 1 Dr Yu did not answer that question, but later said: did not know of any organic cause of insomnia. During the hearing, Dr Yu frequently referred to the drug manufacturers' leaflet on Rohypnol as evidence of the drug's effectiveness for all types of insomnia. The leaflet said that it was not advisable to prescribe the drug for someone who was in the first stages of pregnancy. Dr Yu admitted that he did not ask Ms Yeung whether she was pregnant. LANGUAGE: ENGLISH LOAD-DATE: June 15, 1994 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 26 LEVEL 1 - 12 OF 29 STORIES Copyright 1995 The Scotsman Publications Ltd. The Scotsman November 14, 1995, Tuesday SECTION: Pg. 2 LENGTH: 1960 words HEADLINE: Fresh drug menace surfaces BYLINE: Severin Carrell Home Affairs Correspondent BODY: FEARS are growing that a potent sleeping tablet blamed for drug deaths in Europe and the United States may be replacing temazepam among users and addicts in Scotland. Drugs agencies and police have received reports that heroin addicts and regular drugs users in Greenock, Glasgow, Dundee and Stirling have begun abusing Rohypnol, a strong sedative used mainly for insomnia, in conjunction with other substances and alcohol. Batches of the drug, known to users as Wallbangers or Roofies, have been seized by Strathclyde police for the first time. About 2000 have been impounded in two recent hauls. One English force has also begun investigating counterfeit Rohypnol imports. Rohypnol has caused controversy in the Netherlands, Germany, and the US over drugs deaths, illness due to breathing problems and acts of violence by users who had taken the stronger, two-milligramme tablet which is sold in Europe. One of the world's largest pharmaceutical firms, Roche, has voluntarily stopped making the stronger tablet and replaced it with much lower dosage, one- milligramme pills similar to those sold in the United Kingdom. Dr Donald Uges, a specialist in forensic toxicology and drug analysis from Groningen in Holland, said the drug became popular among Dutch football hooligans as it promoted aggression and among drug addict prostitutes as it sedated them before sex. Heroin addicts take it to boost the effects of poor quality heroin, and cocaine users use it to smooth out withdrawal. He added doctors and drug addicts had stopped using or dispensing the drug recently because it was SO dangerous if taken with other drugs or alcohol. "You won't be happy when Rohypnol is in your country, II Dr Uges told The Scotsman yesterday. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 27 The Scotsman, November 14, 1995 "Rohypnol is even worse and more dangerous than temazepam." The drug was withdrawn from National Health Service lists in 1985 after the Government began its "selected list" of the cheapest generic drugs. But its use in private prescriptions has remained high, with boxes of 30 costing pharmacists £ 4.08. Rusty Murray, chair of a voluntary drug users group in Dundee, said he knew of about 20 to 30 addicts and users in the city who took Rohypnol regularly, plus others in areas of Glasgow. They acquired purple, diamond-scored, one-milligramme pills from doctors by buying them on private prescription, took them personally or sold them off to other users or dancers at raves for £ 3 or £ 4 each - securing a substantial profit. Despite fears the tablets would be ground down and injected, like temazepam tablets, most swallowed them in quantities of up to 10 or 15 at a time. Illegally imported European- strength pills sold for up to double that price. He said: "Once people get the feeling for them, they will just take off. You will find they will become more and more known because doctors won't be prescribing temazepam." The Scottish Drugs Forum has learnt that drugs workers in Inverclyde had found the different strengths on sale in the area, selling for as little as 50p each. They came on sale early this year, and had begun showing up in Stirling. Dave Liddell, the agency's director, said it was too soon to predict if Rohypnol would replace temazepam after the clampdown on its availability and ban on gel-filled capsules by ministers in October. But he added: "It's something we view with concern. In some senses, there's an inevitability about something replacing temazepam. There is no surprise in relation to this, unless we get to grips with reducing the overall demand for drugs. " LANGUAGE: ENGLISH LOAD-DATE: November 14, 1995 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier pk group Page 22 LEVEL 1 - 9 OF 29 STORIES Copyright 1995 The Tribune Co. Publishes The Tampa Tribune The Tampa Tribune December 2, 1995, Saturday, FINAL EDITION SECTION: NATION/WORLD, Pg. 14 LENGTH: 500 words HEADLINE: Menace of the "date rape drug' BODY: It is hard to fathom how the drug scene in America could degenerate any further. Recently a Detroit woman was reported to have sold her 15-year-old son to a drug dealer in exchange for crack cocaine. Police say the boy spent six months as a sex slave and drug runner before being rescued. That little horror is just one more in an endless series of degradations involving crack. But a new drug is making the rounds now, with its own peculiar brand of evil. Rohypnol, known on the street as "roofies," is not just a drug of the slums, although it is used there by gang members. It is also traded in bars, dance parties and other gatherings of young people. Police in California call it "the date rape drug." Rohypnol, the brand name for flunitrazepam, is used in other countries to treat anxiety and insomnia and to sedate surgery patients. It is illegal to possess it in the United States without a foreign prescription. In a story in the Orange County Register, a spokesman for the Swiss manufacturer, the F. Hoffmann-La Roche & Co. pharmaceutical firm, said the drug must be getting into the United States through the mail or across the border from Mexican pharmacies. Local police also report the drug's appearance in our area. Pinellas County sheriff's investigators recently arrested three men in Seminole who had 38 of the tablets, along with other drugs, guns and $ 22,000 in cash. "We're starting to see it hand over fist," said Lt. Michael Platt of the Pinellas narcotics-intelligence unit. The drug is diabolically well-suited for rape, because it can be slipped into someone's drink at a bar, and within 15 to 30 minutes that person slips into a state of amnesia lasting up to eight hours. "It's like, "I think I got raped, but I don't remember, " Platt said. The victim is in danger of more than sexual assault, though. When combined with alcohol, the drug can be fatal. If being young weren't cruel and complicated enough these days, now young women have to worry about whether some creep is slipping a knock-out pill into her drink at a party. Counselors advise people to refuse a drink offered by a stranger, and never to leave one's drink unattended. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 23 The Tampa Tribune, December 2, 1995 This is a law enforcement problem, of course, but it is more than that. Here the women's rights movement and the most ardent social and religious conservatives ought to find common ground. The level of decadence and disregard for human worth required to drug and rape a young woman ought to arouse the wrath of every rational person. It would be simple if the manufacturer could just stop making the drug, but that seems unlikely. Washington ought to press researchers to consider other ways of accomplishing the same medicinal results, perhaps altering the formula or form of the drug. Shipping and dispensation should be more rigorously controlled too. Still, the problem is not so much with the manufacturer. America's drug problem is just one more symptom of the moral breakdown of much of society. TYPE: EDITORIAL; EDITORIALS LOAD-DATE: December 4, 1995 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 24 LEVEL 1 - 11 OF 29 STORIES Copyright 1995 Chicago Tribune Company Chicago Tribune November 27, 1995 Monday, EVENING UPDATE EDITION SECTION: NEWS; Pg. 2; ZONE: C; EVENING. People. LENGTH: 347 words HEADLINE: NEW DRUG FINDS WAY INTO DATE-RAPE SCENARIO BODY: A drug used in date rapes is knocking on the nation's door, according to narcotics experts in the U.S. The drug, Rohypnol, is described by law enforcement as a sedative 10 times more powerful than Valium and is manufactured by the F. Hoffmann-La Roche & Co. pharmaceutical firm, based in Basel, Switzerland. Not approved for use in the United States, it has been a legal prescription drug for several years in most of the world and is available in Europe and Latin America. On the street, users call the small, white pills "roofies" and "Roche. " The substance has also been referred to as "the date-rape drug" and "the Quaalude of the '90s," after another oft-abused sedative. Rohypnol is drawing the attention of narcotics experts across the country. It is being smuggled into the United States, usually in its original wrapping, through Colombia and Mexico, according to Bob Nichols, an assistant state prosecutor in Ft. Lauderdale, where illegal use of roofies in this country first became noticed. Nichols has been involved in five sexual-battery cases connected to roofies in the last five months. "The pattern with the rapes is that high school and college kids and gang members are slipping it into drinks at nightclubs and pickup joints, " Nichols said. Police in South Florida and Southern California report an increase in the number of women filing complaints that they felt drugged after drinking just a drink or two, and then waking up to find they had been raped. Drug counselors and law-enforcement officers are bracing for the arrival of roofies, which typically cost $1 to $5 for a single, 2-milligram pill. The pill is also taken by cocaine users who want to parachute down less harshly from a cocaine high. Reports of Rohypnol abuse have surfaced in Florida, Texas and other parts of the Southwest. Jennifer Trenshaw, health educator at the University of Southern California Health Center, had a word of advice for people, especially women: TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 25 Chicago Tribune, November 27, 1995 Don't leave your drink unattended, and don't accept a drink from a stranger. LANGUAGE: ENGLISH LOAD-DATE: January 15, 1996 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group R A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 18 LEVEL 1 - 7 OF 29 STORIES Copyright 1995 The New York Times Company The New York Times December 9, 1995, Saturday, Late Edition - Final SECTION: Section 1; Page 6; Column 1; National Desk LENGTH: 1313 words HEADLINE: In South, Drug Abusers Turn to a Smuggled Sedative BYLINE: By MIREYA NAVARRO DATELINE: MIAMI, Dec. 8 BODY: A prescription drug sold abroad is becoming the fastest-growing abused drug among young people in Florida and one that has found its way to a dozen other states, law-enforcement officials say. Manufactured by Hoffmann-La Roche, the Swiss pharmaceutical company, and sold by prescription in about 60 countries as Rohypnol, the pills are not made or approved for use in the United States. But Drug Enforcement Administration officials say the police in Florida, Texas and other Southern states are reporting an increase in smuggled shipments from Colombia, a Hoffmann-La Roche distribution site for other Latin American countries, and from Mexico, where some pharmacies sell Rohypnol over the counter. The Federal Drug Enforcement Agency has reported Rohypnol seizures in at least 13 states but says its distribution and abuse has been concentrated in Texas and Florida, where some law enforcement officials say the pills threaten to become "the Quaaludes of the '90s." Lee P. Brown, the White House drug policy director, said today that Rohypnol was an emerging drug that his office was tracking closely but that "it has by no means become a national problem." But in Florida, drug counselors say Rohypnol has found a thriving market among teen-agers who have made it the latest addition to the drug scene at nightclubs and in schools. School officials in South Florida say Rohypnol, considered a bargain at $5 or less a pill, has become almost as widely used as marijuana and LSD among students. Officials in Dade County, where the sedative first surfaced in 1989, have become concerned enough that they have begun routine testing for Rohypnol in cases where the driver appears drunk but registers low alcohol levels. The medical examiner's office will soon begin to test for Rohypnol in cases in which women say they might have been raped but do not remember. In Texas, where Hoffman-La Roche is financing an epidemiological study to examine why Rohypnol is being abused, researchers say it is mostly taken by users of other drugs who find it more potent than other sedatives. Cocaine TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 19 The New York Times, December 9, 1995 addicts say Rohypnol helps them come down more smoothly from their high; heroin users say it offsets their withdrawal symptoms. Known among American users as "roofies,' from the mispronunciation of the brand name, and sometimes as "roach" or "rope," Rohypnol is a benzodiazepine, a class of sedatives that includes Valium. Marketed in 1- or 2-milligram dosages, it induces muscle relaxation, short-term amnesia and sleep. Its effect, felt within 15 to 20 minutes and lasting eight hours or more, is similar to that of alcohol in that it helps loosen inhibitions before sedation takes hold. Frequent users can develop tolerance and get addicted, requiring treatment. In Miami, officials at the Up Front Drug Information Center said its hot line had received calls from teen-age girls who said they had grown dependent on Rohypnol and wanted help. When combined with alcohol or other drugs, drug experts say, it can cause respiratory depression and death. Kurt Cobain, the grunge rock singer, collapsed and slipped into a brief coma a month before his suicide last year after ingesting Rohypnol with champagne in a hotel room in Rome. While in Europe and Latin America Rohypnol is mainly known as a sleeping aid and pre-surgery anesthetic (although it is also abused), many here learned of its existence in startling ways. Drug information hotlines started to hear from parents wondering about the pills they had just found in their child's pocket. Teachers called paramedics because a student had passed out. At Miami Palmetto Senior High School, the school newspaper reported, a junior was taken to the hospital when a friend noticed she missed her mouth while eating nachos. Now, 20 percent of the patients at the adolescent drug abuse program at Jackson Memorial Hospital say they have taken Rohypnol, doctors there said. In Dade County schools, 21 cases of Rohypnol possession or use have been reported to police since they began tracking the drug five months ago. In Broward County, north of here, prosecutors say they handled two rape cases recently and are investigating two others where men gave the drug to women and then sexually assaulted them. In one case, the pill was slipped into the woman's drink while she visited the defendant. The man then bragged he had done the same to a dozen other women. "When they wake up, they're completely naked and the defendant is sitting next to them in his underwear,' said Assistant State Attorney Bob Nichols, adding that both defendants pleaded guilty and went to prison. "These girls are all in therapy because they can only imagine what happened. Since Dade County began testing drunk drivers for Rohypnol, 35 drivers have tested positive for the drug, making roofies the most popular among caught drivers after marijuana and cocaine, said Dr. Lee Hearn, director of the toxicology laboratory at the county's medical examiner's office. "Police are reporting that they stop them for driving really badly and when they open the door, they fall out,' he said. Its low price and harmless look, bubble-wrapped like so much medicine, may TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 20 The New York Times, December 9, 1995 explain some of the drug's popularity, drug counselors and police said. At Miami Palmetto High, Rene C., a 16-year-old junior, said he liked it because "it gets you drunk. " Maria B., an 18-year-old senior, said she only took roofies on special occasions to feel relaxed. "You don't hear anything bad about it, like heroin or crack, where people die or anything," she said. They were able to obtain Rohypnol from both classmates and friends, the students said. In Florida, Rohypnol is mainly smuggled through the mail and delivery packages or in luggage, DEA officials say. In Texas, the drug comes in through border crossings, often legally. A recent survey by the University of Texas College of Pharmacy in Austin found that 43 percent of those declaring prescription drugs in customs forms at the border brought Rohypnol. Only Valium was declared more frequently. The Food and Drug Administration generally allows people to bring drugs sold abroad but not approved here but only for their personal use, defined as a three-month supply. But once in, the drug is considered illegal by law enforcement officials. They said Rohypnol was a controlled substance and its possession punishable by both fines and prison. D.E.A. officials have reported seizures of more than 50,000 pills at a time in both Texas and Louisiana, and they say they are concerned about the involvement of cocaine and marijuana traffickers in Rohypnol's distribution. So are drug counselors, who say they worry that it may be used by dealers to hook children on other drugs. "We feel South Florida is a test market for this drug," said James Hall, of Up Front Drug Center here. Alfred J. Wasilewsky, a spokesman for Hoffmann-La Roche's affiliate in the United States, said the company was working on altering Rohypnol's dosage to try to make it less attractive. He said the presence of similar products in the market dissuaded the company from seeking approval to sell the drug in the United States. In South Florida, school officials have added roofies to their group counseling and classroom discussions. In Texas, the state's Commission on Alcohol and Drug Abuse is about to send out 10,000 fliers on the drug to school nurses and has added a question about Rohypnol to its survey of 100,000 4th to 12th-graders about drug use, which is given every other year. But the Miami Palmetto Senior High School principal, Leonard Glazer, noted that alcohol, not roofies, remained the biggest problem in schools. "I think we tend to overlook that in the high school scene, alcohol is the introducer,' he said. "Once your inhibitions have been lowered by alcohol, you're more likely to experiment." GRAPHIC: Photo: The fastest-growing abused drug in Florida is the Rohypnol pill, made by Hoffmann-La Roche. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 21 The New York Times, December 9, 1995 Map: "A CLOSER LOOK: Abusing a Sedative" Siezures by law-enforcement agencies of the prescription sleeping pill Rohypnol, which is not approved for sale in the United States, have risen sharply in certain states. Map of continental U.S. shows states where the greatest quantities of Rohypnol have been siezed, along with other states where the drug has been siezed. (Source: Drug Enforcement Administration) LANGUAGE: ENGLISH LOAD-DATE: December 9, 1995 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 16 LEVEL 1 - 6 OF 29 STORIES Copyright 1995 Denver Publishing Company Rocky Mountain News December 10, 1995, Sunday SECTION: NEWS/NATIONAL/INTERNATIONAL; Ed. B; Pg. 2A LENGTH: 400 words HEADLINE: New drug threatens U.S. youth Florida, Texas report rising use of Rohypnol, prescription sedative sold abroad, illegal in U.S. BYLINE: Mireya Navarro; The New York Times DATELINE: MIAMI BODY: A prescription drug sold abroad is becoming the fastest- growing abused drug among young people in Florida and one that has found its way to a dozen other states, law-enforcement officials say. Manufactured by Hoffmann-La Roche, the Swiss pharmaceutical company, and sold by prescription in about 60 countries as Rohypnol, the pills are not made or approved for use in the United States. But federal Drug Enforcement Agency officials say the police in Florida, Texas and other Southern states are reporting an increase in smuggled shipments from Colombia, a Hoffmann-La Roche distribution site for other Latin American countries, and from Mexico, where some pharmacies sell Rohypnol over the counter. The DEA has reported Rohypnol seizures in at least 13 states but says its distribution and abuse has been concentrated in Texas and Florida, where some law enforcement officials say the pills threaten to become ''the Quaaludes of the '90s. Lee P. Brown, the White House drug-policy director, said Friday that Rohypnol is an emerging drug that his office is tracking closely but that ''it has, by no means, become a national problem. But in Florida, drug counselors say Rohypnol has found a thriving market among teen-agers who have made it the latest addition to the drug scene at nightclubs and in schools. School officials say Rohypnol has become almost as widely used as marijuana and LSD. In Texas, where Hoffman-La Roche is financing an epidemiological study to examine why Rohypnol is being abused, researchers say it is taken mostly by users of other drugs who find it more potent than other sedatives. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier pk group A member of the Reed Elsevier plc group Page 17 Rocky Mountain News, December 10, 1995 Known among American users as ''roofies, from the mispronunciation of the brand name, and sometimes as ''roach'' or ''rope, Rohypnol is a benzodiazepine, a class of sedatives that includes Valium. The drug induces muscle relaxation, short-term amnesia and sleep. LANGUAGE: English LOAD-DATE: December 13, 1995 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier pic group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 14 LEVEL 1 - 5 OF 29 STORIES Copyright 1995 Denver Publishing Company Rocky Mountain News December 10, 1995, Sunday SECTION: NEWS/NATIONAL/INTERNATIONAL Ed. F; Pg. 95A LENGTH: 374 words HEADLINE: New drug takes hold among teens Florida, Texas report surging use of Rohypnol, sold legally in 60 countries but not U.S. BYLINE: Mireya Navarro; The New York Times DATELINE: MIAMI BODY: A prescription drug sold abroad is becoming the fastest- growing abused drug among young people in Florida and has found its way to a dozen other states, law-enforcement officials say. Manufactured by Hoffmann-La Roche, the Swiss pharmaceutical company, and sold by prescription in about 60 countries as Rohypnol, the pills are not made or approved for use in the United States. Federal Drug Enforcement Agency officials say police in Florida, Texas and other southern states are reporting an increase in smuggled shipments from Colombia, a Hoffmann-La Roche distribution site for other Latin American countries, and from Mexico, where some pharmacies sell Rohypnol over the counter. The DEA has reported Rohypnol seizures in at least 13 states but says its distribution and abuse has been concentrated in Texas and Florida, where some law enforcement officials say the pills threaten to become ''the Quaaludes of the '90s. Lee P. Brown, the White House drug-policy director, said Friday that Rohypnol is an emerging drug that his office is tracking closely but that ''it has, by no means, become a national problem. In Florida, drug counselors say Rohypnol has found a thriving market among teen-agers who have made it the latest addition to the drug scene at nightclubs and in schools. School officials say Rohypnol has become almost as widely used as marijuana and LSD. In Texas, where Hoffman-La Roche is financing an epidemiological study to examine why Rohypnol is being abused, researchers say it is taken mostly by people who find it more potent than other sedatives. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 15 Rocky Mountain News, December 10, 1995 Rohypnol is a benzodiazepine, a class of sedatives that includes Valium. The drug induces muscle relaxation, short-term amnesia and sleep. LANGUAGE: English LOAD-DATE: December 12, 1995 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS R A member of the Reed Elsevier plc group A member of the Reed Elsevier pk group A member of the Reed Elsevier pk group Page 9 LEVEL 1 - 4 OF 29 STORIES Copyright 1995 The Dallas Morning News THE DALLAS MORNING NEWS December 17, 1995, Sunday, BULLDOG EDITION SECTION: NEWS; Pg. 40A LENGTH: 1655 words HEADLINE: Police suspect illegal sedative used in date rapes BYLINE: Julio Laboy, Orange County Register DATELINE: SANTA ANA, Calif. BODY: SANTA ANA, Calif. - It started out as a casual get-together for a 25-year-old student but ended in rape, humiliation and the harrowing revelation that a drug used in date rapes is knocking on the nation's door. The drug, Rohypnol, is described by law enforcement as a sedative 10 times more powerful than Valium and is manufactured by the F. Hoffmann-La Roche & Co. pharmaceutical firm, based in Basel, Switzerland. Not approved for use in the United States, it has been a legal prescription drug for several years in most of the world and is available in Europe and Latin America. The sale and introduction of the drug into interstate commerce in the United States is illegal; virtually the only people who can possess it legally in this country are those who have prescriptions written in other countries. On the street, users call the small, white pills "roofies" and "Roche." The substance has also been referred to as "the date rape drug" and "the Quaalude of the '90s," after another oft-abused sedative. Rohypnol is drawing the attention of narcotics experts across the country. It is being smuggled into the United States, usually in its original wrapping, through Colombia and Mexico, according to Bob Nichols, an assistant state prosecutor in Fort Lauderdale, Fla., where illegal use of roofies in this country first was noticed. Mr. Nichols has been involved in five sexual-battery cases connected to roofies in the last five months. "I don't know why it's suddenly on the scene. It's been around awhile,' " Mr. Nichols said. "The pattern with the rapes is that high school and college kids and gang members are slipping it into drinks at nightclubs and pick-up joints." That is what one Orange County, Calif., woman, an English major at the University of California, San Diego, thinks happened to her Sept. 29. The student attended a concert that night with a male friend. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plo group Page 10 THE DALLAS MORNING NEWS, December 17, 1995 The two were not romantically involved, she said. She had three glasses of wine that night. At least one glass of wine was consumed in the parking lot of the San Diego theater where the concert was taking place. That's when the student started feeling strange. She doesn't remember the concert. She doesn't remember how she got home. She doesn't remember getting into bed. The last thing she does recall is waking up the next morning naked and in a pool of vomit. "I was so sick when I woke up," she said. "I could hardly hold my head up. I couldn't remember anything. I noticed there was vomit on the bed and stuck on my hair. I was lying in it. I could have choked on it and died. He was naked and I was naked. He said we made love. " The woman was crushed. Their relationship had never been an intimate one, she said. The Orange County Register , which generally doesn't publish the names of sexual-abuse victims, is withholding her name from publication. The woman, who works as a part-time language teacher and as a waitress, thinks that her companion slipped a roofie into her wine that night and that it erased her memory, an effect described by pharmacologists and in medical reports. Struggling to overcome the nightmare, the woman is seeing a therapist and is taking a vacation out of the country to escape the everyday reminders of that ill-fated night. She agreed to share her story because, she said, "I didn't do anything wrong. " She wants to turn a negative experience into a positive one. She wants to warn other young women about roofies. "My friends had no clue about this drug, " she said. "This stuff is scary. You can't be cautious enough. " She called a rape hotline after spending two lonely days knee-deep in guilt and self-doubt. She then went to a therapist at Kaiser Permanente in San Diego. "Some people were saying I got drunk. But I didn't. I just had wine, the student said. "I was telling the therapist that I couldn't believe it. I was crying. I was confused. As I started telling her my story she said, Hold on. I know what this is. II The student learned from the therapist that her situation resembled a drugging and that an epidemic of similar cases had arisen in the past six months. "She said they all were feeling sluggish and drunk on dates that ended in rape, If the student said. That's when the student first heard about roofies. "We have seen many date-rape cases,' 11 Kaiser Permanente spokesman Jim McBride said. "Many of those patients report being drugged. Our therapists believe TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier pk group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 11 THE DALLAS MORNING NEWS, December 17, 1995 these stories are credible. It's real. It's happening." The woman then notified the San Diego Police Department. Investigators are looking into the matter. Police Sgt. Joanne Archambault of the sex-crimes unit said she cannot comment on rape cases because of privacy reasons, but she confirmed that the student's report had been taken. "Recently, lots of girls have been coming in saying they were drugged or passed out after having one or two drinks,' Sgt. Archambault said. "We even talked to the Poison Control Center about it. " Orange County drug counselors and law-enforcement officers are bracing for the arrival of roofies, which typically cost $ 1 to $ 5 for a single, 2-milligram pill. "I would assume that because of the movement of things in the San Diego-Los Angeles-Orange County corridor, that yes, it may be here," said Bill Edelman, division manager in charge of alcohol and drug programs at the Orange County Health Care Agency. Reports of Rohypnol abuse have surfaced in Florida, Texas and other parts of the Southwest, he said. Jennifer Trenshaw, health educator at the University of Southern California Health Center, sai she advised people, especially women, not to leave their drinks unattended and not to to accept drinks from strangers. The UCSD student who says she was raped remembers going to the bathroom twice during the concert. She left her drink with her date. The student described all the classic circumstances and side effects of a roofie mixed with alcohol, Mr. Edelman said. "It's a sedative. It's a drug that can be enhanced when it is combined with alcohol or opiates,' Mr. Edelman said. Rohypnol, the brand name for Flunitrazepam, is used in other countries to treat anxiety and insomnia and to sedate surgery patients, according to pharmacologists and drug-information centers. Patients on the drug appear drunk. When it's combined with alcohol, the effects can be deadly. "These guys using this to get girls are like those people who like to do things with dead bodies, " Mr. Edelman said. "It's sick. Maybe we need to think about a campaign about how this drug is used in bars. " Al Wasilewski, a spokesman for the pharmaceutical company's U.S. division, said the drug is being illegally mailed into the United States. He also said that some Mexican pharmacies near the U.S. border are illegally selling the drug over the counter. He said Hoffmann-La Roche has never sought approval to market the drug in the United States. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier pk group A member of the Reed Elsevier plc group Page 12 THE DALLAS MORNING NEWS, December 17, 1995 "It's a legitimate product sold for legitimate use in those countries where it's registered, " Mr. Wasilewski said. He disagreed with law-enforcement officials who have described the drug as being 10 times more powerful than Valium but acknowledged that taken in equal doses, Rohypnol will act more quickly and more powerfully than Valium. "They are two different drugs designed to do two different things, If Mr. Wasilewski added. "It was about a year ago when we began to see just more than sporadic abuse of Rohypnol." Hoffmann-La Roche has initiated studies to learn more about how the drug is being abused, where it's coming into the United States, and where in the country it is most likely to be found. The company is trying to track its movement throughout the country and recently helped set up a task force with members drawn from federal and local law-enforcement agencies, academics and drug-counseling centers, Mr. Wasilewski said. The company has also disseminated alerts to the health-care industry and police departments. Hoffmann-La Roche has divisions in Mexico City and Bogota, Colombia, where Rohypnol is manufactured for the Latin American market. "We're doing everything that is possible for Roche to get this product off the streets, " Mr. Wasilewski said. "We're confident that the diversion of Rohypnol is not occurring internally from our sites in Mexico and Colombia." Dr. Jim Adams, associate professor of molecular pharmacology and toxicology at USC's School of Pharmacy, said Flunitrazepam can make someone lose control of motor and neurological functions. Respiration is also affected. When it's mixed with alcohol, he said, a coma can easily follow. Vomiting also can occur, and if a victim is unconscious, he or she runs the risk of drowning in the discharge. The drug reacts with brain cells to quickly diminish nervous system operations, said Dr. Edward Newton, a consultant to the Los Angeles Regional Poison Control Center. The area the center serves includes Orange County. "It depresses neurological activity in the brain," Dr. Newton said. "People do die if they take too much." It is difficult to determine a lethal dose of Rohypnol because reactions to sedatives differ among individuals, and when taken alone it is not difficult to manage, according to the Up Front Drug Information and Education Center in Miami. An overdose is more likely when Rohypnol is mixed with alcohol or other drugs. The speed with which the overdose will take place depends on how much alcohol a person has consumed. A roofie will sedate its user quickly. Sedation occurs 15 to 30 minutes after ingestion and lasts about eight hours, USC's Ms. Trenshaw said. If an overdose occurs, the need for medical care is urgent. An added problem with Rohypnol is that it causes amnesia for most of the sedation period, especially during a patient's first consumption. That makes prosecution of abuse cases difficult, Ms. Trenshaw said. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 13 THE DALLAS MORNING NEWS, December 17, 1995 LANGUAGE: ENGLISH LOAD-DATE: December 18, 1995 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS R member of the Reed Elsevier plc group R A member of the Reed Elsevier pk group R A member of the Reed Elsevier plc group Page 2 LEVEL 1 - 1 OF 29 STORIES Copyright 1996 Star Tribune Star Tribune January 16, 1996, Metro Edition SECTION: Variety; Pg. 1E LENGTH: 654 words HEADLINE: FYI; 'Date-rape' drug BYLINE: Dave Matheny; Staff Writer BODY: Rohypnol, a potent sedative-hypnotic drug, has made its way to Minnesota. Rohypnol is a sleeping pill used in Mexico but not approved for use in the United States. It has been abused primarily by young people who combine the drug with alcohol. Because of its amnesialike effects it also is being used as a date rape drug, according to a drug alert issued by the Minnesota Department of Human Services. In southern Minnesota, abuse of the drug has been suspected in several cases in which some is placed in alcoholic beverages of young women who are subsequently exploited sexually. Victims have no recall of the events following sedation. Rohypnol has a bitter taste when added to a beverage and is about 10 times more potent than Valium. For more information on this drug, call the Minnesota Prevention Resource Center at 427-5310 (metro) or (800) 247-1303. - Hazelden Foundation Saddam happens Five years ago today, the Gulf War suddenly became real, as Allied jets swept into Iraq. We're indebted to "War Slang" by Paul Dickson (Pocket Books hardcover; $ 25) for the following information. There is something appealing about slang that grows up around particular pursuits or disciplines, especially hazardous ones: It reflects how we adapt to hardship and even to the possibility of being killed. Dickson includes sections on specialized slang from the Civil War up through the present. Here are a few from the Gulf War: - Diver: CNN reporter Charles Jaco, known for diving off camera during Scud alerts. - Homer: A member of the Iraqi army (based on bumbling Homer Simpson). - Little Hollywood: Area near the swimming pool of the Dharhran hotel, from which TV correspondents frequently delivered their live reports, often wearing TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS R A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 3 Star Tribune, January 16, 1996 helmets, flak jackets and goggles, while the camera crews wore T-shirts. Mysterious blue domes seen in the background actually were pool cabanas and storage sheds. - Poor man's defense: The Iraqi tactic of filling the sky with randomly aimed gunfire, as was seen over Baghdad almost nightly. - Saddam Happens: Bumper sticker seen on the back of a tank. - Speed bumps: At first, the handful of U.S. troops on the Saudi Arabian side of the border, facing the massed Iraqi forces on the other side; if the Iraqis had attacked, the Americans saw themselves as little more than speed bumps. Later the term was applied to Iraqi soldiers. (By the time the war ended, Iraqi troops had been killed by Allied forces at a ratio of about 1,000 to one. In fact, the Pentagon later said that more Americans would have died if the troops had remained stateside during the same period, largely from road accidents.) - W.T.O.: The Washington Theater of Operations - an ironic reference. In a subsection titled "Murphy's Laws for Grunts,' Dickson includes a list of 29 laws. A sampling: - When in doubt, empty your magazine. - If the enemy is in range, so are you. - Tracers work both ways. - The easy way is always mined. - Dave Matheny This week Thinking about the warm One way to take the edge off of winter is to go to a big indoor place where they pretend it's some other season - summer, for example. Actually, the annual Minnesota Sportsmen's Boat, Camping and Vacation Show isn't just for warm-weather activities, but that's what comes to mind for most folks: Boats, RVs, hunting and fishing stuff is what it's about. As usual there are displays and demonstrations, including a live trout pond and stage shows. - What: 1996 Minnesota Sportsmen's Boat, Camping and Vacation Show - When: Today, 5 to 10:30 p.m.; noon to 10:30 p.m. tomorrow through Friday; 10 a.m. to 10:30 p.m. Saturday; 10 a.m. to 6:30 p.m. Sunday. - Where: St. Paul Civic Center, St. Paul. TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group A member of the Reed Elsevier plc group Page 4 Star Tribune, January 16, 1996 - Admission: $ 6 adults, $ 2 children under 12; preschoolers free. GRAPHIC: Illustration LANGUAGE: ENGLISH LOAD-DATE: January 17, 1996 TM TM TM LEXIS-NEXIS LEXIS-NEXIS LEXIS-NEXIS A member of the Reed Elsevier plc group A member of the Reed Elsevier pic group A member of the Reed Elsevier plc group CFR Index code of and Finding Aids PRNS LIBRARY Reem Washington, DC 20800 federal regulations Revised as of January 1, 1995 EXECUTIVE OFFICE OF THE PRESIDENT MAY JU 1995 LAW NATION AND RECORDS 1985 R Index Authorities R 21 U.S.C.-Continued CFR 21 U.S.C.-Continued CFR 21 U.S.C.-Continued CFR 1, 53, 56, 72. 73, 75-79, 85, 91, 160-162 334 21 Part 800 206, 207, 211, 225, 226, 299, 329, 429, 98 120 7 Part 1 336 21 Parts 58, 432, 433, 607, 640, 803, 804, 895, 1040. 0, 9 Parts 49, 70, 82. 93, 99 109, 130, 250, 509 1050 01 122-123 9 Parts 49, 70 337 21 Part 100 353 21 Parts 310, 312, 329, 500 60 122 7 Part 1 341-343 21 Parts 70, 355-360a 21 Part 514 60 9 Part 93, 99 73, 74, 156 355-358 21 Part 201 34 123-126 9 Parts 56, 341 21 Parts 71, 355-357 21 Part 3. 11 72, 73, 75, 76, 78, 79, 82, 85 103-105, 130, 131, 133, 135-137, 139, 50, 56, 58, 71, 170, 171, 202, 207, 211. 0 125-127 9 Parts 49, 70 145, 146, 150, 152, 155, 156, 158, 160, 312, 314, 320, 361, 430, 505, 510, 570. 0 125 9 Parts 50, 51. 160-162 161, 163-166, 168-176, 178, 300, 556, 571, 700, 800, 812, 813, 1003 7 127 7 Part 1 564, 571, 573, 584 355-356 21 Part 200 10 134-134h 9 Part 75 342-343 21 Parts 100, 355 21 Parts 1. 2. 0 134a 9 Parts 82, 93 179, 501, 505, 514, 801 12, 60, 73, 74. 206, 250, 290, 291, 299. 36 134a-134h 9 Parts 54, 56 342 21 Parts 58, 300, 310, 330-333, 336, 338, 340, 341. 15 134a-134d 9 Parts 92, 98 7 108-110, 113, 114, 122, 129, 170, 172, 344, 347-349, 357, 433, 500, 501, 600, 134a-134c 9 Part 94 8 134b-134c 181, 182, 184, 186, 189, 250, 500, 507- 601, 606, 607, 610. 620, 630, 640, 801, 9 Parts 49, 70, 93, 99 7 134b 9 Parts 50, 51, 509, 570, 589 809 343 8 53, 71-73, 76-80, 82, 85, 91, 99, 160, 21 Parts 1, 356-357 21 Parts 369, 429 8 161, 162 101-105, 107, 130, 131, 133, 135, 136, 356 21 Part 310 134d 9 Part 93 139, 145. 160, 161, 163, 164, 166, 168, 357-358 21 Part 200 2 134e-134f 169. 502, 564 357 21 Parts 2, 5 7 Part 1 2 9 Parts 49, 70, 93, 99 344 21 Parts 108, 508 60, 206, 300, 320, 430-433, 436, 440- 2 134f 9 Parts 71-73, 345 21 Part 561 444, 446, 448-450, 452, 453, 455, 460, 7 76-80, 82, 85, 91, 92. 94, 98, 99, 160- 346-346a 21 Parts 50, 500, 501, 544, 801, 809 358 21 Part 299 2 162 56, 58, 71, 109, 170, 171, 193, 320, 361, 360-360 note 135-135a 430, 431, 514, 570, 571, 812, 813, 1003, 21 Parts 606, 610 9 Parts 93, 99 360 21 Parts 3. 4 135 9 Part 92 1010 135a 7 Parts 1, 319 40 Parts 2, 180 20, 50, 56, 58, 71, 170. 171, 180, 201, 0 136-136a 7 Parts 320, 346 21 Parts 175, 207, 225, 310, 320, 330, 332, 333, 336, 338, 340, 341, 344, 347, 348, 349, 357, 330, 352, 354 176, 178, 250, 509, 561 5 9 Parts 91, 92, 95, 96, 130 21 Part 2 361, 430, 510, 511, 520, 571, 600, 607, 346a 7 640, 803, 804, 809, 812-814, 821, 862, 9 136a 7 Part 319 40 Parts 9, 23, 864, 866, 868, 870, 872, 874, 876. 878, 9 Part 156 160, 163, 178, 179, 185 8 880, 882, 884, 886, 888, 890, 892, 1010, 141-149 21 Parts 5, 10, 12-16 346c 21 Part 561 1 1030, 1040, 1050 151-159 9 Parts 101-109, 116-118 347 21 Parts 1, 166 2 360b-360f 21 Parts 58, 21 Part 112 40 Part 180 8 71, 170, 171, 180, 314, 430, 431, 511, 2 151-158 9 Parts 113, 114, 122, 123 348 21 Parts 50, 570, 571. 812, 1003, 1010 32 Part 627 56, 58, 60, 70, 71. 73, 100, 101, 103, 360b-360c 21 Part 12 154 7 Part 1 105, 109, 129. 131, 133, 135-137. 139, 360b 21 Parts 1, 2. 159 9 Part 113 145. 146, 150, 156, 161, 163, 164, 166, 70, 201, 207, 225, 226, 250, 299, 300, 262 21 Part 56 168-173, 175-182, 184, 186, 189, 320, 453, 505, 514, 520, 522, 524, 526, 529, 271 21 Parts 500, 505 361, 430, 500, 501, 509, 570, 571, 573, 556, 558, 801, 809 301 note 21 Part 101 579, 582, 584. 589, 700, 801, 813, 1003 360c-360j 21 Part 814 321 et seq 21 Parts 10, 13, 514 40 Parts 9, 23, 360c-360f 21 Parts 3, 7 321-394 21 Part 5 160, 177-180, 185, 186 50, 56, 310, 320, 361, 510, 813 321-393 21 Parts 7, 348a 21 Part 156 360c-360e 21 Parts 20, 860 10, 12-16, 20, 25 350 21 Part 105 360c-360d 21 Parts 809, 861 321-371 21 Part 14 350a 21 Parts 7. 106, 107 360c 21 Part 807, 321 21 Parts 1-3, 351-353 21 Parts 3, 862, 864, 866, 868, 870, 872, 874, 876, 50, 56, 70, 71, 73, 74, 100-107, 109, 130, 56, 71, 170. 171, 180, 200, 201, 205, 312, 878, 880, 882, 884, 886, 888, 890, 892 131, 133, 135, 137, 145, 156, 160, 161, 314, 320, 330-333, 336, 338, 340, 341, 360e-360j 21 Parts 1010, 163, 164, 166, 168-179, 181, 182, 184, 344, 347, 348, 349, 357, 430, 431, 506, 1020, 1030, 1040, 1050 186, 189, 200-202, 206, 207, 211, 250, 510, 511, 514. 570, 571, 600, 616, 620, 360e 21 Parts 60, 200, 310, 312, 314, 330-333, 336, 338, 340, 630, 640, 812-814, 1003, 1010 800, 820, 821, 862, 864, 866, 868, 870, 341, 344, 347-349, 357, 361, 369, 430- 351-352 21 Parts 2, 872, 874, 876, 878, 880, 882, 884, 886, 432, 500-502, 505, 510, 511, 570, 573, 20, 299, 300, 500, 501, 600, 606, 700, 888, 890, 892 579, 582, 584, 589, 600, 606, 607, 610, 800, 801, 807, 809, 820, 821, 861 360f 21 Part 895 640, 700, 710, 730, 740, 800, 801, 1020 351 21 Parts 70, 73, 360h-360j 21 Parts 3, 331 21 Parts 2, 210, 211, 225, 226, 310, 351, 505, 607, 50, 56, 58, 71, 171, 180, 320, 361, 430, 20, 100, 201, 206, 299, 300, 500, 501, 862, 864, 866, 868, 870, 872, 874, 876, 431, 809, 812, 813, 820, 1003, 1010 505, 510, 730, 807, 809, 812, 813, 821 878, 880, 882, 884, 886, 888, 890, 892, 360h-3601 21 Parts 170, 571, 821, 895 40 Part 177 1010, 1020, 1030, 1040, 1050 3601-360j 21 Parts 20, 801, 860 331j 40 Part 9 352-353 21 Parts 50, 3601 21 Parts 800, 332-334 21 Part 110 58, 202, 250, 290, 310, 361, 369 803, 804, 862, 874, 900 333 21 Part 7 352 21 Parts 1, 73, 3601 21 Parts 60, 606, 786 787 UNITED STATES CODE ANNOTATED Title 21 Food and Drugs §§ 1 to 800 1995 Supplementary Pamphlet Covering Years 1973 to 1994 Replacing 1994 pocket part in back of 1972 bound volume Includes the Laws of the 103rd CONGRESS, SECOND SESSION (1994) For close of Notes of Decisions See page III For Later Laws and Cases Consult USCA Interim Pamplet Service 1993 NEW Please detach the perforated card-from inside the front cover and place it in the pocket part slot of the corresponding main volume as a reminder to refer to this supplementary pamphlet. WEST PUBLISHING CO. ST. PAUL, MINN. 21 § 353 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 Note 7 tiality for harmful effects through excessive use Morse V. Riverside Hospital, 1974, 339 N.E.2d to the merely average man and even to those the Secretary as a part of the application (A) full reports of investigations which have 846, 44 Ohio App.2d 422. below the average. National Nutritional Foods been made to show whether or not such drug is safe for use and whether such drug is Ass'n V. Weinberger, D.C.N.Y.1978, 866 F.Supp. 18. - Weight and sufficiency effective in use; (B) a full list of the articles used as components of such drug; (C) a full 1841, affirmed 491 F.2d 845. Public promotion of high dosage quantities of statement of the composition of such drug; (D) a full description of the methods used in, Commissioner is not required to set over-the- vitamins A and D for the cure, mitigation, treat- and the facilities and controls used for, the manufacture, processing, and packing of such counter limit beyond which drug may be ob- ment, and prevention of a variety of ailments, drug; (E) such samples of such drug and of the articles used as components thereof as tained only by prescription, at maximum which when coupled with the fact that there exists the Secretary may require; and (F) specimens of the labeling proposed to be used for consumer might withstand; substantial margin little, if any, evidence of known nutritional re- such drug. The applicant shall file with the application the patent number and the of safety may be used. National Nutritional quirements above the levels of 10,000 IU per Foods Ass'n V. Weinberger, D.C.N.Y.1973, 366 expiration date of any patent which claims the drug for which the applicant submitted dosage unit of vitamin A and 400 IU per dosage F.Supp. 1341, affirmed 491 F.2d 845. the application or which claims a method of using such drug and with respect to which a unit of vitamin D was sufficient to demonstrate 11. Elements of offense that Food and Drug Administration require- claim of patent infringement could reasonably be asserted if a person not licensed by the ments that preparations of vitamins A and D owner engaged in the manufacture, use, or sale of the drug. If an application is filed Where federal law prohibits dispensing of a above those levels be restricted to prescription under this subsection for a drug and a patent which claims such drug or a method of drug without a prescription, propriety of secur- sale and be labeled accordingly was not arbi- using such drug is issued after the filing date but before approval of the application, the ing and adjusting that drug without a prescrip- trary or capricious. National Nutritional Foods tion does not depend upon user's knowledge of applicant shall amend the application to include the information required by the the particular dangers involved. Lindsay V. Or- Ass'n V. Mathews, D.C.N.Y.1976, 418 F.Supp. preceding sentence. Upon approval of the application, the Secretary shall publish 394. the Pharmaceutical Corp., C.A.N.Y.1980, 637 information submitted under the two preceding sentences. F.2d 87. Although evidence sufficient to support find- ing that high potency preparations of certain (2) An application submitted under paragraph (1) for a drug for which the investiga- 12. Jurisdiction vitamins had no demonstrated usage as a food, tions described in clause (A) of such paragraph and relied upon by the applicant for Reason Food and Drug Administration has at least for all but an extremely small percent- approval of the application were not conducted by or for the applicant and for which the primary jurisdiction to determine whether drug age of the population, above levels established in applicant has not obtained a right of reference or use from the person by or for whom sought to be marketed constitutes "new drug" Food and Drug Administration regulations re- the investigations were conducted shall also include- subject to this chapter is expertise of Federal quiring that high potency preparations be avail- (A) a certification, in the opinion of the applicant and to the best of his Drug Administration in resolving technical and able for sale only by prescription and be labeled scientific questions. Biotics Research Corp. V. accordingly, might not, standing alone, be suffi- knowledge, with respect to each patent which claims the drug for which such Heckler, C.A.Nev.1988, 710 F.2d 1375. cient to sustain the regulations, it was a relevant investigations were conducted or which claims a use for such drug for which the 18. Persons liable and important data in favor of the regulations. applicant is seeking approval under this subsection and for which information is National Nutritional Foods Ass'n V. Mathews, required to be filed under paragraph (1) or subsection (c) of this section- Under "bulk supplier doctrine," bulk supplier D.C.N.Y.1976, 418 F.Supp. 894. of polytetrafluoroethylene (PTFE) to manufac- (i) that such patent information has not been filed, turer of jaw joint implant, which was regulated 19a. Witnesses (ii) that such patent has expired, by the Food and Drug Administration (FDA), Commissioner of food and drugs would not be (iii) of the date on which such patent will expire, or did not have any duty to warn of possible dan- called at "Overton-type" hearing, which was be- gers of PTFE in implant, and thus, patients (iv) that such patent is invalid or will not be infringed by the manufacture ing held to determine whether the Food and could not recover from supplier for injuries al- Drug Administration acted rationally in requir- use, or sale of the new drug for which the application is submitted; and legedly received as result of implant, on breach ing that preparations of vitamins A and D in (B) if with respect to the drug for which investigations described in paragraph of duty to warn theory; FDA approved PTFE excess of specified dosages be restricted to pre- (1)(A) were conducted information was filed under paragraph (1) or subsection (c) of as appropriate medical device for use in a medi- scription sale and be labeled accordingly, for cal implant, and before filling the order, supplier this section for a method of use patent which does not claim a use for which the informed manufacturer of its lack of knowledge cross-examination by those opposing the actions applicant is seeking approval under this subsection, a statement that the method of taken by the Food and Drug Administration. of whether use of device in implants was appro- use patent does not claim such a use. priatc. Veil V. Vitek, Inc., D.N.D.1992, 803 National Nutritional Foods Ass'n V. Mathews, F.Supp. 229. D.C.N.Y.1976, 418 F.Supp. 394. (3)(A) An applicant who makes a certification described in paragraph (2)(A)(iv) shall R.C. Ohio §§ 8715.01(A) (5) (a), (A) (6) (a), (B) 21. State regulation or control include in the application a statement that the applicant will give the notice required by subparagraph (B) to- (2) do not apply to the administration of a drug Lethal injection statute was not preempted by or device by a licensed member of the medical Federal Drug Abuse Prevention and Control Act (i) each owner of the patent which is the subject of the certification or the profession. Morse V. Riverside Hospital, 1974, (DAPCA) or Federal Food, Drug and Cosmetic representative of such owner designated to receive such notice, and 839 N.E.2d 846, 44 Ohio App.2d 422. Act (FDCA); Statute's single goal was merely to (ii) the holder of the approved application under subsection (b) of this section for Complaint brought by patient who contracted effect execution of lawfully condemned inmates, the drug which is claimed by the patent or a use of which is claimed by the patent hepatitis during a blood transfusion did not state in contrast to the federal Acts' concerns over or the representative of such holder designated to receive such notice. a valid claim for relief against hospital and blood deleterious effects of unregulated usage of con- bank based upon negligence by reason of a trolled substances by individual citizens, and (B) The notice referred to in subparagraph (A) shall state that an application has violation of R.C. Ohio § 3715.01(A) (5) (a), (A) (6) statute could not violate federal law, inasmuch been submitted under this subsection for the drug with respect to which the certification (a), (B) (2), inasmuch as provisions thereof did as federal government utilized lethal injection is made to obtain approval to engage in the commercial manufacture, use, or sale of the not apply to administration of a drug or device method of execution. State V. Deputy, Del.Su- by a licensed member of medical profession. drug before the expiration of the patent referred to in the certification. Such notice per.1994, 644 A.2d 411. shall include a detailed statement of the factual and legal basis of the applicant's opinion § 355. New drugs that the patent is not valid or will not be infringed. (C) If an application is amended to include a certification described in paragraph (a) Necessity of effective approval of application (2)(A)(iv), the notice required by subparagraph (B) shall be given when the amended No person shall introduce or deliver for introduction into interstate commerce any application is submitted. new drug, unless an approval of an application filed pursuant to subsection (b) or (j) of this section is effective with respect to such drug. (c) Period for approval of application; period for, notice, and expedition of hear- ing; period for issuance of order (b) Filing application; contents (1) Within one hundred and eighty days after the filing of an application under (1) Any person may file with the Secretary an application with respect to any drug subject to the provisions of subsection (a) of this section. Such person shall submit to subsection (b) of this section, or such additional period as may be agreed upon by the Secretary and the applicant, the Secretary shall either- 186 21 § 355 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 (A) Approve the application if he then finds that none of the grounds for denying approval specified in subsection (d) of this section applies, or 28 for a declaratory judgment with respect to the patent. Any action brought (B) Give the applicant notice of an opportunity for a hearing before the Secre- under such section 2201 shall be brought in the judicial district where the defendant tary under subsection (d) of this section on the question whether such application is has its principal place of business or a regular and established place of business. approvable. If the applicant elects to accept the opportunity for hearing by written (D)(i) If an application (other than an abbreviated new drug application) submit- request within thirty days after such notice, such hearing shall commence not more ted under subsection (b) of this section for a drug, no active ingredient (including than ninety days after the expiration of such thirty days unless the Secretary and any ester or salt of the active ingredient) of which has been approved in any other the applicant otherwise agree. Any such hearing shall thereafter be conducted on application under subsection (b) of this section, was approved during the period an expedited basis and the Secretary's order thereon shall be issued within ninety beginning January 1, 1982, and ending on September 24, 1984, the Secretary may days after the date fixed by the Secretary for filing final briefs. not make the approval of another application for a drug for which the investigations (2) If the patent information described in subsection (b) of this section could not be described in clause (A) of subsection (b)(1) of this section and relied upon by the filed with the submission of an application under subsection (b) of this section because applicant for approval of the application were not conducted by or for the applicant the application was filed before the patent information was required under subsection (b) and for which the applicant has not obtained a right of reference or use from the of this section or a patent was issued after the application was approved under such person by or for whom the investigations were conducted effective before the subsection, the holder of an approved application shall file with the Secretary the patent expiration of ten years from the date of the approval of the application previously number and the expiration date of any patent which claims the drug for which the approved under subsection (b) of this section. application was submitted or which claims a method of using such drug and with respect to which a claim of patent infringement could reasonably be asserted if a person not (ii) If an application submitted under subsection (b) of this section for a drug, no licensed by the owner engaged in the manufacture, use, or sale of the drug. If the active ingredient (including any ester or salt of the active ingredient) of which has holder of an approved application could not file patent information under subsection (b) been approved in any other application under subsection (b) of this section, is of this section because it was not required at the time the application was approved, the approved after September 24, 1984, no application which refers to the drug for holder shall file such information under this subsection not later than thirty days after which the subsection (b) application was submitted and for which the investigations September 24, 1984, and if the holder of an approved application could not file patent described in clause (A) of subsection (b)(1) of this section and relied upon by the information under subsection (b) of this section because no patent had been issued when applicant for approval of the application were not conducted by or for the applicant an application was filed or approved, the holder shall file such information under this and for which the applicant has not obtained a right of reference or use from the subsection not later than thirty days after the date the patent involved is issued. Upon person by or for whom the investigations were conducted may be submitted under the submission of patent information under this subsection, the Secretary shall publish subsection (b) of this section before the expiration of five years from the date of the it. approval of the application under subsection (b) of this section, except that such an (3) The approval of an application filed under subsection (b) of this section which application may be submitted under subsection (b) of this section after the expira- tion of four years from the date of the approval of the subsection (b) application if it contains a certification required by paragraph (2) of such subsection shall be made contains a certification of patent invalidity or noninfringement described in clause effective on the last applicable date determined under the following: (iv) of subsection (b)(2)(A) of this section. The approval of such an application shall (A) If the applicant only made a certification described in clause (i) or (ii) of be made effective in accordance with this paragraph except that, if an action for subsection (b)(2)(A) of this section or in both such clauses, the approval may be patent infringement is commenced during the one-year period beginning forty-eight made effective immediately. months after the date of the approval of the subsection (b) application, the thirty- (B) If the applicant made a certification described in clause (iii) of subsection month period referred to in subparagraph (C) shall be extended by such amount of (b)(2)(A) of this section, the approval may be made effective on the date certified time (if any) which is required for seven and one-half years to have elapsed from under clause (iii). the date of approval of the subsection (b) application. (C) If the applicant made a certification described in clause (iv) of subsection (iii) If an application submitted under subsection (b) of this section for a drug, (b)(2)(A) of this section, the approval shall be made effective immediately unless an which includes an active ingredient (including any ester or salt of the active action is brought for infringement of a patent which is the subject of the certifica- ingredient) that has been approved in another application approved under subsec- tion before the expiration of forty-five days from the date the notice provided under tion (b) of this section, is approved after September 24, 1984, and if such application paragraph (3)(B) is received. If such an action is brought before the expiration of contains reports of new clinical investigations (other than bioavailability studies) such days, the approval may be made effective upon the expiration of the thirty- essential to the approval of the application and conducted or sponsored by the month period beginning on the date of the receipt of the notice provided under applicant, the Secretary may not make the approval of an application submitted paragraph (3)(B) or such shorter or longer period as the court may order because under subsection (b) of this section for the conditions of approval of such drug in the either party to the action failed to reasonably cooperate in expediting the action, except that- approved subsection (b) application effective before the expiration of three years from the date of the approval of the application under subsection (b) of this section (i) if before the expiration of such period the court decides that such patent if the investigations described in clause (A) of subsection (b)(1) of this section and is invalid or not infringed, the approval may be made effective on the date of relied upon by the applicant for approval of the application were not conducted by the court decision, or for the applicant and if the applicant has not obtained a right of reference or use (ii) if before the expiration of such period the court decides that such patent from the person by or for whom the investigations were conducted. has been infringed, the approval may be made effective on such date as the (iv) If a supplement to an application approved under subsection (b) of this court orders under section 271(e)(4)(A) of Title 35, or section is approved after September 24, 1984, and the supplement contains reports (iii) if before the expiration of such period the court grants a preliminary of new clinical investigations (other than bioavailability studies) essential to the injunction prohibiting the applicant from engaging in the commercial manufac- approval of the supplement and conducted or sponsored by the person submitting ture or sale of the drug until the court decides the issues of patent validity and the supplement, the Secretary may not make the approval of an application infringement and if the court decides that such patent is invalid or not submitted under subsection (b) of this section for a change approved in the infringed, the approval shall be made effective on the date of such court supplement effective before the expiration of three years from the date of the decision. approval of the supplement under subsection (b) of this section if the investigations In such an action, each of the parties shall reasonably cooperate in expediting the described in clause (A) of subsection (b)(1) of this section and relied upon by the action. Until the expiration of forty-five days from the date the notice made under applicant for approval of the application were not conducted by or for the applicant paragraph (3)(B) is received, no action may be brought under section 2201 of Title and if the applicant has not obtained a right of reference or use from the person by 188 or for whom the investigations were conducted. 21 § 355 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 (v) If an application (or supplement to an application) submitted under subsection tion; or (5) that the at the application contains any untrue statement of a material fact: (b) of this section for a drug, which includes an active ingredient (including any Provided, That if the Secretary (or in his absence the officer acting as Secretary) finds ester or salt of the active ingredient) that has been approved in another application that there is an imminent hazard to the public health, he may suspend the approval of under subsection (b) of this section, was approved during the period beginning such application immediately, and give the applicant prompt notice of his action and January 1, 1982, and ending on September 24, 1984, the Secretary may not make afford the applicant the opportunity for an expedited hearing under this subsection; but the approval of an application submitted under this subsection and for which the the authority conferred by this proviso to suspend the approval of an application shall investigations described in clause (A) of subsection (b)(1) of this section and relied not be delegated. The Secretary may also, after due notice and opportunity for hearing upon by the applicant for approval of the application were not conducted by or for to the applicant, withdraw the approval of an application submitted under subsection (b) the applicant and for which the applicant has not obtained a right of reference or or (j) of this section with respect to any drug under this section if the Secretary finds (1) use from the person by or for whom the investigations were conducted and which that the applicant has failed to establish a system for maintaining required records, or refers to the drug for which the subsection (b) application was submitted effective has repeatedly or deliberately failed to maintain such records or to make required before the expiration of two years from September 24, 1984. reports, in accordance with a regulation or order under subsection (k) of this section or to comply with the notice requirements of section 360(k)(2) of this title, or the applicant (d) Grounds for refusing application; approval of application; "substantial evi- has refused to permit access to, or copying or verification of, such records as required by dence" defined paragraph (2) of such subsection; or (2) that on the basis of new information before him, If the Secretary finds, after due notice to the applicant in accordance with subsection evaluated together with the evidence before him when the application was approved, the (c) of this section and giving him an opportunity for a hearing, in accordance with said methods used in, or the facilities and controls used for, the manufacture, processing, and subsection, that (1) the investigations, reports of which are required to be submitted to packing of such drug are inadequate to assure and preserve its identity, strength, the Secretary pursuant to subsection (b) of this section, do not include adequate tests by quality, and purity and were not made adequate within a reasonable time after receipt of all methods reasonably applicable to show whether or not such drug is safe for use written notice from the Secretary specifying the matter complained of; or (3) that on the under the conditions prescribed, recommended, or suggested in the proposed labeling basis of new information before him, evaluated together with the evidence before him thereof; (2) the results of such tests show that such drug is unsafe for use under such when the application was approved, the labeling of such drug, based on a fair evaluation conditions or do not show that such drug is safe for use under such conditions; (3) the of all material facts, is false or misleading in any particular and was not corrected within methods used in, and the facilities and controls used for, the manufacture, processing, a reasonable time after receipt of written notice from the Secretary specifying the and packing of such drug are inadequate to preserve its identity, strength, quality, and matter complained of. Any order under this subsection shall state the findings upon purity; (4) upon the basis of the information submitted to him as part of the application, which it is based. or upon the basis of any other information before him with respect to such drug, he has insufficient information to determine whether such drug is safe for use under such [See main volume for text of (f) to (i)] conditions; or (5) evaluated on the basis of the information submitted to him as part of (j) Abbreviated new drug applications the application and any other information before him with respect to such drug, there is a lack of substantial evidence that the drug will have the effect it purports or is (1) Any person may file with the Secretary an abbreviated application for the represented to have under the conditions of use prescribed, recommended, or suggested approval of a new drug. in the proposed labeling thereof; or (6) the application failed to contain the patent (2)(A) An abbreviated application for a new drug shall contain- information prescribed by subsection (b) of this section; or (7) based on a fair evaluation (i) information to show that the conditions of use prescribed, recommended, or of all material facts, such labeling is false or misleading in any particular; he shall issue suggested in the labeling proposed for the new drug have been previously approved an order refusing to approve the application. If, after such notice and opportunity for for a drug listed under paragraph (6) (hereinafter in this subsection referred to as a hearing, the Secretary finds that clauses (1) through (6) do not apply, he shall issue an "listed drug"); order approving the application. As used in this subsection and subsection (e) of this section, the term "substantial evidence" means evidence consisting of adequate and well- (ii)(I) if the listed drug referred to in clause (i) has only one active ingredient, controlled investigations, including clinical investigations, by experts qualified by scienti- information to show that the active ingredient of the new drug is the same as that of the listed drug; fic training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly and responsibly be concluded by such experts that the drug (II) if the listed drug referred to in clause (i) has more than one active will have the effect it purports or is represented to have under the conditions of use ingredient, information to show that the active ingredients of the new drug are the prescribed, recommended, or suggested in the labeling or proposed labeling thereof. same as those of the listed drug, or (III) if the listed drug referred to in clause (i) has more than one active (e) Withdrawal of approval; grounds; immediate suspension upon finding immi- ingredient and if one of the active ingredients of the new drug is different and the nent hazard to public health application is filed pursuant to the approval of a petition filed under subparagraph The Secretary shall, after due notice and opportunity for hearing to the applicant, (C), information to show that the other active ingredients of the new drug are the withdraw approval of an application with respect to any drug under this section if the same as the active ingredients of the listed drug, information to show that the Secretary finds (1) that clinical or other experience, tests, or other scientific data show different active ingredient is an active ingredient of a listed drug or of a drug which that such drug is unsafe for use under the conditions of use upon the basis of which the does not meet the requirements of section 321(p) of this title, and such other application was approved; (2) that new evidence of clinical experience, not contained in information respecting the different active ingredient with respect to which the such application or not available to the Secretary until after such application was petition was filed as the Secretary may require; approved, or tests by new methods, or tests by methods not deemed reasonably (iii) information to show that the route of administration, the dosage form, and applicable when such application was approved, evaluated together with the evidence the strength of the new drug are the same as those of the listed drug referred to in available to the Secretary when the application was approved, shows that such drug is clause (i) or, if the route of administration, the dosage form, or the strength of the not shown to be safe for use under the conditions of use upon the basis of which the new drug is different and the application is filed pursuant to the approval of a application was approved; or (3) on the basis of new information before him with respect petition filed under subparagraph (C), such information respecting the route of to such drug, evaluated together with the evidence available to him when the application administration, dosage form, or strength with respect to which the petition was filed was approved, that there is a lack of substantial evidence that the drug will have the as the Secretary may require; effect it purports or is represented to have under the conditions of use prescribed, (iv) information to show that the new drug is bioequivalent to the listed drug recommended, or suggested in the labeling thereof; or (4) the patent information referred to in clause (i), except that if the application is filed pursuant to the prescribed by subsection (c) of this section was not filed within thirty days after the approval of a petition filed under subparagraph (C), information to show that the receipt of written notice from the Secretary specifying the failure to file such informa- active ingredients of the new drug are of the same pharmacological or therapeutic 190 21 $ 355 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 class as those of the listed drug referred to in clause (i) and the new drug can be expected to have the same therapeutic effect as the listed drug when administered (A) the methods used in, or the facilities and controls used for, the manufacture, to patients for a condition of use referred to in clause (i); processing, and packing of the drug are inadequate to assure and preserve its (v) information to show that the labeling proposed for the new drug is the same identity, strength, quality, and purity; as the labeling approved for the listed drug referred to in clause (i) except for (B) information submitted with the application is insufficient to show that each of changes required because of differences approved under a petition filed under the proposed conditions of use have been previously approved for the listed drug subparagraph (C) or because the new drug and the listed drug are produced or referred to in the application; distributed by different manufacturers; (C)(i) if the listed drug has only one active ingredient, information submitted (vi) the items specified in clauses (B) through (F) of subsection (b)(1) of this with the application is insufficient to show that the active ingredient is the same as section; that of the listed drug; (vii) a certification, in the opinion of the applicant and to the best of his (ii) if the listed drug has more than one active ingredient, information submitted knowledge, with respect to each patent which claims the listed drug referred to in with the application is insufficient to show that the active ingredients are the same clause (i) or which claims a use for such listed drug for which the applicant is as the active ingredients of the listed drug, or seeking approval under this subsection and for which information is required to be (iii) if the listed drug has more than one active ingredient and if the application filed under subsection (b) or (c) of this section- is for a drug which has an active ingredient different from the listed drug, (I) that such patent information has not been filed, information submitted with the application is insufficient to show- (II) that such patent has expired, (I) that the other active ingredients are the same as the active ingredients of the listed drug, or (III) of the date on which such patent will expire, or (II) that the different active ingredient is an active ingredient of a listed (IV) that such patent is invalid or will not be infringed by the manufacture, drug or a drug which does not meet the requirements of section 321(p) of this use, or sale of the new drug for which the application is submitted; and title, (viii) if with respect to the listed drug referred to in clause (i) information was or no petition to file an application for the drug with the different ingredient filed under subsection (b) or (c) of this section for a method of use patent which was approved under paragraph (2)(C); does not claim a use for which the applicant is seeking approval under this subsection, a statement that the method of use patent does not claim such a use. (D)(i) if the application is for a drug whose route of administration, dosage form, or strength of the drug is the same as the route of administration, dosage form, or The Secretary may not require that an abbreviated application contain information in strength of the listed drug referred to in the application, information submitted in addition to that required by clauses (i) through (viii). the application is insufficient to show that the route of administration, dosage form, (B)(i) An applicant who makes a certification described in subparagraph (A)(vii)(IV) or strength is the same as that of the listed drug, or shall include in the application a statement that the applicant will give the notice (ii) if the application is for a drug whose route of administration, dosage form, or required by clause (ii) to- strength of the drug is different from that of the listed drug referred to in the (I) each owner of the patent which is the subject of the certification or the application, no petition to file an application for the drug with the different route of representative of such owner designated to receive such notice, and administration, dosage form, or strength was approved under paragraph (2)(C); (II) the holder of the approved application under subsection (b) of this section for (E) if the application was filed pursuant to the approval of a petition under the drug which is claimed by the patent or a use of which is claimed by the patent paragraph (2)(C), the application did not contain the information required by the or the representative of such holder designated to receive such notice. Secretary respecting the active ingredient, route of administration, dosage form, or (ii) The notice referred to in clause (i) shall state that an application, which contains strength which is not the same; data from bioavailability or bioequivalence studies, has been submitted under this (F) information submitted in the application is insufficient to show that the drug subsection for the drug with respect to which the certification is made to obtain approval is bioequivalent to the listed drug referred to in the application or, if the application to engage in the commercial manufacture, use, or sale of such drug before the expiration was filed pursuant to a petition approved under paragraph (2)(C), information of the patent referred to in the certification. Such notice shall include a detailed submitted in the application is insufficient to show that the active ingredients of the statement of the factual and legal basis of the applicant's opinion that the patent is not new drug are of the same pharmacological or therapeutic class as those of the listed valid or will not be infringed. drug referred to in paragraph (2)(A)(i) and that the new drug can be expected to have the same therapeutic effect as the listed drug when administered to patients (iii) If an application is amended to include a certification described in subparagraph (A)(vii)(IV), the notice required by clause (ii) shall be given when the amended for a condition of use referred to in such paragraph; application is submitted. (G) information submitted in the application is insufficient to show that the labeling proposed for the drug is the same as the labeling approved for the listed (C) If a person wants to submit an abbreviated application for a new drug which has drug referred to in the application except for changes required because of differ- a different active ingredient or whose route of administration, dosage form, or strength ences approved under a petition filed under paragraph (2)(C) or because the drug differ from that of a listed drug, such person shall submit a petition to the Secretary and the listed drug are produced or distributed by different manufacturers; seeking permission to file such an application. The Secretary shall approve or disap- (H) information submitted in the application or any other information available to prove a petition submitted under this subparagraph within ninety days of the date the the Secretary shows that (i) the inactive ingredients of the drug are unsafe for use finds- petition is submitted. The Secretary shall approve such a petition unless the Secretary under the conditions prescribed, recommended, or suggested in the labeling pro- posed for the drug, or (ii) the composition of the drug is unsafe under such (i) that investigations must be conducted to show the safety and effectiveness of conditions because of the type or quantity of inactive ingredients included or the the drug or of any of its active ingredients, the route of administration, the dosage manner in which the inactive ingredients are included; form, or strength which differ from the listed drug; or (I) the approval under subsection (c) of this section of the listed drug referred to (ii) that any drug with a different active ingredient may not be adequately in the application under this subsection has been withdrawn or suspended for evaluated for approval as safe and effective on the basis of the information required grounds described in the first sentence of subsection (e) of this section, the to be submitted in an abbreviated application. Secretary has published a notice of opportunity for hearing to withdraw approval of (3) Subject to paragraph (4), the Secretary shall approve an application for a drug the listed drug under subsection (c) of this section for grounds described in the first unless the Secretary finds— sentence of subsection (e) of this section, the approval under this subsection of the 192 listed drug referred to in the application under this subsection has been withdrawn 193 21 § 355 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 or suspended under paragraph (5), or the Secretary has determined that the listed Secretary and the applicant otherwise agree. Any such hearing shall thereafter be drug has been withdrawn from sale for safety or effectiveness reasons; conducted on an expedited basis and the Secretary's order thereon shall be issued within (J) the application does not meet any other requirement of paragraph (2)(A); or ninety days after the date fixed by the Secretary for filing final briefs. (K) the application contains an untrue statement of material fact. (D)(i) If an application (other than an abbreviated new drug application) submitted (4)(A) Within one hundred and eighty days of the initial receipt of an application under subsection (b) of this section for a drug, no active ingredient (including any ester under paragraph (2) or within such additional period as may be agreed upon by the or salt of the active ingredient) of which has been approved in any other application Secretary and the applicant, the Secretary shall approve or disapprove the application. under subsection (b) of this section, was approved during the period beginning January 1, 1982, and ending on September 24, 1984, the Secretary may not make the approval of (B) The approval of an application submitted under paragraph (2) shall be. made an application submitted under this subsection which refers to the drug for which the effective on the last applicable date determined under the following: subsection (b) application was submitted effective before the expiration of ten years from (i) If the applicant only made a certification described in subclause (I) or (II) of the date of the approval of the application under subsection (b) of this section. paragraph (2)(A)(vii) or in both such subclauses, the approval may be made effective (ii) If an application submitted under subsection (b) of this section for a drug, no immediately. active ingredient (including any ester or salt of the active ingredient) of which has been (ii) If the applicant made a certification described in subclause (III) of paragraph approved in any other application under subsection (b) of this section, is approved after (2)(A)(vii), the approval may be made effective on the date certified under subclause September 24, 1984, no application may be submitted under this subsection which refers (III). to the drug for which the subsection (b) application was submitted before the expiration (iii) If the applicant made a certification described in subclause (IV) of para- of five years from the date of the approval of the application under subsection (b) of this graph (2)(A)(vii), the approval shall be made effective immediately unless an action section, except that such an application may be submitted under this subsection after the is brought for infringement of a patent which is the subject of the certification expiration of four years from the date of the approval of the subsection (b) application if before the expiration of forty-five days from the date the notice provided under it contains a certification of patent invalidity or noninfringement described in subclause paragraph (2)(B)(i) is received. If such an action is brought before the expiration of (IV) of paragraph (2)(A)(vii). The approval of such an application shall be made such days, the approval shall be made effective upon the expiration of the thirty- effective in accordance with subparagraph (B) except that, if an action for patent month period beginning on the date of the receipt of the notice provided under infringement is commenced during the one-year period beginning forty-eight months paragraph (2)(B)(i) or such shorter or longer period as the court may order because after the date of the approval of the subsection (b) application, the thirty-month period either party to the action failed to reasonably cooperate in expediting the action, referred to in subparagraph (B)(iii) shall be extended by such amount of time (if any) except that- which is required for seven and one-half years to have elapsed from the date of approval (I) if before the expiration of such period the court decides that such patent of the subsection (b) application. is invalid or not infringed, the approval shall be made effective on the date of (iii) If an application submitted under subsection (b) of this section for a drug, which the court decision, includes an active ingredient (including any ester or salt of the active ingredient) that (II) if before the expiration of such period the court decides that such patent has been approved in another application approved under subsection (b) of this section, has been infringed, the approval shall be made effective on such date as the is approved after September 24, 1984, and if such application contains reports of new court orders under section 271(e)(4)(A) of Title 35 or clinical investigations (other than bioavailability studies) essential to the approval of the (III) if before the expiration of such period the court grants a preliminary application and conducted or sponsored by the applicant, the Secretary may not make injunction prohibiting the applicant from engaging in the commercial manufac- the approval of an application submitted under this subsection for the conditions of ture or sale of the drug until the court decides the issues of patent validity and approval of such drug in the subsection (b) application effective before the expiration of infringement and if the court decides that such patent is invalid or not three years from the date of the approval of the application under subsection (b) of this infringed, the approval shall be made effective on the date of such court section for such drug. decision. (iv) If a supplement to an application approved under subsection (b) of this section is In such an action, each of the parties shall reasonably cooperate in expediting approved after September 24, 1984, and the supplement contains reports of new clinical the action. Until the expiration of forty-five days from the date the notice investigations (other than bioavailability studies) essential to the approval of the made under paragraph (2)(B)(i) is received, no action may be brought under supplement and conducted or sponsored by the person submitting the supplement, the section 2201 of Title 28 for a declaratory judgment with respect to the patent. Secretary may not make the approval of an application submitted under this subsection Any action brought under section 2201 shall be brought in the judicial district for a change approved in the supplement effective before the expiration of three years where the defendant has its principal place of business or a regular and from the date of the approval of the supplement under subsection (b) of this section. established place of business. (v) If an application (or supplement to an application) submitted under subsection (b) (iv) If the application contains a certification described in subclause (IV) of of this section for a drug, which includes an active ingredient (including any ester or salt paragraph (2)(A)(vii) and is for a drug for which a previous application has been of the active ingredient) that has been approved in another application under subsection submitted under this subsection continuing such a certification, the application shall (b) of this section, was approved during the period beginning January 1, 1982, and be made effective not earlier than one hundred and eighty days after- ending. on September 24, 1984, the Secretary may not make the approval of an (I) the date the Secretary receives notice from the applicant under the application submitted under this subsection which refers to the drug for which the previous application of the first commercial marketing of the drug under the subsection (b) application was submitted or which refers to a change approved in a previous application, or supplement to the subsection (b) application effective before the expiration of two years (II) the date of a decision of a court in an action described in clause (iii) from September 24, 1984. holding the patent which is the subject of the certification to be invalid or not (5) If a drug approved under this subsection refers in its approved application to a infringed, drug the approval of which was withdrawn or suspended for grounds described in the whichever is earlier. first sentence of subsection (e) of this section or was withdrawn or suspended under this (C) If the Secretary decides to disapprove an application, the Secretary shall give the paragraph or which, as determined by the Secretary, has been withdrawn from sale for applicant notice of an opportunity for a hearing before the Secretary on the question of safety or effectiveness reasons, the approval of the drug under this subsection shall J be whether such application is approvable. If the applicant elects to accept the opportunity withdrawn or suspended- for hearing by written request within thirty days after such notice, such hearing shall (A) for the same period as the withdrawal or suspension under subsection ed commence not more than ninety days after the expiration of such thirty days unless the this section or this paragraph, or 194 195 21 § 355 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 (B) if the listed drug has been withdrawn from sale, for the period of withdrawal (C) the name of each person to whom the review of the chemistry of the from sale or, if earlier, the period ending on the date the Secretary determines that application was assigned and the date of such assignment, and the withdrawal from sale is not for safety or effectiveness reasons. (D) the name of each person to whom the bioequivalence review for such (6)(A)(i) Within sixty days of September 24, 1984, the Secretary shall publish and application was assigned and the date of such assignment. make available to the public- The information the Secretary is required to maintain under this paragraph with respect (I) a list in alphabetical order of the official and proprietary name of each drug to an application submitted under this subsection shall be made available to the public which has been approved for safety and effectiveness under subsection (c) of this after the approval of such application. section before September 24, 1984; (II) the date of approval if the drug is approved after 1981 and the number of the (k) Records and reports; required information; regulations and orders; access to application which was approved; and records (III) whether in vitro or in vivo bioequivalence studies, or both such studies, are (1) In the case of any drug for which an approval of an application filed under required for applications filed under this subsection which will refer to the drug subsection (b) or (j) of this section is in effect, the applicant shall establish and maintain published. such records, and make such reports to the Secretary, of data relating to clinical experience and other data or information, received or otherwise obtained by such (ii) Every thirty days after the publication of the first list under clause (i) the applicant with respect to such drug, as the Secretary may by general regulation, or by Secretary shall revise the list to include each drug which has been approved for safety order with respect to such application, prescribe on the basis of a finding that such and effectiveness under subsection (c) of this section or approved under this subsection records and reports are necessary in order to enable the Secretary to determine, or during the thirty-day period. facilitate a determination, whether there is or may be ground for invoking subsection (e) (iii) When patent information submitted under subsection (b) or (c) of this section of this section. Regulations and orders issued under this subsection and under respecting a drug included on the list is to be published by the Secretary, the Secretary subsection (i) of this section shall have due regard for the professional ethics of the shall, in revisions made under clause (ii), include such information for such drug. medical profession and the interests of patients and shall provide, where the Secretary deems it to be appropriate, for the examination, upon request, by the persons to whom (B) A drug approved for safety and effectiveness under subsection (c) of this section such regulations or orders are applicable, of similar information received or otherwise or approved under this subsection shall, for purposes of this subsection, be considered to obtained by the Secretary. have been published under subparagraph (A) on the date of its approval or September 24, 1984, whichever is later. (2) Every person required under this section to maintain records, and every person in charge or custody thereof, shall, upon request of an officer or employee designated by (C) If the approval of a drug was withdrawn or suspended for grounds described in the Secretary, permit such officer or employee at all reasonable times to have access to the first sentence of subsection (e) of this section or was withdrawn or suspended under and copy and verify such records. paragraph (5) or if the Secretary determines that a drug has been withdrawn from sale for safety or effectiveness reasons, it may not be published in the list under subpara- (I) Public disclosure of safety and effectiveness data graph (A) or, if the withdrawal or suspension occurred after its publication in such list, it shall be immediately removed from such list— Safety and effectiveness data and information which has been submitted in an application under subsection (b) of this section for a drug and which has not previously (i) for the same period as the withdrawal or suspension under subsection (e) of been disclosed to the public shall be made available to the public, upon request, unless this section or paragraph (5), or extraordinary circumstances are shown- (ii) if the listed drug has been withdrawn from sale, for the period of withdrawal (1) if no work is being or will be undertaken to have the application approved, from sale or, if earlier, the period ending on the date the Secretary determines that the withdrawal from sale is not for safety or effectiveness reasons. (2) if the Secretary has determined that the application is not approvable and all legal appeals have been exhausted, A notice of the removal shall be published in the Federal Register. (3) if approval of the application under subsection (c) of this section is withdrawn (7) For purposes of this subsection: and all legal appeals have been exhausted, (A) The term "bioavailability" means the rate and extent to which the active (4) if the Secretary has determined that such drug is not a new drug, or ingredient or therapeutic ingredient is absorbed from a drug and becomes available (5) upon the effective date of the approval of the first application under subsec- at the site of drug action. tion (j) of this section which refers to such drug or upon the date upon which the (B) A drug shall be considered to be bioequivalent to a listed drug if- approval of an application under subsection (j) of this section which refers to such (i) the rate and extent of absorption of the drug do not show a significant drug could be made effective if such an application had been submitted. difference from the rate and extent of absorption of the listed drug when (m) "Patent" defined administered at the same molar dose of the therapeutic ingredient under similar experimental conditions in either a single dose or multiple doses; or For purposes of this section, the term "patent" means a patent issued by the Patent (ii) the extent of absorption of the drug does not show a significant and Trademark Office of the Department of Commerce. difference from the extent of absorption of the listed drug when administered (As amended Aug. 16, 1972, Pub.L. 92-387, § 4(d), 86 Stat. 562; Sept. 24, 1984, Pub.L. 98-417, Title at the same molar dose of the therapeutic ingredient under similar experimen- I, §§ 101, 102(a)-(b)(5), 103, 104, 98 Stat. 1585, 1592, 1593, 1597; May 13, 1992, Pub.L. 102-282, § 5, tal conditions in either a single dose or multiple doses and the difference from 106 Stat. 161; Aug. 13, 1993, Pub.L. 103-80, $ 3(n), 107 Stat. 777.) the listed drug in the rate of absorption of the drug is intentional, is reflected in its proposed labeling, is not essential to the attainment of effective body drug HISTORICAL AND STATUTORY NOTES concentrations on chronic use, and is considered medically insignificant for the 1993 Amendments Subsec. (k)(1). Pub.L. 103-80, $ 3(n)(2), drug. Subsec. (j)(6)(A)(ii). Pub.L. 103-80, struck out ": Provided, however, That regula- § 3(n)(1)(A), corrected a typographical error in tions" and inserted in lieu thereof a period and (8) The Secretary shall, with respect to each application submitted under this the original by substituting "Secretary" for "Regulations". subsection, maintain a record of- "Secretry". 1992 Amendments (A) the name of the applicant, Subsec. (j)(6)(A)(iii). Pub.L. 103-80, § 3(n)(1)(B), inserted a comma after "published Subsec. (j)(8). Pub.L. 102-282, $ 5, added (B) the name of the drug covered by the application, by the Secretary". par. (8). 196 197 21 8 355 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 1984 Amendment of this section or to comply with the notice Subsec. (a). Pub.L. 98-417, $ 102(b)(1), add- requirements of section 360(j)(2) of this title". for any drug which has been approved for safety 16, 1972, see section 5 of Pub.L. 92-387, set out ed "or (j)" following "pursuant to subsection Subsec. (j). Pub.L. 98-417, § 101, added sub- and effectiveness under section 505(c) of the as a note under section 360 of this title. (b)". sec. (j). Former subsec. (j) was redesignated Federal Food, Drug, and Cosmetic Act [subsec. Subsec. (b)(1). Pub.L. 98-417, $ 103(a), des- (k). (c) of this section] before the date of the enact- Federal Policy Regarding the Export of ment of this Act [Sept. 24, 1984]. If any such Banned or Significantly Restricted Sub- ignated the existing provisions of subsec. (b) as Subsec. (k). Pub.L. 98-417, $ 101, redesig- nated former subsec. (j) as (k). provision is inconsistent with the requirements stances par. (1) thereof and redesignated existing cls. (1) through (6) of par. (1) as 60 redesignated as cls. of section 505(j) of the Federal Food, Drug, and For provisions relating to the applicability of (A) through (F) thereof, respectively. Subsec. (k)(1). Pub.L. 98-417, 1 102(b)(5), Cosmetic Act [subsec. (j) of this section], the the term "banned or significantly restricted sub- substituted "under subsection (b) or (j) of this Pub.L. 98-417, $ 102(a)(1), added requirement Secretary shall consider the application under stance", as defined, and the Federal policy re- section" for "pursuant to this section". that the applicant file with the application the the applicable requirements of such section. garding the export of banned or significantly patent number and the expiration date of any Subsecs. (l), (m). Pub.L. 98-417, $ 104, add- The Secretary of Health and Human Services restricted substances, see section 1-101 of Ex. ed subsecs. (l) and (m). patent which claims the drug for which the may not approve such an abbreviated new drug Ord. No. 12264, Jan. 15, 1981, 46 F.R. 4659, set applicant submitted the application or which application which is filed for a drug which is out as a note under section 2403 of Title 50, 1972 Amendment described in sections 505(c)(3)(D) and claims a method of using such drug and with Appendix, War and National Defense. Subsec. (e). Pub.L. 92-387 inserted "or to respect to which a claim of patent infringement 505(j)(4)(D) of the Federal Food, Drug, and comply with the notice requirements of section could reasonably be asserted if a person not Cosmetic Act [subsecs. (c)(8)(D) and (j)(4)(D) of Legislative History 360(j) (2)' in clause (1) of the second sentence licensed by the owner engaged in the manufac- this section], except in accordance with such For legislative history and purpose of Pub.L. relating to the maintenance of records. ture, use, or sale of the drug, that the applicant section." 92-387, see 1972 U.S. Code Cong. and Adm. amend the application to include such informa- Change of Name News, p. 2963. See, also, Pub.L. 98-417, 1984 Effective Date of 1972 Amendment tion if an application is filed under this subsec- The Department of Health, Education, and U.S. Code Cong. and Adm. News, p. 2647; tion for a drug and a patent which claims such Welfare was redesignated the Department of Amendment by Pub.L. 92-887 effective on the Pub.L. 102-282, 1992 U.S. Code Cong. and Adm. drug or a method of using such drug is issued Health and Human Services, and the Secretary first day of the sixth month beginning after Aug. News, p. 103. after the filing date but before approval of the of Health, Education, and Welfare or any other application, and that, upon approval of the appli- CROSS REFERENCES official of the Department of Health, Education cation, the Secretary, publish the information submitted. and Welfare was redesignated the Secretary or Patents, extension of patent term, see 35 official, as appropriate, of Health and Human USCA $ 156. Subsec. (b)(2), (3). Pub.L. 98-417, § 103(a), Services, with any reference to the Department added pars. (2) and (8). of Health, Education, and Welfare, the Secre- FEDERAL PRACTICE AND PROCEDURE Subsec. (c)(1): Pub.L. 98-417, § 102(a)(2), tary of Health, Education, and Welfare, or any Review of administrative decisions in courts of designated the existing provisions of subsec. (c) official of the Department of Health, Education, appeals, see Wright, Miller, Cooper & Gress- as par. (1) thereof and in par. (1) as 80 designat- and Welfare, in any law, rule, regulation, certifi- man: Jurisdiction $ 3941. ed redesignated former pars. (1) and (2) as cate, directive, instruction, or other official pa- subpars. (A) and (B), respectively. per in force on the effective date of Pub.L. WESTS FEDERAL PRACTICE MANUAL Pub.L. 98-417, $ 102(b)(2), substituted "sub- 96-88, as prescribed by section 601 of Pub.L. 96-88, Title VI, Oct. 17, 1979, 93 Stat. 696, set Application for use of new drug, see $ 3638. section (b) of this section" for "this subsection". Subsec. (c)(2). Pub.L. 98-417, $ 102(a)(2), out as a note under section 3401 of Title 20, added par. (2). Education, deemed to refer and apply to the CODE OF FEDERAL REGULATIONS Department of Health and Human Services or Formal evidentiary public hearing, see 21 New animal feed drugs, see 21 CFR 558.3. Subsec. (c)(3). Pub.L. 98-417, § 103(b), add- the Secretary of Health and Human Services, CFR 12.1 et seq. New drugs for human use, see 21 CFR ed par. (8). respectively, except to the extent such reference New animal drugs, see 21 CFR 510.3. 310.100 et seq. Subsec. (d)(6). Pub.L. 98-417, § 102(a)(3)(A), is to a function or office transferred to the added cl. (6) relating to the failure of the appli- Secretary of Education or the Department of LAW REVIEW COMMENTARIES cation to contain the patent information pre- Education under Pub.L. 96-88, Title III, §§ 301 A survey of law regarding the liability of Getting new drugs to people with AIDS: A scribed by subsec. (b) of this section. Former to 307, Oct. 17 1979, 93 Stat. 677 to 681. See cl. (6) was redesignated (7). section 3441 to 3447 and 3508 of Title 20. manufacturers and sellers of drug products and public policy response to Lansdale. Marsha N. medical devices. Bryan J. Maedgen and Sheree Cohen, 18 Hastings Const.L.Q. 471 (1991). Subsec. (d)(7). Pub.L. 98-417, $ 102(a)(3)(A), Effective Date of 1984 Amendment Lynn McCall, 18 St. Mary's L.J. 395 (1986). redesignated former cl. (6) as (7). Long-range planning in environmental and Section 105 of Pub.L. 98-417 provided that: Subsec. (e). Pub.L. 98-417, $ 102(a)(3)(B), Brother can you spare a drug: Should the health regulatory agencies. Richard N.L. An- added, in the first sentence covering the "(a) The Secretary of Health and Human experimental drug distribution standards be drews, 20 Ecology L.Q. 515 (1993). grounds for withdrawal of approval by the Sec- Services shall promulgate, in accordance with modified in response to the needs of persons retary, a new cl. (4) relating to the failure to file the notice and comment requirements of section More gold and more fleece: Improving the with Aids? 19 Hofstra L.Rev. 191 (1990). 553 of title 5, United States Code [section 553 of legal sanctions against medical research fraud. the patent information prescribed by subsec. (c) of this section within 30 days after the receipt of Title 5, Government Organization and Employ- Developing, testing, and marketing an AIDS James T. O'Reilly, 42 Admin.L.Rev. 393 (1990). written notice from the Secretary specifying the ees], such regulations as may be necessary for vaccine: Legal concerns for manufacturers. OMB involvement in FDA drug regulations: failure to file such information, and redesignated the administration of section 505 of the Federal Alison Joy Arnold, 139 U.Pa.L.Rev. 1077 (1991). Regulating the regulators. Comment, 38 Catho- the former cl. (4) as (5). Food, Drug, and Cosmetic Act [this section], as amended by sections 101, 102, and 103 of this Drug Price Competition and Patent Term lic U.L.Rev. 175 (1988). Pub.L. 98-417, § 102(b)(3), inserted, in the Act [enacting subsec. (j) of this section and Restoration Act of 1984: Is it a healthy long Right of privacy in choosing medical treat- provisions of the second sentence preceding cl. amending subsecs. (a) to (e) and (k)(1) of this term solution? Note, 21 Rutgers L.J. 147 ment: Should terminally ill persons have access (1) of the enumeration of clauses covering the section and section 360cc(a) and (b) of this title], (1989). to drugs not yet approved by the Food and grounds for withdrawal of approval by the Sec- within one year of the date of enactment of this From dog food to prescription drug advertis- Drug Administration? 20 John Marshall L.Rev. retary, the phrase "submitted under subsection Act [Sept. 24, 1984]. ing: Litigating false scientific establishment 696 (1987). (b) or (j) of this section" after "withdraw the "(b) During the period beginning sixty days claims under the Lanham Act. Charles J. approval of an application". The Drug Price Competition and Patent Term after the date of the enactment of this Act [Sept. Walsh and Marc S. Klein, 22 Seton Hall L.Rev. Restoration Act of 1984. James J. Wheaton, 35 Pub.L. 98-417, § 102(b)(4), substituted, in cl. 24, 1984], and ending on the date regulations 389 (1992). Catholic U.L.Rev. 433 (1986). (1) of the second sentence covering the grounds promulgated under subsection (a) take effect, for withdrawal of approval by the Secretary, the phrase "under subsection (k) of this section or to abbreviated new drug applications may be sub- LIBRARY REFERENCES mitted in accordance with the provisions of sec- comply with the notice requirements of section tion 314.2 of title 21 of the Code of Federal Regulation of drugs and pharmacists general- Regulation of drugs and pharmacists general- 360(k)(2) of this title" for "under subsection (j) Regulations and shall be considered as suitable ly, see Drugs and Narcotics & 1, 11, et seq. ly, see C.J.S. Drugs and Narcotics $ 27 et 198 seq. 100 21 8 355 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 Note 4a NOTES OF DECISIONS Generally 5a be read with provision of this section requiring a 4a. Retroactive effect 2. Construction Active ingredient 9c new drug application to contain a full description Even if a substance is also a food, it may be of methods used in, and facilities and controls Drug, with respect to which a new drug appli- Admissibility of evidence 22a Application, cancellation of 6a subjected to requirements of this chapter if it is used for, manufacture, processing, and packing cation had been filed under this chapter as Approval of drug used in the diagnosis, cure, mitigation, treat- of drug and, as 80 read, should be construed as originally enacted which permitted evaluation of Timeliness 15a ment or prevention of diseases in man or other requiring premarketing approval for a new drug a new drug solely on grounds of unsafety, was Authority of Secretary 5c animals; intended use is an important aspect in product of any manufacturer even if product not exempt from 1962 amendments to this chap- Breast implants 13b determining whether the substance is a drug. purports to be a generic or "me-too" copy of a ter, which directs the Food and Drug Adminis- Clinical studies 13a Rutherford V. U.S., C.A.Okl.1976, 542 F.2d 1137, recognized drug. Pharmadyne Laboratories, tration to withdraw any prior approval if sub- Components 9a on remand 424 F.Supp. 105. Inc. V. Kennedy, D.C.N.J.1979, 466 Supp. 100, stantial evidence that the drug is effective for its Declaratory judgment 29 A consistent construction of this chapter by affirmed 596 F.2d 568. intended use is lacking, by virtue of "grandfa- Issues which were presented in complaint ther clause" of 1962 amendments to this chapter, Defenses 7b the Food and Drug Administration for 30 years Discretion of court 18a and a construction which accords with the literal challenging Food and Drug Administration's ad- notwithstanding contention that when drug be- came generally recognized as safe and was no Drugs administered by physicians 31 language of this chapter may only be changed ministering of this section and section 357 of this longer a "new drug," its new drug application Exclusive marketing period 9b by Congress itself. USV Pharmaceutical Corp. title, governing withdrawal of approval of antibi- ceased to be effective. Weinberger V. Hynson, Exemptions 7a V. Richardson, C.A.Va.1972, 461 F.2d 223, af- otic and nonantibiotic drugs upon finding of lack Westcott and Dunning, Inc., Va.1973, 93 S.Ct. Exhaustion of remedies 6b firmed 93 S.Ct. 2498, 412 U.S. 655, 87 L.Ed.2d of substantial evidence that the drugs have ef- 2469, 412 U.S. 609, 37 L.Ed.2d 207. Insurance 16a 244. fect they are represented to have under condi- Investigatory drugs 35 New drug provisions must be construed tions of use prescribed, recommended or sug- This section contemplates that drugs whose Jurisdiction 17a broadly to meet congressional purpose to keep gested in labeling, and which did not deal with new drug applications became effective prior to Labeling information 36 inadequately tested medical and related prod- agency discretion were subject to review under adoption thereof will be on basis of adequate and Notes of approval 32 ucts which might cause widespread danger to the Administrative Procedure Act, sections 551 well-controlled investigations; withdrawal pro- Offenses within section 5b human life out of interstate commerce. U.S. V. et seq. and 701 et seq. of Title 5. American ceedings cannot be thwarted by a showing of Opinion letters 32a General Nutrition, Inc., W.D.N.Y.1986, 638 Public Health Ass'n V. Veneman, D.C.D.C.1972, general recognition of effectiveness based mere- Prescription drugs 30 F.Supp. 556. 349 F.Supp. 1811. ly on expert testimony and reports with respect Reapplication 6c to investigations and clinical observations re- Definition of "new drug," within meaning of 4. Purpose Remand 34 gardless of the controls used. Weinberger V. Remedy 33 this section, which provided that such drugs In enacting 1962 amendments to this chapter Hynson, Westcott and Dunning, Inc., Va.1973, could not be marketed prior to approval by Food Retroactive effect 4a which direct Food and Drug Administration to 98 S.Ct. 2469, 412 U.S. 609, 87 L.Ed.2d 207. Review 28 and Drug Administration of either new drug refuse approval for a new drug application and Standards of review 28a application or abbreviated new drug application, to withdraw any prior approval if substantial Efficacy requirements of this section were not must be liberally construed in order to effectu- Summary judgment 27 evidence that drug is effective for its intended designed to be prospective only. Weinberger V. ate policy of this chapter, which is protection of use is lacking, Congress intended test for estab- Hynson, Westcott and Dunning, Inc., Va.1973, Timeliness, approval of drug 15a public health and safety. U.S. V. Articles of lishing efficacy to be a rigorous one; Congress 93 S.Ct. 2469, 412 U.S. 609, 37 L.Ed.2d 207. Drug HORMONIN, D.C.N.J.1980, 498 intended that clinical impressions of practicing If, on October 9, 1962, laetrile was marketed F.Supp. 424, affirmed 672 F.2d 902, 904. 1. Constitutionality physicians and poorly controlled experiments for exactly the same uses for which it is present- 3. With other laws would not constitute an adequate basis for es- ly being sold and was generally recognized by A single administrative proceeding in which Reach of scientific inquiry under subsec. (d) of tablishing efficacy. Weinberger V. Hynson, qualified experts as safe for those uses, it is each manufacturer of drug challenged on ground of efficacy may be heard is constitutionally per- this section defining general contours of "sub- Westcott and Dunning, Inc., Va.1978, 93 S.Ct. exempt, under grandfather clause contained in 2469, 412 U.S. 609, 37 L.Ed.2d 207. 1962 amendment to this chapter [set out as a missible measured by requirements of procedur- stantial evidence" respecting efficacy of drug for al due process. Weinberger V. Hynson, West- purposes of refusal or approval of a new drug Drug Price Competition and Patent Term note under section 321 of this title], from the cott and Dunning, Inc., Va.1973, 98 S.Ct. 2469, application, and under section 321 of this title Restoration Act has the general purposes of test of general recognition by experts as being 412 U.S. 609, 87 L.Ed.2d 207. increasing the availability of low-cost drugs by safe and effective for its claimed uses. Ruther- defining a "new drug," subject to provisions of Defendant could be indicted for violations of this chapter, as a drug not generally recognized expanding the generic drug approval procedure ford V. U.S., C.A.Okl.1976, 542 F.2d 1137, on among experts as effective as well as safe for its and of encouraging new drug research by re- remand 424 F.Supp. 105. recordkeeping regulations promulgated by Food intended uses, is precisely the same. Wein- storing some of the patent term lost while drug Where new drug application had been ap- and Drug Administration (FDA) for new drug berger V. Bentex Pharmaceuticals, Inc., S.C. products undergo testing and await FDA pre- proved and no proceedings had been commenced investigations, as FDA had authority to create 1973, 93 S.Ct. 2488, 412 U.S. 645, 37 L.Ed.2d market approval. Glaxo Operations UK Ltd. V. by the Secretary to withdraw approval, drug regulations and delegation of that authority to 235. Quigg, C.A.Fed. (Va.) 1990, 894 F.2d 392. FDA satisfied constitutional concerns of non- manufacturer's purported withdrawal prior to delegation doctrine. U.S. V. Garfinkel, C.A.8 Court would presume that Congress was This chapter and underlying regulations gov- day immediately preceding effective date of 1962 (Minn.) 1994, 29 F.3d 451. aware that this chapter would effect the earning erning approval of marketing of new drugs were effectiveness amendment [set out as a note un- potentiality of 8 drug patentee and chose to not intended to provide patent-like protection der section 321 of this title] to this chapter was This section requiring new drug approval does permit that effect when it tightened require- for a seller who has gained approval of a pioneer ineffective for purpose of determining whether not deny equal protection to person suffering ments for obtaining approval for new drugs. new drug application. Upjohn Mfg. Co. V. drugs qualified for permanent "grandfather from Down's Syndrome or their parents and Roche Products, Inc. V. Bolar Pharmaceutical Schweiker, C.A.Mich.1982, 681 F.2d 480. clause" exemption from enlarged definition of a custodians. Duncan V. U.S., D.C.Okl.1984, 590 Co., Inc., C.A.Fed.1984, 733 F.2d 858, certiorari Purpose of this section relating to new drugs "new drug" included in amendments. USV F.Supp. 39. denied 106 S.Ct. 183, 469 U.S. 856, 83 L.Ed.2d is to protect public against danger to human life Pharmaceutical Corp. V. Richardson, C.A.Va. This chapter's statutory scheme for gaining 117. arising from use of unsafe and ineffective drugs 1972, 461 F.2d 223, affirmed 93 S.Ct. 2498, 412 approval for new drug applications in order to Orders which do not deny or withdraw a new- by assuring that, before any drug is marketed, it U.S. 655, 37 L.Ed.2d 244. permit introduction into interstate commerce of drug application are reviewable under Adminis- will have been carefully reviewed by Food and Manufacturer, whose marketing approval for such new drug does not require Food and Drug trative Procedure Act, sections 551 et seq. and Drug Administration experts, and Congress' ex- its drug was outstanding and had not been Administration to approve or disapprove any 701 et seq. of Title 5, if they declare a "new clusion of generally recognized drug products legally withdrawn on date of 1962 amendment to new drug in absence of application and is consti- drug" status. North American Pharmacal, Inc. from definition of "new drug" is very narrow this chapter was not entitled to claimed benefit tutional as exercise of Congress's power to set V. Department of Health, Ed. and Welfare, one, which is not intended to permit pharmaceu- of section 107 of Pub.L. 87-781, set out as a note standards in order to protect public from unsafe C.A.8, 1973, 491 F.2d 546. tical manufacturer to substitute its opinion re- under section 321 of this title, applicable to drugs, even though drug application may involve Provision of section 321 of this title defining a garding safety or effectiveness of a drug for that drugs not covered by an effective marketing costs which are so substantial as to cause per- sons appropriately situated to forego compliance "new drug" as any drug not generally recog- of the Food and Drug Administration or to order on day immediately before enacting date nized among qualified experts as safe and effec- require court to develop its own body of scienti- of amendments. Hynson, Westcott & Dunning, with this chapter. Gadler V. U.S., D.C.Minn. 1977, 425 F.Supp. 244. tive for use under conditions prescribed, recom- fic knowledge in substitution for that of the Inc. V. Richardson, C.A.4, 1972, 461 F.2d 215, mended, or suggested in labeling thereof should FDA. Premo Pharmaceutical Laboratories, Inc. modified on other grounds 93 S.Ct. 2469, 412 V. U.S., C.A.N.Y.1980, 629 F.2d 795. 200 U.S. 609, 37 L.Ed.2d 207. 201 41 8 300 FOOD AND DRUGS Note 5a FOOD AND DRUGS 21 § 355 5a. Generally 6. Rules and regulations Note 6b While this chapter provides the Food and Strict and demanding standards in regulations In rejecting evidence submitted in support of counter drug market were unlawful to the ex- Drug Administration with sanctions, such as civil issued under this subchapter, which standards new drug application, Food and Drug Adminis- tent that they affirmatively sanctioned continued injunction proceedings, criminal penalties, and in bar anecdotal evidence indicating that doctors tration should make its criticisms express and marketing of Category III drugs in the absence rem seizure and condemnation, to enforce prohi- "believe" in efficacy of a drug, are amply justi- detailed and cite pertinent regulations and evi- of an administrative determination that the bition against sale in commerce of any article fied by legislative history of its provisions. dentiary flaws. Cooper Laboratories, Inc. V. products were generally recognized by experts without an effective new drug application, this Weinberger V. Hynson, Westcott and Dunning, Commissioners, Federal Food and Drug Admin- as safe and effective. Cutler V. Kennedy, chapter does not create a dual system, one Inc., Va.1973, 93 S.Ct. 2469, 412 U.S. 609, 37 istration, 1974, 501 F2d 772, 163 U.S.App.D.C. D.C.D.C.1979, 475 F.Supp. 888. administrative and the other judicial. CIBA L.Ed.2d 207. 212. While Food and Drug Administration is to be Corp. V. Weinberger, N.J.1978, 93 S.Ct. 2495, Food and Drug Administration (FDA) may Under regulation pursuant to this section, as given administrative flexibility to make regula- 412 U.S. 640, 87 L.Ed.2d 230. impose regulations on development of drugs but it existed prior to 1960 a drug company had the tions and determine new drug status of individu- Food and Drug Administration was not com- authorized regulations must be for purpose of option of filing a supplemental application for a al drugs or classes of drugs, argument that Food pelled to pursue new drug procedure in the proposed change in the conditions under which conditioning investigational drug exemptions and Drug Administration lacks administrative laetrile situation in the absence of an application. which will apply only to drugs intended for use such drug is to be used instead of a new drug resources to insurer compliance with this sec- Rutherford V. U.S., C.A.Okl.1976, 542 F.2d 1137, by qualified experts investigating the safety and application when a new drug application has tion, cannot be permitted to postpone to some on remand 424 F.Supp. 105. already been approved, thereby eliminating the effectiveness of the drug, but regulations may indefinite future date implementation of re- need to duplicate parts of the application previ- Where it was well-known that liver damage not require clinical investigators to submit inves- quired preclearance approval of new drug appli- ously approved, rather than mere option of filing was among adverse effects on humans from tigational reports directly to FDA. U.S. V. Gar- cations. Hoffmann-LaRoche, Inc. V. Wein- a supplemental application or not. Hoffman V. prolonged use of drug, drug manufacturer, finkel, C.A.8 (Minn.) 1994, 29 F.3d 451. berger, D.C.D.C.1975, 425 F.Supp. 890. Sterling Drug, Inc., C.A.Pa.1973, 485 F.2d 182, The Food and Drug Administration does not which was neither sponsor nor promoter of Amendment to Food and Drug Administra- on remand 874 F.Supp. 850. drug, was not liable for death of user from liver have unbridled discretion to do what it pleases tion's over-the-counter drug review regulations, Regulations whereby new drug application damage on theory that drug had not been prop- in determining whether product is a "new drug" creating 12-month period for comment on tem- would not be accepted for filing if incomplete on erly tested for dangerous and harmful side ef- since its procedures must satisfy the rudiments porary final monographs, which consumers al- its face by omission of required material and fects it would produce. Brick V. Barnes-Hines of fair play. National Ethical Pharmaceutical leged served only to delay implementation of which called for notice to the applicant and, in Pharmaceutical Co., Inc., D.C.D.C.1977, 428 Food, Drug, and Cosmetic Act's safety and effi- Ass'n V. Weinberger, D.C.S.C.1978, 865 F.Supp. later regulation, provided for requested filing F.Supp. 496. 785, affirmed 508 F.2d 1051. cacy requirements by further postporting publi- over protest were reasonable and valid. Duro- cation of final monographs, was consistent with vic V. Richardson, C.A.III.1978, 479 F.2d 242, 6a. Application, cancellation of 5b. Offenses within section Act, and was designed to facilitate gathering of certiorari denied 94 S.Ct. 232, 414 U.S. 944, 38 Where new drug application applicant fails to Cancer patient's purchase of Laetrile in Mexi- supplemental information to promote efficiency, L.Ed.2d 168, rehearing denied 94 S.Ct. 611, 414 produce adequate and well-controlled studies co and subsequent transportation of that drug to and thus was not arbitrary, capricious or other- U.S. 1088, 38 L.Ed.2d 494. showing efficacy, summary disposition of appli- Minnesota for his personal use constituted intro- wise improper. Cutler V. Hayes, 1987, 818 F.2d Food and Drug Administration's (FDA) regu- cation is authorized. Cooper Laboratories, Inc. duction of Laetrile into interstate commerce and 879, 260 U.S.App.D.C. 230. lation concerning waiver of in vivo bioequiva- V. Commissioner, Federal Food and Drug Ad- was prohibited by this section prohibiting intro- Authority granted by subsec. (i) of this section lence testing for approval of generic drugs in ministration, 1974, 501 F.2d 772, 163 U.S.App. duction or delivery for introduction into inter- allowing the Secretary of Health and Human certain circumstances did not exceed FDA's au- D.C. 212. state commerce any new drug, unless approval Services to establish "other conditions relating thority under Hatch-Waxman Amendments While an applicant for approval to market a of application by Food and Drug Administration to the protection of public health" with respect which govern FDA's approval of applications for new drug may withdraw his application during is effective with respect to such drug; this sec- to maintaining accurate drug records is insuffi- generic versions of pioneer drugs, where FDA pendency thereof, he has no such right after tion does not purport to apply only to manufac- cient legislative guidance for the issuance of regulation did not attempt to waive bioequiva- approval of the application by the Secretary; at turers or distributors, but plainly states that "no regulations which, if violated, would furnish the lence determinations but, rather, regulation per- that point only the Secretary can withdraw the person shall introduce or deliver for introduction basis for criminal liability. U.S. V. Smith, mitted waiver of discrete, specific form of in vivo approval USV Pharmaceutical Corp. V. Rich- into interstate commerce any new drug." Ga- C.A.Cal.1984, 740 F.2d 784. testing for those categories of drugs where in ardson, C.A.Va.1972, 461 F.2d 223, affirmed 93 dler V. U.S., D.C.Minn.1977, 425 F.Supp. 244. vivo bioavailability or bioequivalence of drug The fact-finding procedures employed by S.Ct. 2498, 412 U.S. 655, 87 L.Ed.2d 244. product could be considered self-evident based 5c. Authority of Secretary Food and Drug Administration in approving on other data Federal Food, Drug, and Cosmet- Criteria which were used by Secretary of British drug manufacturer's new drug applica- ic Act, § 505(j)(7)(B), as amended, 21 U.S.C.A. Health, Education, and Welfare in deciding to Although this section requiring Secretary of tion and rejecting American drug manufactur- $ 355(j)(7)(B). Fisons Corp. V. Shalala, D.D.C. suspend new drug applications for phenformin Health, Education and Welfare (now Secretary er's petition urging denial of the application was 1994, 860 F.Supp. 859. hydrochloride on ground that drug posed an of Health and Human Services] to disapprove a adequate, since Administration followed applica- "imminent hazard" did not improperly reflect new drug application if he or she finds that ble statutory and regulatory criteria for approv- It is not a crime for protocol investigators to intent of Congress nor were they at substantial proposed labeling is false or misleading reflects ing the application, and engaged in informal fail to maintain adequate and accurate records; Congress' continuing concern that drug labeling fact-finding procedures to gather evidence con- although statute expressly authorizes promul- variance with Food and Drug Administration regulation. Forsham V. Califano, D.C.D.C.1977, should be both truthful and complete, it cannot cerning the safety and effectiveness of the drug. gation of regulations requiring drug manufactur- Upjohn Mfg. Co. V. Schweiker, C.A.Mich.1982, ers or sponsors of clinical investigations to main- 442 F.Supp. 203. fairly be read to encompass authority for requir- ing the delivery of written material to patient at 681 F.2d 480. tain and submit reports setting forth the results Under this section authorizing Secretary of of clinical tests involving experimental drugs to Health, Education, and Welfare to suspend new time of dispensing and these provisions, as con- trasted with mislabeling provisions of this chap- Where drug manufacturer failed to comply Food and Drug Administration (FDA), statute's drug application for a drug which poses an ter, apply only at moment of shipment in inter- with this chapter and regulations governing the general regulatory authority is insufficient legis- "imminent hazard," meaning of "imminent haz- state commerce and not to action subsequent to manufacturing, sampling and labeling of pro- lative guidance for issuance of regulations which, ard" is not to be restricted to a concept of crisis. shipment in interstate commerce. Pharmaceuti- posed new drug, new drug application could not If violated, would furnish basis for criminal lia- Forsham V. Califano, D.C.D.C.1977, 442 F.Supp. cal Mfrs. Ass'n V. Food and Drug Administra- be approved. Edison Pharmaceutical Co., Inc. bility. U.S. V. Garfinkel, D.Minn.1993, 822 203. tion, D.C.Del.1980, 484 F.Supp. 1179. V. Food and Drug Admin., Dept. of Health, Ed. F.Supp. 1457. 6b. Exhaustion of remedies and Welfare, 1979, 600 F.2d 831, 195 U.S.App. In deciding that phenformin hydrochloride D.C. 17. Regulation promulgated by the Food and Failure of consumers of over-the-counter Drug Administration (FDA), which interpreted posed an imminent hazard, Secretary was autho- drugs to exhaust their administrative remedies Only those studies of effectiveness of drug "feasibility" exception to statutory prohibition rized to create within suspension order volun- before challenging Food and Drug Administra- that meet the standards particularized in 21 against administration of unapproved drugs to tary system of limited distribution to those small tion's regulations implementing Food, Drug and C.F.R. 130.14 pertaining to adequate and well- permit administration of such drugs in specific number of patients for whom it might be deter- Cosmetic Act program concerning new over-the- mined that drug's benefits outweighed its risks controlled studies are acceptable in determining combat circumstances, was not arbitrary, capri- counter drugs did not require dismissal of action whether there is substantial evidence to support cious, or manifestly contrary to statute. Doe V. and was also authorized to delay implementation in view of Food and Drug Administration's waiv- the claims of effectiveness for any drug. Ster- Sullivan, D.D.C.1991, 756 F.Supp. 12, affirmed of order for 90 days. Forsham V. Califano, er of issue by failing to raise objection and D.C.D.C.1977, 442 F.Supp. 203. ling Drug Inc. V. Weinberger, C.A.2, 1974, 503 938 F.2d 1370, 291 U.S.App.D.C. 111. futility of pursuing administrative remedies. F.2d 675. Regulations adopted by the Food and Drug Cutler V. Hayes, 1987, 818 F.2d 879, 260 202 Administration for policing the nation's over-the- U.S.App.D.C. 230. 21 § 355 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 Note 6b Note 7b When Food and Drug Administration has pri- 6c. Reapplication Options available to Food and Drug Adminis- drugs, and those exemptions must be condi- mary jurisdiction to determine status of product, one seeking to contest agency's determination Unless pharmaceutical manufacturer can show tration such as good manufacturing practice reg- tioned on imposition of informed-consent provi- that its drug product is generally recognized, ulations and section 351 of this title did not sions on manufacturers or sponsors. U.S. V. must exhaust all administrative remedies before seeking judicial review. Biotics Research Corp. among experts qualified by scientific training adequately protect the public so as to obviate Garfinkel, C.A.8 (Minn.) 1994, 29 F.3d 451. V. Heckler, C.A.Nev.1983, 710 F.2d 1875. and experience to evaluate safety and effective- need for preclearance, as "new drugs", generic As an exemption to a comprehensive regulato- ness of drugs, as safe and effective for use under drugs having the same active ingredients and in ry statute concerned with public safety, grandfa- Food and Drug Administration and California conditions prescribed and that, being 80 recog- some cases the same inactive ingredients as in ther clause of 1962 amendments to this subchap- State Department of Health Services had pri- nized, it has been used to material extent or for their FDA-approved pioneer counterparts. U.S. ter is to be strictly construed, and party seeking mary jurisdiction to determine whether persons material time under such conditions, manufac- V. Premo Pharmaceutical Laboratories, Inc., to grandfather in pre-1962 drug bears burden of could traffic in new drug; thus, if plaintiff turer must file with Food and Drug Administra- wished to obtain Laetrile to use in the nutrition- D.C.N.J.1981, 511 F.Supp. 958. proof as to each condition. U.S. V. Articles of tion a new drug application and establish by Drug Consisting of following: 5,906 Boxes, al program for prevention of cancer, he had to substantial evidence to satisfaction of Food and Food and Drug Administration's policy of per- C.A.Puerto Rico 1984, 745 F2d 105, certiorari exhaust his administrative remedies prior to Drug Administration that drug is safe and effec- mitting new drugs that were chemically equiva- denied 105 S.Ct. 1358, 470 U.S. 1004, 84 L.Ed.2d seeking judicial relief. Carnohan V. U.S., tive for its intended uses. Premo Pharmaceuti- lent to pioneer drug for which full new drug 379. C.A.Cal.1980, 616 F.2d 1120. cal Laboratories, Inc. V. U.S., C.A.N.Y.1980, 629 application was in effect to be marketed without F.2d 795. Grandfather clause exempting certain drugs Alleged statements by Food and Drug Admin- approved new drug application contravened from requirement under this chapter of provid- istration (FDA) employees that they intended to Food and Drug Administration acted reason- clear statutory requirement of preclearance, was ing effectiveness makes no distinction between waive bioequivalence testing for certain abbrevi- ably in interpreting term "drug" as used in not within intendment of 1962 amendments to pioneer and "me-too" drugs but exempts only ated new drug applications and that they intend- provisions of Federal Food, Drug and Cosmetic this section and legislative scheme they embody, that generic class of drugs which on October 9, ed to treat impurity analysis for generic drugs Act requiring information to be filed on "any and, by permitting marketing of large classes of 1962, were not covered by an effective new drug differently were not final agency actions and, patent which claims the drug for which the applicant submitted the application," to mean such drugs, violated its own regulations. Hoff- application. Smithkline Corp. V. Food and Drug therefore, could not be challenged under Admin- mann-La Roche, Inc. V. Weinberger, D.C.D.C. Administration, 1978, 587 F.2d 1107, 190 istrative Procedure Act. Fisons Corp. V. Shala- "drug product" for which new drug application 1975, 425 F.Supp. 890. U.S.App.D.C. 210. la, D.D.C.1994, 860 F.Supp. 859. was filed. Pfizer, Inc. V. Food and Drug Ad- min, D.Md.1990, 758 F.Supp. 171. Where there was similarity in formula be- Manufacturer of drug called "PAX," which Soap manufacturer was required to exhaust tween drug marketer's citrus bioflavonoid drugs his administrative remedies with Food and Drug 7. Necessity of approval was a "new drug" within the meaning of this subject to new drug applications and its "me- Administration regarding to determination of section, would be preliminarily enjoined from Durovic V. Richardson, 327 F.Supp. 386, [main too" drugs, both the NDA'd and the "me-too" whether soap was "safe and effective" for partic- volume] affirmed 479 F.2d 242, certiorari denied introducing and delivering such drug into inter- drugs would be treated alike and neither could ular purpose for which it had already been 94 S.Ct. 232, 414 U.S. 944, 38 L.Ed.2d 168, state commerce from foreign trade zone unless qualify for exemption under the "grandfather marketed, and whether it was therefore not rehearing denied 94 S.Ct. 611, 414 U.S. 1088, 88 and until approval of an application filed pursu- clause" from 1962 effectiveness amendment [set subject to new drug hearings. Farquhar V. L.Ed.2d 494. ant to this section was effective with respect to out as a note under section 321 of this title] to Food and Drug Admin., D.C.D.C.1985, 616 Drug that had same active ingredient as Food such drug. U.S. V. Yaron Laboratories, Inc., this chapter. USV Pharmaceutical Corp. V. F.Supp. 190. D.C.Cal.1972, 865 F.Supp. 917. Richardson, C.A.Va.1972, 461 F.2d 223, affirmed and Drug Administration-approved drug prod- 93 S.Ct. 2498, 412 U.S. 655, 37 L.Ed.2d 244. Drug manufacturer which marketed drug un- uct, which had been marketed for many years, der trademark and which filed pioneer new drug but which had different inactive ingredients, 7a. Exemptions In light of health risks associated with estro- application for that drug could maintain action could not be marketed without obtaining approv- Phrase "any drug," in "grandfather clause" of genic drug products, drug product which was challenging Food and Drug Administration's ap- al of new drug application from Food and Drug fixed combination of three unconjugated estro- Drug Amendments of 1962, set out as a note proval of new drug application to British manu- Administration, where it was not generally rec- gens was not apt subject for exemption from ognized among qualified experts as safe and under section 321 of this title, which exempts facturer and distributor of drug called "ibupro- requirement that expert consensus as to general effective for use under conditions stated in label- from effectiveness requirements any drug which fen," even though manufacturer had not ex- recognition of the product's safety and effective- hausted its administrative remedies where, to ing, there was no published scientific literature on date preceding enactment was commercially ness be founded upon substantial evidence in obtain withdrawal of British manufacturer's ap- as to drug to enable qualified experts to make used or sold in the United States, was not a order for the product to transcend "new drug" plication, manufacturer would have to show that necessary determination, experts had sharp dif- "new drug" as defined in this chapter as origi- status. U.S. V. Articles of Drug HORMO- drug was not safe or not effective and that ferences of opinion, both as to methods used and nally enacted, and was not covered by an effec- NIN, D.C.N.J.1980, 498 F.Supp. 424, affirmed avenue would have been fruitless. Upjohn Mfg. results claimed, and, although manufacturer had tive application for a new drug under this chap- 672 F.2d 902, 904. Co. V. Schweiker, D.C.Mich.1981, 520 F.Supp. sold 16,500,000 tablets there was no evidence ter as originally enacted, is used in the generic Practice of pharmacy exemption from sanc- 58, affirmed 681 F.2d 480. that drug had been used to material extent or sense, 80 that "me-toos," those drugs similar or tions of this chapter was not applicable where for any substantial period of time. Premo Phar- Where substantive questions as refined in identical to drugs with effective new drug appli- corporation disseminated information to solicit maceutical Laboratories, Inc. V. U.S., C.A.N.Y. cations, whether products of same or different applications for membership in its organization proceedings required decision as to whether 1980, 629 F.2d 795. Finkel memorandum to effect that Food and manufacturers "covered" by an effective new and, as a result of such memberships, prescrip- Drug Administration would approve post-1962 Constitutional rights of privacy and personal drug application, are not exempt from efficacy tions for its products were referred to single liberty do not give individuals the right to obtain requirements. USV Pharmaceutical Corp. V. pharmacy that specialized in compounding the duplicate new drug applications in reliance on published reports without fresh clinical investi- Laetrile free of lawful exercise of government Weinberger, Va.1973, 93 S.Ct. 2498, 412 U.S. drug. U.S. V. Sene X Eleemosynary Corp., Inc., gations or available raw data should be issued as police power. Carnohan V. U.S., C.A.Cal.1980, 640, 37 L.Ed.2d 230. D.C.Fla.1979, 479 F.Supp. 970. 616 F.2d 1120. a rule or as a general statement of policy, ex- Where there had been no completed tests or Regional compounding centers which per- Exemption under the "grandfather clause" of empt from notice and comment requirement, investigations to determine either the efficacy or questions should have been confronted squarely formed same function that doctors would other- the Drug Amendments of 1962, set out as a note safety of animal drugs, they were never general- and decided by the Food and Drug Administra- wise have performed by taking chemotherapeu- under section 321 of this title, is afforded only ly recognized as safe and effective for the uses tion before judicial review was sought and, thus, tic drugs approved by the FDA and diluting and for drugs that never had been subject to new intended, and thus "grandfather clause" exemp- case would be dismissed for failure to exhaust repackaging them into single-dosage units ready drug regulation. Weinberger V. Hynson, West- tion from the effectiveness requirement of this administrative remedies. Hoffmann-La Roche, to be used by patients did not fall within the cott and Dunning, Inc., Va.1973, 93 S.Ct. 2469, section was not applicable. U.S. V. 14 Cases Inc. V. Harris, D.C.D.C.1979, 484 F.Supp. 58. "repackaging" or "bioequivalent product" excep- 412 U.S. 609, 37 L.Ed.2d 207. More or Less, "Naremco Medi-Matic Free tions to federal premarketing approval require- Choice Poultry Formula", D.C.Mo.1974, 374 District court's assertion of jurisdiction over ments. U.S. V. Baxter Healthcare Corp., Food and Drug Administration (FDA) is re- F.Supp. 922. action for determination as to whether drug was N.D.Ill.1989, 712 F.Supp. 1352. quired to promulgate regulations allowing for a "new drug" would be premature prior to refus- New drug approval requirement applies to exemptions from operation of new drug applica- 7b. Defenses al of Food and Drug Administration to issue patients or users of a new drug as well as to tion process which will apply only to drugs Producer and distributor of nutritional, per- declaratory order Carolina Brown, Inc. V. Wein- berger, D.C.S.C.1973, 365 F.Supp. 310. manufacturers of it. Duncan V. U.S., D.C.Okl. intended solely for investigational use, by ex- sonal care and related products, and its officers 1984, 590 F.Supp. 39. perts to investigate safety and effectiveness of and employees, all of whom were prosecuted for 204 205 21 8 355 FOOD AND DRUGS Note 7b FOOD AND DRUGS 21 § 355 allegedly "misbranding" drug could not complain Va.1973, 93 S.Ct. 2498, 412 U.S. 640, 37 L.Ed.2d Note 9 that drug was improperly classified as prescrip- 230. therefore, for the Government to perform bioa- tion drug where they did not avail themselves of 944, 38 L.Ed.2d 168, rehearing denied 94 S.Ct. Parties cannot confer jurisdiction to deter- vailability, bioequivalence, and other qualified procedures to make its arguments before appro- 611, 414 U.S. 1088, 38 L.Ed.2d 494. mine "new drug" status of a drug; only Con- controlled tests to establish safety and efficacy. priate agency and waited until they had been Where drug was offered for use in the man- prosecuted to make arguments in district court. gress can do 80. Weinberger V. Bentex Phar- U.S. V. Articles of Drug, C.A.Pa.1978, 585 F.2d 575. agement of malignant tumors, "grandfather U.S. V. General Nutrition, Inc., W.D.N.Y.1986, maceuticals, Inc., S.C.1973, 93 S.Ct. 2488, 412 clause" in the Drug Amendments of 1962, set U.S. 645, 37 L.Ed.2d 235. 638 F.Supp. 556. Acceptance by the Federal Trade Commission out as note under section 321 of this title, had no Whether a particular drug is a "new drug," 80 of the Food and Drug Administration determi- Cancer patient's right to privacy would not effect on it, in determining whether a new drug as to require an effective new drug application nation that drug used by weight reducing clinic application was required. Durovic V. Richard- protect his importation for personal use of new before it may be introduced into commerce, was a new drug when used for the treatment of son, C.A.III.1973, 479 F.2d 242, certiorari denied drug Laetrile in violation of this section prohibit- ing introduction into interstate commerce of any depends in part on expert knowledge and expe- obesity, and thus that the fact should be dis- 94 S.Ct. 232, 414 U.S. 944, 38 L.Ed.2d 168, rience of scientists based on controlled clinical closed to consumers, was supported by substan- rehearing denied 94 S.Ct. 611, 414 U.S. 1088, 38 new drug unless approval of application by Food experimentation and backed by substantial sup- tial evidence and was reasonable. Simeon Man- L.Ed.2d 494. and Drug Administration is effective with re- port in scientific literature. Weinberger V. Ben- agement Corp. V. F.T.C., C.A.9, 1978, 579 F.2d spect to such drug. Gadler V. U.S., D.C.Minn. Drug is a "new drug," and thus is subject to tex Pharmaceuticals, Inc., S.C.1973, 93 S.Ct. 1137. 1977, 425 F.Supp. 244. seizure if shipped in interstate commerce with- 2488, 412 U.S. 645, 37 L.Ed.2d 235. Although substantial evidence of effectiveness out prior approval of a new drug application, 8. Interstate commerce Issue whether drugs were generally recog- for the labeled use is required for a drug to be unless it is presently regarded by qualified ex- In order for a court properly to condemn a nized as safe and effective and thus not "new generally recognized as effective, such substan- perts as both safe and effective for its intended drug item, a nexus must be shown between drug drugs" within this chapter and whether the tial evidence may exist long before the drug is use or unless it was generally regarded by quali- item and commerce 80 as to invoke federal drugs were exempt from new effectiveness re- generally recognized as effective for that use; fied experts on the October 9, 1962, effective jurisdiction; on the one hand, in a case in which quirements by reason of grandfather clause in approval of a new drug application does not, date of the "grandfather clause" exemption as a drug is found to be misbranded, it may be the Drug Amendments of 1962, set out as a note alone, remove the approved drug from new drug safe for intended use. U.S. V. An Article of condemned when introduced into or while in under section 321 of this title, were kinds of status. Simeon Management Corp. V. F.T.C., Drug "Bentex Ulcerine", C.A.Tex.1972, interstate commerce or while held for sale after issues peculiarly suited to initial determination C.A.9, 1978, 579 F.2d 1187. 469 F.2d 875, certiorari denied 93 S.Ct. 2772, shipment in interstate commerce; on the other by the Food and Drug Administration with its In the absence of evidence as to how laetrile 412 U.S. 938, 37 L.Ed.2d 397. hand, if a drug is confiscated because it is an specialized competence and expertise, and dis- was marketed before passage of 1962 amend- Fact that pre-1962 new drug application drugs trict court's referral of these issues to the Ad- unapproved "new drug," it must be shown to ministration was appropriate. Weinberger V. ment to this chapter requiring drugs to be rec- became generally recognized as safe on or be- have been introduced or delivered for introduc- Bentex Pharmaceuticals, Inc, S.C.1978, 93 S.Ct. ognized as effective, court could not determine fore effective date of 1962 effectiveness amend- tion in interstate commerce before it may be whether drug was subject to the new require- ments [set out as a note under section 321 of 2488, 412 U.S. 645, 37 L.Ed.2d 235. condemned. U.S. V. Articles of Drug, C.A.Pa. ment or was grandfathered in. Rutherford V. this title] to this chapter did not establish that 1978, 585 F.2d 575. Food and Drug Administration has jurisdic- U.S., C.A.Okl.1976, 542 F.2d 1137, on remand such drugs were no longer covered by an effec- tion to determine jurisdictional question whether A drug is "in interstate commerce" for pur- 424 F.Supp. 105. tive new drug application and, thus, exempt, a particular drug is a "new drug" 80 as to acquire an effective new drug application before "New drug" for purposes of this section is a under the permanent "grandfather clause", from poses of this section, if one of its components previously traveled in interstate commerce, and drug may be introduced into commerce. Wein- substance which is generally recognized by sci- the amendment. USV Pharmaceutical Corp. V. entific experts as safe and effective for use Richardson, C.A.Va.1972, 461 F.2d 223, affirmed if finished drug itself is destined in ordinary berger V. Hynson, Westcott and Dunning, Inc., 93 S.Ct. 2498, 412 U.S. 655, 37 L.Ed.2d 244. course of business for interstate distribution; Va.1973, 93 S.Ct. 2469, 412 U.S. 609, 87 L.Ed.2d under the conditions prescribed or suggested in therefore, since ingredients of drugs seized from 207. the labeling thereof unless, prior to 1962, it was Hair care products which were intended to pharmaceutical laboratory traveled in interstate subject to the requirements of the Food and prevent or cure baldness or thinning hair and commerce, were manufactured in usual course of Toothpaste manufacturer failed to show by laboratory's business, and were intended for in- substantial evidence that potassium nitrate Drugs Act of 1906, Act June 30, 1906, Ch. 3915, which had not been generally recognized as safe 34 Stat. 768. Rutherford V. U.S., C.A.Okl.1976, and effective for their intended use were "new terstate distribution, there was sufficient nexus made contribution to claimed effect of treating 542 F.2d 1137, on remand 424 F.Supp. 105. drugs" and, as such, were subject to regulation with interstate commerce to justify their seizure. dentin hypersensitivity and could not rely solely by Food and Drug Administration (FDA). U.S. U.S. V. Articles of Drug upon laboratory testing profiles for toothpastes Fact that label contained a contraindication of V. Kasz Enterprises, Inc., D.R.I.1994, 855 WANS, D.C. with single active ingredient of sodium MFP to use in cases of "known or suspected malignan- Puerto Rico 1981, 526 F.Supp. 703. F.Supp. 534. prove anticaries effectiveness; therefore, tooth- cies" did not preclude consideration of danger of Within subsec. (a) of this section, "into inter- activation of latent cancer of prostate in deter- Before a product can be exempted from statu- paste combining sodium MFP and potassium state commerce" necessarily encompasses intro- nitrate was "new drug" for which application mining whether drug marketed by claimant was tory new drug preclearance procedures it must duction of items into flow of shipments and a new drug within this subchapter especially in be generally recognized by qualified experts as had to be filed and approved before marketing. transportation within United States, even if the U.S. V. Articles of Drug, C.A.7 (III.) 1987, 826 light of evidence that in four out of five cases a safe and effective for its intended use, and "gen- final destination of the drug is not within the F.2d 564. patient may have latent cancer of the prostate eral recognition" requirement does not involve United States. U.S. V. An Article of Drug Con- though not known or suspected. U.S. V. actual safety or effectiveness of product, rather sisting of 197 Boxes, More or Less, each Con- Food and Drug Administration memorandum, 1,048,000 Capsules, More or Less, "Afrodex," it is product's reputation in scientific community concerning approval of new drug applications for 467. taining 150 Capsules, D.C.Tex.1981, 520 F.Supp. generic versions of drugs first marketed after C.A.Tex.1974, 494 F.2d 1158. that is relevant. U.S. V. 225 Cartons, More or Less, of an Article of Drug, D.N.J.1988, 687 1962 that are based on reports in the scientific The newness of a drug within meaning of F.Supp. 946. 9. New drug, determination of status as literature to establish the drug's safety and ef- provision of this section relating to introduction fectiveness, was consistent with published regu- into interstate commerce of any "new drug" may Drug manufacturer's application for approval Although drug marketer in 1961 had stated in arise by reason of a new or different recom- of oral dosage of injectable calcium product, lations of the Administration; the memo did not a letter to director of new drug branch of bureau of medicine in the Food and Drug Administra- conflict with regulation requiring an applicant to mended use for the drug even though the same even if properly termed "paper" new drug appli- submit reports of all clinical tests sponsored or drug may not be a "new drug" when used for cation or abbreviated new drug application, was tion that a certain class of products were no not subject to competing manufacturer's exclu- received by the applicant, nor did it conflict with another disease. Hoffman V. Sterling Drug, longer considered to be new drugs, and market- Inc., C.A.Pa.1973, 485 F.2d 132, on remand 374 sivity rights where former's application did not regulation stating that certain summaries of er in 1961 had stopped filing supplemental infor- safety and effectiveness data do not constitute F.Supp. 850. refer to latter's oral product or to any investiga- mation as required by regulation with regard to tions which were conducted by or for the latter; full reports of investigations. Burroughs Well- products for which new drug applications had Affidavits in declaratory judgment action es- hence, effective date of approval of former's come Co. V. Schweiker, C.A.N.C.1981, 649 F.2d become effective, marketer's new drug applica- tablished that drug intended for use in manage- application was not delayed by 1984 amend- 221. tions had not been withdrawn prior to 1962 80 ment of malignant tumors had not, either before ments to Federal Food, Drug, and Cosmetic Act. that its products were no longer covered by an Requirements of "new drug" section of this or after the Drug Amendments of 1962, set out Burroughs Wellcome Co. V. Bowen, E.D.N.C. effective application for purposes of "grandfa- chapter, namely, general safety and effective- as note under section 321 of this title, achieved 1986, 630 F.Supp. 787. ther clause" in Drug Amendments of 1962, set ness recognition, were met once the Government general recognition among qualified experts as Government can prove lack of "general recog- out as a note under section 321 of this title. admitted that all of manufacturer's drugs were safe and effective for such use, 80 as to be nition" of drug as safe and effective for recom- USV Pharmaceutical Corp. V. Weinberger, the same generically as a drug already approved exempt from requirement of new drug applica- mended uses SQ as to require filing of new drug as safe and effective and it was not necessary, tion. Durovic V. Richardson, C.A.III.1973, 479 application by proving absence of material fact 206 F.2d 242, certiorari denied 94 S.Ct. 232, 414 U.S. as to any of following issues: general recogni- 21 § 355 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 Note 9 Note 12 tion in fact among nation's experts that seized fair grounds for litigation. Rizzo V. U.S., Bristol-Myers Co. V. F.T.C., C.A.2, 1984, 738 exclusivity depending primarily on pharmaceuti- drugs are safe and effective for intended use, D.C.N.Y.1977, 432 Supp. 356. F.2d 554, certiorari denied 105 S.Ct. 960, 469 cal novelty, the phrase "active ingredient (in- existence of adequate and well-controlled studies Food and Drug Administration does not have U.S. 1189, 83 L.Ed.2d 966. cluding any ester or salt of the active ingredi- which constitute substantial evidence of safety unbridled discretion to do what it pleases in Before two or more drugs may be recombined ent)" was ambiguous, as the phrase could refer and effectiveness required for approval of new determining whether a product is a new drug, in single product, manufacturer must demon- to either the active ingredient of the original drug application, and generally available scienti- and its procedures must satisfy rudiments of fair strate by adequate and well-controlled investiga- approved drug or to the active ingredient in the fic literature substantiating expert consensus of play. Rutherford V. U.S., D.C.Okl.1977, 429 tions that each additional component provides new drug. Abbott Laboratories V. Young, 1990, safety and effectiveness. U.S. V. Articles of F.Supp. 506. specific benefit to patient that warrants in- 920 F.2d 984, 287 U.S.App.D.C. 190, certiorari Drug, N.D.IIL1985, 624 F.Supp. 776, affirmed 826 F2d 564. Where shelf life of drug had been exceeded creased risk. U.S. V. 225 Cartons, More or denied 112 S.Ct. 76, 116 L.Ed.2d 49. and, beyond the Food and Drug Administration Less, of an Article of Drug, D.N.J.1988, 687 Food and Drug Administration Compliance F.Supp. 946. 12. Submission of investigative reports approved shelf life, it was a drug of unknown Policy Guide did not bar enforcement action effectiveness, it was, in effect, a "new drug" With respect to combination drug, it must be Claimant failed to demonstrate that the Food against manufacturer of toothpaste grounded on without Administration approval and had to be demonstrated that the combination of ingredi- and Drug Administration committed a clear er- its introduction into interstate commerce with- presumed dangerous. Blanton V. U.S., D.C.D.C. ents is generally recognized as safe and effective ror of judgment or acted arbitrarily and capri- out approved new drug application where lan- 1977, 428 F.Supp. 860. in order for the drug to transcend "new drug" ciously in denying claimant's request for relabel- guage of Guide at issue was not statement of Food and Drug Administration has complete status. U.S. V. Articles of Drug HORMO- ing of medical device known as "Diapulse" de- policy or interpretation constituting advisory authority to determine which drugs are "new" NIN, D.C.N.J.1980, 498 F.Supp. 424, affirmed vice, in light of the FDA's thorough examination opinion and where Guide discussed action to be and require an approved new drug application in 672 F.2d 902, 904. of claimant's supporting documents and charac- taken by Food and Drug Administration person- order to be sold to the public. U.S. V. Marcen Although each of the components of a drug terization of studies as either concerning basic nel only and did not purport to address behavior Laboratories, Inc., D.C.N.Y.1976, 416 F.Supp. may be generally recognized as safe and effec- biological phenomena which offered little more by anyone outside Administration. U.S. V. Arti- 453, affirmed 556 '2d 562. tive, a new drug is created when they are com- than encouragement for follow-up studies, stud- cles of Drug Promise Toothpaste for Sensi- designed for use for performing in home, bined together in a new and different formula- ies with animals which were only indicative as to tive Teeth, D.C.III.1984, 594 F.Supp. 211. "preliminary screening test" by which human tion. U.S. V. An Article of Drug Labeled "En- efficacy of device, studies in humans concerning Generic drugs manufactured without submis- trol-C Medicated," D.C.Cal.1973, 362 F.Supp. medical conditions differing from those proposed female may obtain indication of probability that sion to and approval by Food and Drug Admin- she is or is not pregnant was not "drug" within 424, affirmed 513 F.2d 1127. by claimant, and studies conducted with devices istration of a new-drug application or abbreviat- meaning of this section requiring that "new substantially different from "Diapulse." U.S. V. ed new-drug application were "new drugs" for 9b. Exclusive marketing period An Article of Device drug" may be marketed in interstate commerce Diapulse, C.A.7 (III) purpose of application requirement where al- without first filing "new drug application." U.S. A new drug developer's interpretation of the 1985, 768 F.2d 826. though active ingredients and in some cases V. Article of Drug-OVA II, D.C.N.J.1975, 414 phrase "active ingredient (including any ester or For purpose of determining whether a new inactive ingredients as well were the same as F.Supp. 660, affirmed, 585 F.2d 1248. salt of the active ingredient)" as permitting a drug is effective, substantial evidence consisting those in FDA-approved, pioneer counterparts The actual safety or efficacy of a drug is drug company to obtain an extended period of of well-controlled scientific testing is required there was expert testimony that such drugs irrelevant as to whether its safety and efficacy is market exclusivity for the new drug by applying and isolated case reports, random experience were not generally recognized among qualified generally recognized among qualified experts, for an approval of the acid first, followed by the and reports lacking details needed to permit experts as safe and effective and even assuming and an announcement by the Food and Drug salt, but not under the reverse sequence, was scientific evaluation are not to be considered. identity of ingredients quantitatively and quali- Administration or any other person as to the not a reasonable interpretation of the statute Edison Pharmaceutical Co., Inc. V. Food and tatively, there were potentially significant differ- actual effectiveness of a drug is not determina- giving developers of new drugs a specified peri- Drug Admin., Dept. of Health, Ed. and Welfare, ences in manufacturing processes between the tive, and is irrelevant, to the ultimate issue of od of market exclusivity. Abbott Laboratories 1979, 600 F.2d 831, 195 U.S.App.D.C. 17. generic and pioneer products. U.S. V. Premo whether a drug is a "new drug." National V. Young, 1990, 920 F.2d 984, 287 U.S.App.D.C. 190, certiorari denied 112 S.Ct. 76, 116 L.Ed.2d Substantial evidence supported finding of the Pharmaceutical Laboratories, Inc., D.C.N.J. Ethical Pharmaceutical Ass'n V. Weinberger, 1981, 511 F.Supp. 958. D.C.S.C.1973, 365 F.Supp. 735, affirmed 503 49. Commissioner, made in connection with refusal to approve new drug application, that studies Pharmaceutical manufacturer is not permitted F.2d 1051. Generic manufacturer of drug products con- submitted by drug manufacturer to prove the to substitute its judgment as to whether drug In determining whether a drug is "new drug" taining controlled released propranolol IIC1, efficacy of new drug were replete with inaccura- product is "new drug" for that of Food and Drug there must be determination of whether drug which had filed abbreviated new drug applica- cies and ambiguities and lacked protocol and Administration, nor is the court required to has mustered the requisite scientifically reliable tion, was entitled to 180 days of exclusivity from statistical analysis and that, therefore, the stud- develop its own body of scientific knowledge in evidence of safety and effectiveness before they date of first commercial marketing of manufac- ies were not "adequate and well controlled" substitution for the Administration. U.S. V. Ar- are in position to drop out of active regulation turer's product, even though relevant patent within the meaning of this section and did not ticles of Drug HORMONIN, D.C.N.J. by ceasing to be "new drug." National Ethical holder chose not to sue manufacturer for patent establish the efficacy of the new drug. Edison 1980, 498 F.Supp. 424, affirmed 672 F.2d 902, Pharmaceutical Ass'n V. Weinberger, D.C.S.C. infringement. Inwood Laboratories, Inc. V. Pharmaceutical Co., Inc. V. Food and Drug Ad- 904. 1973, 365 F.Supp. 735, affirmed 503 F.2d 1051. Young, D.D.C.1989, 723 F.Supp. 1523. min., Dept. of Health, Ed. and Welfare, 1979, Decision as to whether drug X-Otag Plus Where drug which consisted of 14 mgs. of Federal Food, Drug, and Cosmetic Act, 600 F.2d 831, 195 U.S.App.D.C. 17. shipped by defendants in interstate commerce chemical ingredient 9-aminoacridine hydrochlo- $ 505(j)(4)(D)(ii), as amended, 21 U.S.C.A. Studies conducted on manufacturer's old for- was a "new drug" and subject to requisite ap- ride and binder of 14 mgs. of polyvinylpyrroli- § 355(j)(4)(D)(ii), establishing five-year exclusive mulation of Fiorinal with Codeine were not well- proval before being held for sale in interstate done and which was marketed as prescription marketing period following approval of new drug controlled clinical investigations of products us- market was to be made by Food and Drug drug for alleviation of various vaginal infections application for nonantibiotic drug in which no ing manufacturer's new formulation in which Administration, as agency entrusted by Con- had much larger dosage than used in other abbreviated new drug application may be filed to gress with necessary expertise to make well- aminoacridine medication for vaginal infections, market generic version of such drug did not phenacetin was replaced with increased dosages of aspirin, and thus extrapolation of data derived informed decisions on issue, and was not a deci- was in tampon form rather than gel tablet and apply to provide manufacturer of new antibiotic from studies of old formulation could not be sion which was within jurisdiction of district cream form, and had binder, drug was "new drug with exclusive marketing period during drug" and not exempt from seizure based on used to obviate need for new drug application court in enforcement and injunction proceedings which Food and Drug Administration could not for new formulation; manufacturer did not sub- brought against defendants by United States. claim of misbranding. U.S. V. Article of Drug approve competitor's generic version of pioneer U.S. V. X-Otag Plus Tablets, D.C.Colo.1977, 441 "Mykocert", D.C.IIL.1972, 845 F.Supp. 571. antibiotic drug, particularly where Congress had mit any data to indicate bioequivalence of new formulation with old formulation. U.S. V. 225 F.Supp. 105, affirmed in part, remanded in part 9a. Components refused to amend language of provision pertain- Cartons, More or Less, of an Article of Drug, on other grounds 602 F.2d 1387. ing to approval of antibiotic drugs [Federal Federal Trade Commission order purporting Food, Drug, and Cosmetic Act, § 507, as amend- D.N.J.1988, 687 F.Supp. 946. Plaintiff who was dying from cancer of the to remedy wrongs which Commission has found ed, 21 U.S.C.A. § 357] to create similar exclusiv- In determining validity of approval of dupli- pancreas and who sought to enjoin the Food and not to have been committed should be set aside, ity period. Glaxo, Inc. V. Heckler, D.C.N.C. cate new drug application, law does not require Drug Administration from preventing importa- but portion of its order applying to "unusual or 1985, 623 F.Supp. 69. any single study, viewed in isolation, to provide tion or interstate transportation of Laetrile for special ingredient representations" for all of total support for Food and Drug Administra- purposes of his own consumption raised statuto- plaintiffs over-the-counter drugs was reasonably 9c. Active ingredient tion's action, but rather, record must be viewed ry questions as to classification of Laetrile as a related to violation made by misrepresenting In the context of a statute that gave develop- as whole, taking into account cumulative and "new drug" sufficiently serious to make them that plaintiffs analgesics did not contain aspirin. ers of new drugs a specified period of market reinforcing nature of evidence. Upjohn Mfg. 208 209 21 § 355 FOOD AND DRUGS Note 12 FOOD AND DRUGS 21 § 355 Co. v. Schweiker, D.C.Mich.1981, 520 F.Supp. Note 14 Regulation promulgated by Food and Drug 58, affirmed 681 F.2d 480. Administration with respect to "new drugs" indi- fects of drug. George V. Parke-Davis, 1987, 738 Trial court's order that drug manufacturer In determining whether allegedly misbranded cates that newness is a function of the novelty of P.2d 507, 107 Wash.2d 584. provide drug free of charge to participants in drug came under grandfather clause exemption a particular formulation, including the novel double-blind study of drug for 12 months after 13a. Clinical studies from requirement of "effectiveness," court could composition, combination, dosage, or administra- study was completed as agreed to in contract did properly consider reprints of professional medi- tion and, though regulation extends 80 far as to Food and Drug Administration bulletin, which not violate doctrine of primary jurisdiction by cal studies of the drug published by doctors in encompass new uses for a drug or new methods provided that physician may, as part of practice taking decision away from Food and Drug Ad- medical journals, and "dear doctor" letters of application, it does not encompass a scope 80 of medicine, prescribe different dosage for pa- ministration (FDA) with respect effectiveness of printed by claimant which were distributed to broad as to require bioavailability and bioequiva- tient without obtaining approval of the FDA, drug; FDA's determination of efficacy did not physicians in promoting the sale of the drug. lence tests once a drug is established as being related to drugs which already had received have to precede injunction requiring one year of U.S. V. 1,048,000 Capsules, More or Less, "Afro- the same generically as a drug already approved FDA approval, and did not support contention of drug be provided free of charge to participants dex", D.C.Tex.1972, 847 F.Supp. 768, affirmed safe and effective. U.S. V. Articles of Drug, claimant, who sought relabeling of medical de- who subjected themselves to double-blind study. 494 F.2d 1158. C.A.Pa.1978, 585 F.2d 575. vice known as "Diapulse" device, that differing Dahl V. HEM Pharmaceuticals Corp., C.A.9 Even if reliance on a single well-known active conditions of use between studies and relabeling (Nev.) 1993, 7 F.3d 1899. 13. Testing of drugs Commissioner of Food and Drug Administra- ingredient like gentian violet lowered test for proposal were irrelevant, in light of statutory Determination that new drug application was tion did not err in requiring drug manufacturers general recognition of efficacy and safety, ani- criteria contained in Federal Food, Drug, and "approved" in December of 1981 when manufac- mal drugs and food additive, which government Cosmetic Act, [§§ 505(d), 513(a)(3)(B)(i, ii)] as turer was informed of approval, even though the to show that their oral proteolytic enzymes were amended, 21 U.S.C.A. $$ 355(d), 360c(a)(3)(B)(i, therapeutically effective in order to satisfy re- sought to condemn, could not be properly approval was granted with the understanding quirement for FDA approval that drugs be ef- deemed to be generally recognized as safe or ii)], which provides that scientific studies must that remaining issues concerning final printed effective, in absence of any adequate, well con- be such that it could fairly and responsibly be labeling be resolved, was not arbitrary and ca- fective by showing of clinical, rather than merely statistical, significance. Warner-Lambert Co. V. trolled, completed test of safety or efficacy of concluded that drug or device will have effect it pricious, 80 that drug was not entitled to period these combinations. U.S. V. Articles of Food purports or is represented to have under condi- of nonpatent exclusivity under the Hatch-Wax- Heckler, C.A.8, 1986, 787 F.2d 147. and Drug Consisting of Coli-Trol 80, F4C-60 tions of use prescribed, recommended or sug- man Amendments. Mead Johnson Pharmaceu- Dismissal without prejudice of post-office pro- Feed Grade, Entrol-S Medicated, Entrol-P, gested in labeling or proposed labeling thereof. tical Group, Mead Johnson & Co. V. Bowen, ceeding against manufacturer of hair and scalp C.A.Ga.1975, 518 F.2d 743. U.S. V. An Article of Device Diapulse, C.A.7 1988, 838 F.2d 1332, 267 U.S.App.D.C. 882. products did not collaterally estop Food and (III.) 1985, 768 F2d 826. Drug Administration from denying efficacy of That pain is difficult, or even impossible, to Position of Food and Drug Administration that it could approve new drug application prior the treatment, since issue in post-office case measure quantitatively does not entail infessibil- Food and Drug Administration had estab- lished that published clinical studies on Florinal to submission of final labeling was reasonable concerned accuracy of advertising while issue ity of controlled tests for determining drug's efficacy 80 as to establish grounds for waiver of with Codeine Nos. 1 and 2 did not establish interpretation of statute where statute only re- before Food and Drug Administration was requisite recognition of product or contribution quired submission of proposed labeling and FDA whether data submitted constituted adequate regulations requiring efficacy of drug to be es- tablished by controlled investigation. Cooper of its components 80 as to obviate need for new regulation stated that approval would ordinarily and well-controlled studies, and since dismissals Laboratories, Inc. V. Commissioner, Federal drug application with respect to drugs; manu- follow submission of final labeling. Norwich without prejudice do not constitute a final deter- facturer submitted no studies with respect to Eaton Pharmaceuticals, Inc. V. Bowen, C.A.6 mination. Brandenfels V. Heckler, C.A.9, 1988, Food and Drug Administration, 1974, 501 F.2d Fiorinal with Codeine No. 1, most studies sub- (Ohio) 1987, 808 F.2d 486, certiorari denied 108 716 F2d 558. 772, 163 U.S.App.D.C. 212. mitted were conducted with old formulation of S.Ct. 68, 484 U.S. 816, 98 L.Ed.2d 32. Under this chapter, before a new drug intend- Where drug manufacturer's submission did Fiorinal with Codeine Nos. 2 and 3, and studies In determining effectiveness of drugs, Com- ed for human use can be marketed in interstate not set forth clearly and concisely the specific failed to measure efficaciousness of certain com- missioner of Food and Drug Administration is commerce, the drug must be clinically tested to provision or provisions in regulations which ponents of drugs. U.S. V. 225 Cartons, More or not required to defer to conclusions of experts establish that it is both safe and effective. Edi- were inapplicable to research dealing with Less, of an Article of Drug, D.N.J.1988, 687 that studies submitted by drug companies are son Pharmaceutical Co., Inc. V. Food and Drug drug's efficacy and did not specify or define F.Supp. 946. adequate and well-controlled and prove effec- Administration, Dept. of Health, Ed., and Wel- alternative procedures which should be used to tiveness of drugs under consideration; both va- fare, 1979, 600 F.2d 881, 195 U.S.App.D.C. 17. test drug's efficacy, neither Food and Drug Ad- 13b. Breast implants lidity of methodology used in particular studies In proceeding on new drug application, sub- ministration nor court could waive regulations Food and Drug Administration (FDA) report and ultimate question of effectiveness are issues stantial evidence supported conclusion of the requiring that efficacy of drug be established by on risks of silicone gel breast implants was for Commissioner to determine. Warner-Lam- Commissioner that, though it might be unethical controlled investigation. Cooper Laboratories, sufficiently reliable to be admissible hearsay as bert Co. V. Heckler, C.A.3, 1986, 787 F.2d 147. to conduct such 8 study comparing two groups Inc. V. Commissioner, Federal Food and Drug product of factual investigation conducted by With respect to application for clearance to of cardiac patients, double-blind controlled test- Administration, 1974, 501 F.2d 772, 168 FDA pursuant to its statutory authority. Toole U.S.App.D.C. 212. market a new animal drug, when Food and Drug ings of the new drug and one of its components V. McClintock, M.D.Ala.1991, 778 F.Supp. 1543. Administration proceeds by way of ad hoc artic- could ethically be performed on noncardiac pa- That causal connection between chloroquine ulation of safety standards, it is incumbent upon tients and that such testing was necessary be- phosphate and chloroquine retinopathy was not 14. Approval of drug-Administrative agen- it to give applicant notice of those standards and fore the drug could be administered to cardiac even suspected in the long term use by humans cy of manner in which the data before it failed to patients. Edison Pharmaceutical Co., Inc. V. of the drug at the time manufacturers tested the Food and Drug Administration has jurisdic- meet them and that notice must be given in Food and Drug Administration, Dept. of Health, drug would not relieve them of negligence in tion to decide with administrative finality, sub- timely fashion to put manufacturer in position to Ed., and Welfare, 1979, 600 F.2d 831, 195 failing to conduct animal studies to show the ject to types of judicial review provided, the dispute Administration's interpretation of the U.S.App.D.C. 17. connection between the drug and the disease. "new drug" status of individual drugs or classes safety criteria, object to Administration's cri- That multiinvestigator clinical trials testing Hoffman V. Sterling Drug, Inc., C.A.Pa.1973, 485 of drugs. Weinberger V. Bentex Pharmaceuti- tique of submitted studies, and conduct and effectiveness of combination drug which con- F.2d 132, on remand 374 F.Supp. 850. cals, Inc., S.C.1973, 98 S.Ct. 2488, 412 U.S. 645, proffer new studies meeting newly articulated tained Dexedrine and amobarbital and which The safety and efficacy of combination drug 37 L.Ed.2d 235. requirements, and, should applicant then identi- was labelled for use with obese patients involved involved in misbranding action cannot be equat- Even though a drug manufacturer does not fy a material issue of fact, Administration must subjects who were anxious, obese patients so ed with the safety of the components separately have any new drug application in effect and is hold hearing. American Cyanamid Co. V. Food that trials provided no assurance that Dexe- or in combination with different ingredients; the not seeking approval of any drugs, the Food and and Drug Administration, 1979, 606 F2d 1307, drine, in amounts contained in drug, produced in fact that one individual component of combina- Drug Administration may make a declaratory 196 U.S.App.D.C. 400. nonanxious, obese patients aide effects capable tion drug may be generally recognized as safe order that a drug is a "new drug" 80 as to Recommendations of the National Academy of of being remedied by amobarbital did not render and effective is not relevant to the issue whether acquire an effective new drug application before Sciences-National Research Council as to effec- trials deficient under Food and Drug regulation the combination itself is 80 recognized. U.S. V. drug may be introduced into commerce; power tiveness of a new drug are advisory in nature. requiring suitability of subjects 80 as to autho- 1,048,000 Capsules, More or Less, D.C.Tex.1972, of the Administration to decide threshold juris- Holland Rantos Co., Inc. V. U.S. Dept. of Health, rize summary, denial of new drug application in 347 F.Supp. 768, affirmed 494 F.2d 1158. dictional question whether the drug is a "new Ed. and Welfare, 1978, 587 F.2d 1173, 190 that present labeling of drug could be altered to Raw manufacturer of DES could not be verti- drug" is not only an incident to its power to U.S.App.D.C. 276. recommend use with anxious, obese patients. cally liable for distribution of DES tablets where approve or withdraw approval of a new drug Food and Drug Administration's disregard, Smithkline Corp. V. Food and Drug Administra- tablet manufacturer bore responsibility of con- application. Weinberger V. Hynson, Westcott without reasons, of recommendation of study tion, 1978, 587 F.2d 1107, 190 U.S.App.D.C. 210. ducting separate test to determine adverse ef- and Dunning, Inc., Va.1973, 93 S.Ct. 2469, 412 group of the National Academy of Sciences- 210 U.S. 609, 37 L.Ed.2d 207. National Research Council that new drug be 21 § 355 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 Note 14 Note 16 considered effective for treatment of vaginitis Health, Ed. and Welfare, 1972, 466 F.2d 455, 151 sue whether drug product is a "new drug" sub- did not constitute sufficient ground to set aside light suggesting that the drug has become un- U.S.App.D.C. 284. ject to provisions of this chapter district court final order denying new drug application where safe, whether or not the drug was generally Commissioner of Food and Drugs has juris- might well stay its hand, awaiting appropriate refusal to accept panel's rating of effectiveness recognized as safe in the interim, a new drug diction, in proceeding to determine whether lack administrative determination of this threshold application remains effective unless it is sus- was essentially judgment that applicant had not yet offered substantial evidence of drug's effec- of effectiveness as claimed makes a drug unmar- jurisdictional question; however, where there is pended. Weinberger V. Hynson, Westcott and tiveness and should be put to its proof and ketable, to decide the threshold question wheth- an administrative determination, whether it be Dunning, Inc., Va.1978, 98 S.Ct. 2469, 412 U.S. er the product in controversy is a "new drug," explicit or implicit in the withdrawal of a new 609, 87 LEd2d 207. where subsequent events vindicated such judg- ment in that application was unable to produce and if the administrative agency takes jurisdic- drug application, the tactic of "reserving" the Substantial evidence supported determination necessary adequate and well-controlled studies tion, the same jurisdictional issue is present for threshold jurisdictional question for later judi- of Commissioner of Food and Drug Administra- of drug's effectiveness. Holland Rantos Co., judicial review on direct appeal from the admin- cial determination is not tolerable. CIBA Corp. tion that use of concomitant medication flawed Inc. V. U.S. Dept. of Health, Ed. and Welfare, istrative decision. Ciba Corp. V. Richardson, V. Weinberger, N.J.1978, 98 S.Ct. 2495, 412 U.S. clinical study of oral proteolytic enzymes and C.A.N.J.1972, 463 F2d 225, affirmed 93 S.Ct. 640, 87 L.Ed.2d 280. 1978, 587 F.2d 1178, 190 U.S.App.D.C. 276. that other studies were in violation of regulatory 2495, 412 U.S. 640, 87 L.Ed.2d 230. Action of Federal Trade Commission in order- Action by pharmaceutical trade association criteria such that withdrawal of approval was ing operations of weight loss clinics to state in In light of Food and Drug Administration's and one of its member companies seeking judi- appropriate. Warner-Lambert Co. V. Heckler, their advertisements that one of the drugs being function of protecting public health and safety, cial review of Food and Drug Administration's C.A.8, 1986, 787 F.2d 147. used was a new drug which had not been deter- "paper new drug application policy" which al- regulation of certain drugs which were treated Manufacturer was not prejudiced by nine-year mined to be effective for obesity did not imper- lows approval of duplicate new drug application as "new drugs," and seeking a judgment declar- delay between request for hearing before Food missibly encroach upon the confidential relation- without examination of raw data when verifica- ing that those drugs were not "new drugs," was and Drug Administration on hair and scalp ship between a physician and a patient; the tion of prior studies has been accomplished properly dismissed on the ground that the mat- products and Food and Drug Administration's FTC order did not affect the right of a physician through scrutiny of scientific community and ter lay within the primary jurisdiction of the withdrawal of approval, where the delay enabled to prescribe or administer the drug for his or which is supported by argument that likelihood Food and Drug Administration, that judicial re- him to continue marketing the products and her patients but merely prevented the weight of fraud or bias existing after years of published view was available only after a formal adminis- where the deaths of doctors who conducted stud- loss clinics from advertising their clinics and studies subject to verification through scrutiny trative ruling, and that, in respect to the prayer les did not prejudice defendant in that the truth weight reduction program in a way which failed of publishing journals and general scientific for declaratory relief, a sound exercise of discre- of their views was not the issue but whether the to disclose that the Food and Drug Administra- community, potential for testing and duplication, tion required the court to refuse to take jurisdic- studies on their face complied with Food and tion had not approved the drug for such use. and experience of drug's performance once it tion. National Ethical Pharmaceutical Ass'n V. Drug Administration guidelines. Brandenfels V. Simeon Management Corp. V. F.T.C., C.A.9, has been on market, becomes vastly diminished, Weinberger, C.A.S.C.1974, 503 F.2d 1061. Heckler, C.A.9, 1983, 716 F.2d 553. 1978, 579 F.2d 1187. is valid. Upjohn Mfg. Co. V. Schweiker, D.C.Mich.1981, 520 F.Supp. 58, affirmed 681 Determination of Court of Appeals reviewing Manufacturers of drug were entitled to notice A new drug may not be introduced into inter- F.2d 480. decision of Commissioner of Food and Drugs of specific grounds on which the Food and Drug state commerce unless an application has been that a drug is a "new drug" within meaning of Administration proposed to withdraw approval filed with and approved by the Food and Drug Determination of actual safety and effective- this section providing for exclusion of new drugs of the drug's new drug application and to an Administration; the FDA may not approve a ness of drug product is committed to Food and from market unless proven effective as claimed opportunity to submit evidence which would en- new drug application unless it finds that there is Drug Administration due to its superior access is reviewable by the Supreme Court, and it is title them to a hearing before an order of with- substantial evidence that the drug is effective to technical expertise. U.S. V. Articles of Drug not appropriate that a district court entertain a drawal could be validly issued. Sterling Drug for the labeled use. Simeon Management Corp. HORMONIN, D.C.N.J.1980, 498 F.Supp. separate suit by the loser in the administrative Inc. V. Weinberger, C.A.2, 1974, 503 F.2d 675. V. F.T.C., C.A.9, 1978, 579 F.2d 1137. 424, affirmed 672 F.2d 902, 904. proceeding for a redetermination of the same If court finds that Food and Drug Administra- Under this subchapter, ultimate determination Determination of whether product constituted question. Ciba Corp. V. Richardson, C.A.N.J. tion's order withdrawing drug from market of safety of a drug is not a matter given to the a "new drug" requiring filing and approval of a 1972, 463 F.2d 225, affirmed 93 S.Ct. 2495, 412 identified defects which conclusively rendered courts, but one to be determined by the Food new drug application was within the primary U.S. 640, 37 L.Ed.2d 230. each piece of evidence submitted in support of and Drug Administration upon submission of a jurisdiction of the Food and Drug Administra- The Food and Drug Administration had pri- drug's efficacy as being inadequate or uncon- new drug application. U.S. V. 1,048,000 Cap- tion, precluding district court review until final mary jurisdiction to determine whether each trolled in light of permit regulations, court must sules, More or Less, "Afrodex", C.A.Tex.1974, agency action and exhaustion of administrative drug named in applicants' complaint was "new affirm order. Cooper Laboratories, Inc. V. 494 F.2d 1158. remedies. IMS Ltd. V. Califano, D.C.Cal.1977, drug" and, following such administrative deter- Commissioner, Federal Food and Drug Admin- 453 F.Supp. 157. Order of Commissioner of Food and Drugs mination, applicants would then be entitled to istration, 1974, 501 F.2d 772, 163 U.S.App.D.C. Since the Federal Drug Administration has 212. withdrawing approval of line of drugs for inter- seek judicial review. National Ethical Pharma- state marketing was not supported by adequate failed to act in contemplation of what Congress ceutical Ass'n V. Weinberger, D.C.S.C.1978, 365 Standard of review to be applied to order of findings and conclusions, where order merely intended in this section, the Administration and F.Supp. 735, affirmed 503 F.2d 1051. the Food and Drug Administration denying an tracked language of this section, stating in con- Department of Health, Education and Welfare Determination by Food and Drug Administra- evidentiary hearing on effectiveness of drug pre- clusory terms that there was lack of substantial would be found to have in fact disapproved the tion that a product is "new drug" or a "me-too" vioualy approved for marketing solely on demon- evidence that the drugs were effective, and did use of laetrile for treating cancer, and the dis- drug is reviewable. National Ethical Pharma- stration that it was safe for its intended use is not disclose evidence upon which the Commis- trict court, for want of action on the part of the ceutical Ass'n V. Weinberger, D.C.S.C.1978, 365 whether deficiencies found in the studies submit- aioner based his judgment. USV Pharmaceuti- agencies, had jurisdiction of class action brought F.Supp. 735, affirmed 503 F.2d 1051. ted by manufacturer of the drug conclusively cal Corp. V. Secretary of Health, Ed. and Wel- by cancer victims and their spouses seeking an render the studies inadequate. E. R. Squibb & fare, 1972, 466 F.2d 455, 151 U.S.App.D.C. 284. order directing the Administration to desist 15a. Timeliness Sons, Inc. V. Weinberger, C.A.3, 1973, 483 F.2d from precluding the administration of laetrile to Where Commissioner of Food and Drugs had Writ of mandamus would not issue to compel 1382. failed to name hearing examiner in response to patients in the United States suffering from Food and Drug Administration to expedite pro- Satisfactory adjudication of appeal from denial drug manufacturer's demand and delayed more cancer. Rutherford V. U.S., D.C.Okl1975, 399 cessing of application for approval of generic by the Food and Drug Administration of eviden- F.Supp. 1208, affirmed and remanded on other than two months in responding to manufactur- drug, following expiration of statutory period tiary hearing on effectiveness of drug which had er's request, filed two years later, for a stay grounds 542 F.2d 1137, on remand 424 F.Supp. during which decision was to be made; while been previously approved on the basis of safety 105. pending decision in manufacturer's action for judicial intervention might benefit applicant, only mandated that a meaningful comparison be declaratory judgment that its drugs were not Whether drugs are "new" or "old" requires there would be corresponding harm to other made by the FDA between the study submitted new drugs, Commissioner's precipitous sum- determination by the Food and Drug Adminis- applicants whose processing would be further in the instant case and study held sufficient by mary withdrawal of approval of previously tration as to whether they are generally recog- delayed. In re Barr Laboratories, Inc., 1991, the Supreme Court, and also mandated amplifi- granted new drug applications were arbitrary. nized, among qualified experts, as safe and ef- 930 F.2d 72, 289 U.S.App.D.C. 187, certiorari cation and clarification in light of highly esoteric USV Pharmaceutical Corp. V. Secretary of fective for their intended use. National Ethical denied 112 S.Ct. 297, 298, 116 L.Ed.2d 241. and scientific terms employed in the information Health, Ed. and Welfare, 1972, 466 F.2d 455, 151 Pharmaceutical Ass'n V. Weinberger, D.C.S.C. before the court. E. R. Squibb & Sons, Inc. V. U.S.App.D.C. 284. 1973, 365 F.Supp. 785, affirmed 503 F.2d 1051. 16. Withdrawal of approval Weinberger, C.A.S, 1973, 483 F.2d 1382. Under this chapter as originally enacted, Issue of whether drug is actually safe and 15. Judicial Action of Food and Drug Administration which empowers the Food and Drug Adminis- effective is for the Food and Drug Administra- (FDA) in rescinding its approval of manufactur- In cases where there has been no formal tion. USV Pharmaceutical Corp. V. Secretary of tration to withdraw approval of a new drug er's application to make and sell new drug, on administrative determination of jurisdictional is- application whenever new evidence comes to ground that approval had been issued through 212 213 21 8 355 FOOD AND DRUGS FOOD AND DRUGS Note 16 21 § 355 Note 17a inadvertent mistake, was not so clearly ultra tion because of lack of substantial evidence of vires as to justify disregard of exclusive jurisdic- appropriate to require Commissioner, as an ex- efficacy of drug when it is apparent at threshold issue of fact which would justify a hearing. tion of Court of Appeals and intervention by ception to usual case, whichever way he decides that applicant has not tendered any evidence U.S.V. V. Pharmaceutical Corp. V. Secretary of district court; even if right vested, manufactur- threshold issue, to hold a full evidentiary hear- which on its face meets statutory standards as Health, Ed. and Welfare, 1972, 466 F.2d 455, 151 er was not deprived of factual hearing to prove ing on "all" relevant issues relating to approva- particularized by regulations, appropriate. U.S.App.D.C. 284. its qualifications to make and sell drug, and bility of new drug application, where drug manu- Weinberger V. Hynson, Westcott and Dunning, In circumstance in which the Food and Drug postdenial hearing met due process require- Inc., Va.1978, 98 S.Ct. 2469, 412 U.S. 609, 37 facturer had first filed new drug application over Administration publishes in Federal Register ments. American Therapeutics, Inc. V. Sullivan, L.Ed.2d 207. six years prior thereto and in the interim its the required notice to drug manufacturers of D.D.C.1990, 755 F.Supp. 1. application had been denied on three separate Due process does not demand a hearing on opportunity for hearing and proposed withdraw- occasions without an opportunity for hearing Proposed withdrawal of approval of new drug proposed withdrawal of an effective new drug al of drugs from market and manufacturers then despite direction to contrary from court. Edi- applications in effect for drug is not a final order application because of lack of substantial evi- fail to avail themselves of opportunity for the son Pharmaceutical Co., Inc. V. Food and Drug and is not ordinarily reviewable in district court. dence of efficacy of drug when it appears conclu- hearing within required 30 days, withdrawal of Administration, Dept. of Health, Ed. and Wel- Sterling Drug, Inc. V. Weinberger, D.C.N.Y. sively from applicant's pleadings that it cannot drugs from market is required by this section fare, 1975, 513 F.2d 1068, 16 U.S.App.D.C. 273, 1974, 384 F.Supp. 557, affirmed 509 F.2d 1236. succeed. Weinberger V. Hynson, Westcott and governing withdrawal of drugs and is purely a rehearing denied 517 F.2d 164, 170 U.S.App. Secretary of Health, Education, and Welfare Dunning, Inc., Va.1973, 93 S.Ct. 2469, 412 U.S. ministerial duty, and failure to withdraw consti- D.C. 350. 609, 37 L.Ed.2d 207. tutes agency action unlawfully withheld. Ameri- must, under this section and section 357 of this The Food and Drug Administration may with- can Public Health Ass'n. V. Veneman, D.C.D.C. title governing withdrawal of antibiotic and no- Food and Drug Administration's denial of ad- draw a drug from the market without a hearing 1972, 349 F.Supp. 1311. nantibiotic drugs, upon finding of lack of sub- judicatory hearing on application for clearance when, and only when, it appears conclusively stantial evidence that the drugs have effect they to market a new animal drug will be upheld if from the applicants "pleadings" that the new Hearing on withdrawal of a new drug applica- are represented to have under conditions of use Administration identifies at least one conclusive tion is to be scheduled as soon as practicable drug application cannot succeed. Sterling Drug prescribed, recommended or suggested in label- deficiency in each of tests proffered, but if stud- after request by drug manufacturers for such a Inc. V. Weinberger, C.A.2, 1974, 508 F.2d 675. ing, begin procedures to withdraw a drug when ies adopting all reasonably applicable methods of hearing; and, while some agency discretion is he concludes that there is no substantial evi- Word "applicant" or "respondent" in subsec. showing drug's safety have not been conclusively conferred in scheduling the hearing, intermina- (g) of this section refers only to holders of new- dence of efficacy rather than thereafter granting demonstrated to be inadequate, Administration ble delay is not contemplated. American Public drug applications; thus, said subsection did not manufacturers time to bolster record regarding must hold a hearing. American Cyanamid Co. Health Ass'n. V. Veneman, D.C.D.C.1972, 349 V. Food and Drug Administration, 1979, 606 require Secretary personally to notify drug man- the drug's effectiveness. American Public F.Supp. 1811. Health Ass'n V. Veneman, D.C.D.C.1972, 849 F.2d 1307, 196 U.S.App.D.C. 400. ufacturers which produced anorectic drugs con- taining amphetamines and which did not hold 17a. Jurisdiction F.Supp. 1811. Food and Drug Administration would have new-drug applications covering combination am- Jurisdictional question whether a drug prod- Invocation of emergency procedure to imme- valid ground for denying hearing on application phetamine products of hearing regarding Secre- uct is a "new drug," which is defined in section diately suspend drugs which present an immi- for clearance to market a new animal drug if tary's withdrawal of approval of such applica- 321 of this title as a drug not generally recog- nent hazard to the public health is matter which Administration's interpretation and application tions. North American Pharmacal, Inc. V. De- nized among experts is effective as well as safe is peculiarly one of judgment. American Public of statutory safety standards are unimpeachable. partment of Health, Ed. and Welfare, C.A.8, for its intended uses, involves a determination of Health Ass'n V. Veneman, D.C.D.C.1972, 349 American Cyanamid Co. V. Food and Drug Ad- 1973, 491 F2d 546. technical and scientific questions by experts, and F.Supp. 1811. ministration, 1979, 606 F.2d 1307, 196 U.S.App. Publication in Federal Register of notice of agency is therefore appropriately the arm of D.C. 400. 16a. Insurance hearing regarding the withdrawal of approval of government to make threshold determination of Only if drug manufacturer has had fair oppor- new-drug applications covering combination am- issue of coverage. CIBA Corp. V. Weinberger, Notwithstanding provisions in health insur- tunity to dispute newly articulated safety stan- phetamine products gave manufacturers, which N.J.1973, 93 S.Ct. 2495, 412 U.S. 640, 37 ance policy providing that policy was to be inter- dards of Food and Drug Administration and to produced anorectic drugs containing amphet- L.Ed.2d 230. preted in accordance with laws of District of resubmit compliant tests, or if original tests amines and which did not hold new-drug applica- Food and Drug Administration has jurisdic- Columbia where laetrile was illegal, insured, conclusively failed to meet general statutory tions covering combination amphetamine prod- tion in an administrative proceeding on proposed who was terminally ill, who received laetrile prerequisites, may Food and Drug Administra- ucts, sufficient opportunity to be heard; and withdrawal of an effective new drug application treatments in Oklahoma under specific authority tion deny hearing on basis of methodology of failure personally to notify each manufacturer of because of lack of substantial evidence of effica- under an order of United States district court research relied upon by manufacturer. Ameri- hearing did not deprive them of due process. cy to determine jurisdictional question whether and who complied with policy's requirements can Cyanamid Co. V. Food and Drug Adminis- North American Pharmacal, Inc. V. Department a drug product is a "new drug" within this with regard to establishing her claim, was enti- tration, 1979, 606 F.2d 1307, 196 U.S.App.D.C. of Health, Ed. and Welfare, C.A.8, 1973, 491 chapter which defines a new drug as a drug not tled to have laetrile treatments paid for by 400. F.2d 546. generally recognized among experts as effective insurer as covered medical expenses. Wilson V. Under this chapter, it is contemplated that a Travelers Ins. Co., Okl.1980, 605 P.2d 1327. Petitioner was not entitled to hearing before as well as safe for its intended uses. CIBA new drug will be approved or disapproved on Commissioner on question of whether or not its Corp. V. Weinberger, N.J.1973, 98 S.Ct. 2495, 17. Hearing the basis of scientific tests contained in the new product constituted new animal drug within 412 U.S. 640, 37 L.Ed.2d 230. Food and Drug Administration's so-called ad- drug application; the hearing offers an opportu- meaning of this section. Agri-Tech, Inc. V. Rich- Food and Drug Administration has jurisdic- nity to test the strength and credibility of this ministrative summary judgment procedure, ardson, C.A.8, 1973, 482 F.2d 1148. tion to decide "new drug" status of product and material. Edison Pharmaceutical Co., Inc. V. whereby it will not provide a formal hearing on Opportunity to be heard administratively is district court may refer new drug issue to Food Food and Drug Admin., Dept. of Health, Ed. not prerequisite to prosecution for introduction and Drug Administration for resolution, but proposed withdrawal of an effective new drug and Welfare, 1979, 600 F.2d 831, 195 U.S.App. application because of lack of substantial evi- D.C. 17. of a "new drug" into interstate commerce with- court may exercise its concurrent jurisdiction to adjudicate status of product. Premo Pharma- dence of efficacy of drug when it is apparent at out approval of a new drug application. Durovic threshold that applicant has not tendered any Though a new drug applicant may present V. Richardson, C.A.T11.1973, 479 F.2d 242, certio- ceutical Laboratories, Inc. V. U.S., C.A.N.Y.1980, evidence which on its face meets statutory stan- testimony or evidence at the hearing to show rari denied 94 S.Ct. 232, 414 U.S. 944, 38 629 F.2d 795. dards as particularized by regulations, is valid. that the studies and data submitted with the L.Ed.2d 168, rehearing denied 94 S.Ct. 611, 414 Limited "new drug" issue was sufficiently Weinberger V. Hynson, Westcott and Dunning, new drug application in fact constitute the ade- U.S. 1088, 38 L.Ed.2d 494. clear to warrant district court's exercise of its Inc., Va.1973, 98 S.Ct. 2469, 412 U.S. 609, 37 quate tests and substantial evidence necessary for new drug approval, the applicant cannot Where drug manufacturer's applications for subject-matter jurisdiction, especially where to L.Ed.2d 207. marketing a line of drugs had been approved refer issue to Food and Drug Administration at submit new studies at the hearing to be consid- ered in the first instance by the administrative pursuant to prior law but Commissioner of Food the late date would be wasteful and duplicative. This section and regulations issued thereun- der, which express well-established principles of law judge; to do 80 would effectively shield an and Drugs proposed, without a hearing, to with- Premo Pharmaceutical Laboratories, Inc. V. draw that approval on basis of a new standard U.S., C.A.N.Y.1980, 629 F.2d 795. scientific investigation, in their reduction of applicant's data from the initial scrutiny of staff "substantial evidence" standard to detailed and new information, together with evidence Decision of Commissioner that Laetrile is a experts. Edison Pharmaceutical Co., Inc. V. guidelines for protection of public, make Food Food and Drug Admin., Dept. of Health, Ed. available when approval was originally granted, "new drug" subject to premarketing approval and Drug Administration's so-called administra- and Welfare, 1979, 600 F.2d 831, 195 U.S.App. it was incumbent upon Commissioner, before under this chapter was properly within Food tive summary judgment procedure, whereby the D.C. 17. calling upon manufacturer for additional evi- and Drug Administration's primary jurisdiction. FDA will not provide a formal hearing on pro- On hearing to determine threshold issue of dence establishing a right to a hearing, to state Carnohan V. U.S., C.A.Cal.1980, 616 F.2d 1120. posed withdrawal of effective new drug applica- safety of double-blind tests for new drug, it was facts and reasons showing at least prima facie Initial determination of whether drug is new that the evidence before him raised no material animal drug is within jurisdiction of Commis- 214 215 21 8 355 FOOD AND DRUGS Note 17a FOOD AND DRUGS 21 § 355 Note 22 sioner, and he may summarily deny hearing on D.C.Mich.1981, 520 F.Supp. 58, affirmed 681 issue whether drug is generally "recognized" F.2d 480. suit brought by individual against drug compa- Food and Drug Administration could not ban and therefore exempt from withdrawal provi- ny, on behalf of himself and other purchasers of use of laetrile under grandfather clause if in fact Threat of injury to plaintiffs, whose claim was sions if he finds there is no "substantial evi- allegedly ineffective drugs to recover money laetrile had been used prior to the cutoff date in not that they would in fact consume unsafe or dence" raising issue of fact. Agri-Tech, Inc. V. spent in purchase of such drugs and to obtain treatment of cancer and without ill effect, It was ineffective drugs, but that they were being sub- Richardson, C.A.8, 1978, 482 F.2d 1148. punitive damages. Consumer Federation of not necessary that the drug be shown to have jected to risk to their health on account of America V. Upjohn Co., D.C.App.1975, 846 A.2d been effective in treatment of cancer. Ruther- Since Congress has created primary jurisdic- marketing of Category III drugs, was both real 725. tion in Food and Drug Administration to deter- ford V. U.S., D.C.Okl.1977, 429 F.Supp. 506. and immediate and, hence, was sufficient to give mine in first instance safety and efficacy of new plaintiffs standing in suit for declaratory and 19. Res judicata 21. Burden of proof drug with such administrative determinations injunctive relief against regulations of Food and Doctrine of res judicata did not preclude Fed- Proponents of laetrile did not conduct the subject to review in appropriate court of ap- Drug Administration governing the over-the- eral Food and Drug Administration from pro- research and laboratory testing required under peals, as a jurisdictional matter district courts counter drug market. Cutler V. Kennedy, ceeding to withdraw approval of drug on theory prevailing agency procedures and by this chap- have no role to play in determining whether a D.C.D.C.1979, 475 F.Supp. 838. that drug had not been proved effective as sin- ter, thus, they did not meet their burden to new drug should be approved by Food and Drug Action wherein plaintiff consumers challenged gle active component drug, though administra- fulfill premarketing requirements. Rutherford Administration. Hanson V. U.S., D.C.Minn.1976, regulations adopted by Food and Drug Adminis- tion had previously determined that drug had V. U.S., C.A.Okl.1980, 616 F.2d 455, certiorari 417 F.Supp. 30, affirmed 540 F.2d 947. tration for policing the nation's over-the-counter not been shown to be effective as fixed combina- denied 101 S.Ct. 836, 449 U.S. 987, 66 L.Ed.2d Under section 1337 of Title 28 giving the drug market met the ripeness requirement in tion drug. Sterling Drug Inc. V. Weinberger, 160. district courts original jurisdiction of any civil that the issue whether the regulations were C.A.N.Y.1975, 509 F.2d 1236. Where Federal Trade Commission sought an action or proceeding arising under any act of consistent with the statutory scheme pursuant 20. Estoppel order requiring weight loss clinics to disclose in Congress regulating commerce, the district to which they were promulgated was fit for their advertisements the fact that one of the court had jurisdiction of class action brought judicial resolution and both litigants would suf- Drug manufacturer could be collaterally es- drugs being used in the program was a new against the United States and the Secretary of fer a hardship from further delay in resolving topped from litigating, in seizure proceeding, drug which had not been determined by the Health, Education and Welfare by cancer vic- that issue. Cutler V. Kennedy, D.C.D.C.1979, whether Fiorinal with codeine was "new drug" Food and Drug Administration to be effective time, and their spouses, seeking an order direct- 475 F.Supp. 838. that could not be marketed without Food and for obesity, FTC did not have the burden of ing the Federal Drug Administration to desist Where individual and corporate defendant had Drug Administration (FDA) approval, in view of proving that the weight loss clinics' program from precluding the administration of laetrile to actual notice that Food and Drug Administra- determination in prior seizure proceeding con- was unsafe or ineffective. Simeon Management patients in the United States suffering from tion considered subject drugs "new drugs" and cerning related drugs that differed only in Corp. V. F.T.C., C.A.9, 1978, 579 F.2d 1137. cancer, as the prohibiting language of this sec- knew that there was no effective new drug amount of codeine they contained; amounts of application permitting sale of subject drugs, de- codeine in drugs was immaterial to new drug Those who seek to market a drug or food tion stems from and has to do with commerce powers of the United States, and as plaintiffs fendants were not entitled to claim that this determination, factual and legal issues in pro- additive in interstate commerce have some bur- section prohibiting sale of new drugs without ceedings were almost identical, findings of other den of proving the safety and, for drugs, the were being precluded from transporting laetrile in commerce. Rutherford V. U.S., D.C.Okl.1975, approval of new drug application by FDA was court were necessary to outcome of prior pro- effectiveness of their product. U.S. V. Articles 399 F.Supp. 1208, affirmed and remanded on unconstitutionally vague and could not support a ceeding, and manufacturer had full and fair op- of Food and Drug Consisting of Coli-Trol 80, conviction. U.S. V. Marcen Laboratories, Inc., portunity to litigate in other proceeding. U.S. V. F4C-60 Feed Grade, Entrol-S Medicated, En- other grounds 542 F.2d 1137, on remand 424 D.C.N.Y.1976, 416 F.Supp. 453, affirmed 556 Sandoz Pharmaceuticals Corp., C.A.6 (Ohio) trol-P, C.A.Ga.1975, 518 F.2d 743. F.Supp. 105. F.2d 562. 1990, 894 F.2d 825, certiorari denied 111 S.Ct. Those who seek to market a drug or food 18. Persons entitled to bring suit 45, 498 U.S. 810, 112 L.Ed.2d 21. additive in interstate commerce have some bur- Drug company met "zone of interests" test for As the named plaintiff, a cancer victim, and those similarly situated were wholly without Prior litigation between consumers of over- den of proving the safety and, for drugs, the prudential standing to bring action to prevent the-counter drugs and Food and Drug Adminis- effectiveness of their product. U.S. V. Articles Food and Drug Administration (FDA) from ap- means or resources to comply with provisions of tration in which it was determined that consum- of Food and Drug Consisting of Coli-Trol 80, proving generic versions of Intal Nebulizer Solu- this section pertaining to filing an application tion (eromolyn) without requiring specific test- with the Secretary of Health, Education and ers had standing to challenge Food and Drug F4C-60 Feed Grade, Entrol-S Medicated, En- Welfare for approval to introduce a new drug Administration's regulations, which went unap- trol-P, C.A.Ga.1975, 518 F.2d 743. ing, as Congress intended Hatch-Waxman into interstate commerce, the named plaintiff pealed by Food and Drug Administration, pre- Burden is on sponsor of new drug to demon- Amendments which govern FDA's approval of cluded Food and Drug Administration from at- strate its safety and effectiveness. Edison applications for generic versions of pioneer and those similarly situated, in being thus de- tempting to assert that consumers had no stand- Pharmaceutical Co., Inc. V. Food and Drug Ad- drugs to benefit pioneer drug manufacturers. nied freedom of choice for treatment by the ing to challenge rule implementing Food, Drug, ministration, Dept. of Health, Ed. and Welfare, Fisons Corp. V. Shalala, D.D.C.1994, 860 F.Supp. drug laetrile to alleviate or cure their cancer, and Cosmetic Act, under doctrine of collateral 1975, 518 F.2d 1063, 168 U.S.App.D.C. 273, re- 859. were deprived of life, liberty or property without estoppel, in absence of evidence of change in due process of law. Rutherford V. U.S., hearing denied 517 F.2d 164, 170 U.S.App.D.C. Claim of AIDS (Acquired Immunodeficiency controlling facts sufficient to justify exception to 350. D.C.Okl.1975, 899 F.Supp. 1208, affirmed and Syndrome) sufferer that drug manufacturer and collateral estoppel principles. Cutler V. Hayes, remanded on other grounds 542 F.2d 1187, on Drug manufacturers must carry burden of university acted illegally when they terminated 1987, 818 F.2d 879, 260 U.S.App.D.C. 230. remand 424 F.Supp. 105. showing by substantial evidence the claimed effi- investigation into use of drug Ampligen as treat- Since Food and Drug Administration had no Consumer organizations were without stand- cacy and safety of drugs. North American ment for the disease and ceased providing him authority to approve marketing of drug product Pharmacal, Inc. V. Department of Health, Ed. with the drug as part of their clinical studies did ing to institute suit against drug companies on without new drug application, Government was and Welfare, C.A.8, 1973, 491 F.2d 546. not arise under the Federal Food, Drug, and behalf of themselves, their members and all not estopped from asserting that that drug other purchasers of certain allegedly ineffective Physicians and patients challenging, by way of Coametic Act 80 as to give court jurisdiction product and related product were "new drugs" drugs to recover money spent by purchasers of petition for preliminary injunction, decision of over his claim as the civil action arising under an under section 321 of this title. U.S. V. Articles act of Congress regulating commerce. DeVito such drugs and to obtain punitive damages Secretary suspending new drug applications for of Drug HORMONIN, D.C.N.J.1980, 498 V. HEM, Inc., M.D.Pa.1988, 705 F.Supp. 1076. where such organizations had not purchased any phenformin hydrochloride on ground that drug F.Supp. 424, affirmed 672 F.2d 902, 904. of drugs involved and had not themselves been posed an "imminent hazard" had burden of dem- Drug manufacturer which marketed drug un- injured in fact, and where individualized proof United States was not estopped from bringing onstrating substantial likelihood that decision der trademark and which filed pioneer new drug would be necessary to establish each particular an enforcement proceeding to prevent further was a clear error of judgment and that he failed application for that drug had standing to file purchase and resulting damages incurred by shipment of drug X-Otag Plus in interstate to articulate any rational connection between action challenging Food and Drug Administra- each member and individual damage claims commerce without first obtaining an approved facts submitted to him and choice he made. tion's approval of new drug application to Brit- would be governed by common law of each state new drug application or abbreviated new drug Forsham V. Califano, D.C.D.C.1977, 442 F.Supp. ish manufacturer and distributor of drug called in which drug sales took place. Consumer Fed- application despite claim that, because of refusal 203. "ibuprofen" on its claim of competitive market eration of America V. Upjohn Co., D.C.App.1975, of Food and Drug Administration to follow its position and its claim that trade secret data and 346 A.2d 725. own regulations, abbreviated new drug applica- 22. Evidence information contained in its pioneer new drug tion submitted by manufacturer for X-Otag "Substantial evidence," as used in this section, application was made subject to public disclo- 18a. Discretion of court Plus was rejected. U.S. V. X-Otag Plus Tab- which directs the Food and Drug Administration sure due to approval of challenged new drug Trial court did not abuse its discretion in lets, D.C.Colo.1977, 441 F.Supp. 105, affirmed in to refuse approval of a new drug application or application. Upjohn Mfg. Co. V. Schweiker, diamissing, on forum non conveniens grounds, part, remanded in part, on other grounds 602 to withdraw any prior approval if substantial F.2d 1387. 216 evidence that the drug is effective for its intend- 917 21 § 355 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 Note 22 Note 25 ed use is lacking, means adequate and well- Substantial evidence of effectiveness is a nec- adequate and well-controlled studies of product controlled investigations from which experts Health, Ed. and Welfare, 1979, 600 F.2d 831, 195 essary but not a sufficient condition for approval itself or by adequate and well-controlled studies may conclude that the drug will have the U.S.App.D.C. 17. of a new drug application. Edison Pharmaceuti- which concern another drug with same active claimed effect. CIBA Corp. V. Weinberger, N.J. cal Co., Inc. V. Food and Drug Administration, ingredients and which demonstrate bioequiva- At hearing on new drug application, adminis- 1973, 98 S.Ct. 2495, 412 U.S. 640, 37 L.Ed.2d 1975, 517 F.2d 164, 170 U.S.App.D.C. 850. lence of product and other drug. U.S. V. Unde- trative law judge correctly excluded evidence of 280. termined Quantities of an Article of Drug tests that were not submitted with the new drug Meaning of label is relevant to general recog- Phrase "lack of substantial evidence," in this nition of safety of alleged new drug. U.S. V. (Anucort HC Suppositories), D.N.J.1987, 709 application where the drug manufacturer had section which directs Food and Drug Adminis- F.Supp. 511, affirmed 857 F.2d 1464, 1466, cer- failed to invoke the regulation which provides a 1,048,000 Capsules, More of Less, "Afrodex," tration to refuse approval of a new drug applica- C.A.Tex.1974, 494 F.2d 1158. tiorari denied 109 S.Ct. 864, 488 U.S. 1040, 102 procedure for filing new studies. Edison Phar- tion and to withdraw any prior approval if sub- Evidence supported order of Food and Drug L.Ed.2d 988. maceutical Co., Inc. V. Food and Drug Admin., Dept. of Health, Ed. and Welfare, 1979, 600 F.2d stantial evidence that drug is effective for its Administration withdrawing approval of new- Even if substantial evidence to support gener- 831, 195 U.S.App.D.C. 17. intended use is lacking, is not applicable only to drug applications covering combination amphet- al recognition of safety and effectiveness of a proof of actual effectiveness of drugs that fall amine products. North American Pharmacal, combination drug exists concerning the individu- At hearing on new drug application, adminis- within definition of a new drug; hurdle of "gen- al components of the drug, there must also be trative law judge properly excluded as irrelevant Inc. V. Department of Health, Ed. and Welfare, eral recognition" of effectiveness requires at substantial evidence of the safety and efficacy of evidence concerning different treatment which C.A.8, 1978, 491 F.2d 546. least substantial evidence of effectiveness for approval of a new drug application. Weinberger Evidence warranted submission to jury of is- the combination of the generally recognized the Administration allegedly gave to another drug. Edison Pharmaceutical Co., Inc. V. Food components in order for the combination drug to V. Hynson, Westcott and Dunning, Inc., Va.1973, sue of whether "Aralen" (chloroquine phosphate) was sold for use in the treatment of lupus transcend "new drug" status. U.S. V. Articles of and Drug Admin., Dept. of Health, Ed. and 98 S.Ct. 2469, 412 U.S. 609, 37 L.Ed.2d 207. erythematosus without adequate testing to de- Drugs HORMONIN, D.C.N.J.1980, 498 Welfare, 1979, 600 F2d 831, 195 U.S.App.D.C. 17. Evidence submitted by drug manufacturer termine possible harmful side effects. Hoffman F.Supp. 424, affirmed 672 F2d 902, 904. with respect to efficacy of drug for use in treat- V. Sterling Drug, Inc., C.A.Pa.1973, 485 F.2d Plaintiffs, who sought to establish their stand- 24. Questions of fact ment of premature labor and habitual abortion, 132, on remand 874 F.Supp. 850. ing as consumers to challenge regulations Factual question as to whether double-blind including a list of literature references, a copy of an unpublished study, and a representative sam- The "substantial evidence" standard as set out adopted by the Food and Drug Administration tests for new drug were too dangerous to per- ple testimonial letter on behalf of the drug, was in this section and regulation with respect to with respect to policing the nation's over-the- form was a sufficiently material fact in dispute showing required by manufacturers of drugs is counter drug market, were not required, to require an evidentiary hearing on drug manu- sufficient to warrant a hearing on proposed through independent research, to monitor the facturer's new drug application before Commis- withdrawal of effective new drug application be- directed only to question of efficacy, and a dif- cause of lack of substantial evidence of efficacy ferent standard applies where question of safety Federal Register or similar means to keep aioner could issue a final order. Edison Phar- arises, and such different standard should be abreast of precisely which of the thousands of maceutical Co. Inc. V. Food and Drug Adminis- of the drug. Weinberger V. Hynson, Westcott and Dunning, Inc., Va.1973, 93 S.Ct. 2469, 412 articulated by the Food and Drug Administra- the over-the-counter drug products contained tration, Dept. of Health, Ed. and Welfare, 1975, tion. E. R. Squibb & Sons, Inc. V. Weinberger, conditions classifying Category III since such 513 F.2d 1063, 168 U.S.App.D.C. 273, rehearing U.S. 609, 87 L.Ed.2d 207. C.A.3, 1973, 483 F.2d 1382. efforts would not alleviate the injury to their denied 517 F.2d 164, 170 U.S.App.D.C. 350. To prevail at a Food and Drug Administration statutory interests any more than would decision hearing on proposed withdrawal of an effective Evidence that drug was, prior to Oct. 9, 1962, Whether Federal Food and Drug Administra- to forgo the use of the drugs altogether. Cutler new drug application because of lack of substan- effective date of amendments to provisions of tion had new information which would justify V. Kennedy, D.C.D.C.1979, 475 F.Supp. 838. tial evidence of efficacy, applicant must furnish this chapter, prescribed and enthusiastically en- withdrawal of approval of new drug application Fact that much of the raw data used by in effect for prescription drug was factual deter- evidence stemming from adequate and well-con- dorsed by a few physicians in one city and sold trolled investigations. Weinberger V. Hynson, to no more than 150 to 200 doctors in two or Bureau of Drugs in arriving at its conclusion mination to be made first by the Administration. three neighboring states was insufficient to es- that drug posed an imminent hazard had been Sterling Drug Inc. V. Weinberger, C.A.N.Y.1975, Westcott and Dunning, Inc., Va.1978, 93 S.Ct. available for some length of time did not pre- 509 F.2d 1236. 2469, 412 U.S. 609, 37 L.Ed.2d 207. tablish that the drug was generally recognized as safe on the date in question, and thus drug clude use of data in finding imminent hazard Affidavits stating that particular disease that Drug manufacturer's attempt to replace evi- was not entitled to "grandfather clause" exemp- where magnitude of drug's risk was determined drug was marketed as treatment for was hard to dence of controlled investigation with testimony tion from present requirement of this chapter only after extensive reevaluation of data follow- diagnose. ran variable course, and caused pain relating to personal experiences or clinical im- that drug not be shipped in interstate commerce ing hearing. Forsham V. Califano, D.C.D.C. did not create factual question requiring Food pressions arising from use of proposed new drug without prior approval of a new drug application 1977, 442 F.Supp. 203. and Drug Administration to conduct hearing as was inconsistent with this chapter as well as unless it is generally recognized as both safe and Even though testimony of general practition- to whether testimonials of experienced physi- with accompanying regulations and explicit Su- effective. U.S. V. An Article of Drug ers as to safety or efficacy of drugs may be less cians, rather than controlled studies, should be preme Court precedent. Edison Pharmaceutical "Bentex Ulcerine", C.A.Tex.1972, 469 F.2d 875, than compelling, court will not reject all clinical recognized as substantial evidence of drug's effi- Co., Inc. V. Food and Drug Admin., Dept. of certiorari denied 93 S.Ct. 2772, 412 U.S. 938, 37 impressions by general practitioners in suit to cacy. Cooper Laboratories, Inc. V. Commission- Health, Ed. and Welfare, 1979, 600 F.2d 831, 195 L.Ed.2d 397. condemn misbranded drug. U.S. V. 1,048,000 er, Federal Food and Drug Administration, U.S.App.D.C. 17. Decision of Commissioner of Food and Drugs Capsules, More or Less, D.C.Tex.1972, 347 1974, 501 F.2d 772, 163 U.S.App.D.C. 212. Substantial evidence including the testimony relating to marketing order entered after a F.Supp. 768, affirmed 494 F.2d 1158. Whether drug manufacturers violated this of three expert witnesses supported decision of hearing will be upheld and sustained by any Evidence in suit to condemn allegedly mis- section by not submitting new drug application the Commissioner that both animal studies and substantial evidence, but in determining whether branded drugs was insufficient to meet claim- to Food and Drug Administration for "Aralen," clinical testing offered by drug manufacturer in Commissioner acted within limits of discretion ant's burden of proving, as bearing on right to their trade name for chloroquine phosphate, support of new drug application were insuffi- on procedural question of whether hearing is to benefit of grandfather clause exemption from when the drug was offered for use in the treat- cient and failed to demonstrate the safety of the be allowed, test is whether there is any genuine showing of effectiveness, that on October 9, 1962 ment of lupus erythematosus was question for new drug. Edison Pharmaceutical Co., Inc. V. and substantial evidence that supports position the drug was generally recognized among quali- jury in user's action against manufacturers for Food and Drug Admin., Dept. of Health, Ed. of applicant. Hynson, Westcott & Dunning, Inc. fied experts as safe for use under the conditions loss of vision as result of using the drug. Hoff- and Welfare, 1979, 600 F.2d 831, 195 U.S.App. V. Richardson, C.A.4 1972, 461 F.2d 215, modi- prescribed, recommended or suggested in the man V. Sterling Drug, Inc., C.A.Pa.1973, 485 D.C. 17. fied on other grounds 93 S.Ct. 2469, 412 U.S. labeling as of that date. U.S. V. 1,048,000 Cap- F.2d 132, on remand 374 F.Supp. 850. A drug can be generally recognized as effec- 609, 37 L.Ed.2d 207. sules, More or Less, D.C.Tex.1972, 847 F.Supp. Whether manufacturers' alleged violation of tive only if the expert consensus is based upon Evidence in proceeding to withdraw approval 768, affirmed 494 F.2d 1158. this section in the introduction of "Aralen" (chlo- substantial evidence that the drug is effective of drug supported finding that manufacturer's 22a. Admissibility of evidence roquine phosphate) without new drug statement for the labeled use; anecdotal evidence, such as studies of effect of drug, which was designed to for use in the treatment of lupus erythematosus testimonials by satisfied patients or statements reduce incidence of certain attacks of vertigo, At hearing on new drug application, adminis- was proximate cause of the user's loss of vision by doctors that, based on their experience, they were not sufficiently adequate and well con- trative law judge properly excluded testimonial from use of the drug was question for the jury. believe the drug is effective do not constitute trolled as to constitute substantial evidence of evidence which the drug manufacturer offered to Hoffman V. Sterling Drug, Inc., C.A.Pa.1973, 485 adequate and well-controlled investigations and claims for efficacy. Unimed, Inc. V. Richardson, demonstrate the efficacy of the new drug; per- F.2d 132, on remand 374 Supp. 850. cannot provide substantial evidence of effective- 1972, 458 F.2d 787, 147 U.S.App.D.C. 368. sonal testimonials simply did not meet the exact- ness. Simeon Management Corp. V. F.T.C., ing standard of evidence required by this chap- 25. Injunction C.A.9, 1978, 579 F.2d 1187. Substantial evidence of safety and effective- ter and regulations. Edison Pharmaceutical ness of alleged new drug can be shown only by Corporation which acquired title to new drug Co., Inc. V. Food and Drug Admin., Dept. of application was not in contempt of order enjoin- 218 910 21 8 355 FOOD AND DRUGS Note 25 ing previous holder of application from infring- FOOD AND DRUGS 21 § 355 ing plaintiff's drug patents; plaintiff failed to antibiotic drug. manufacturer was not entitled to show that corporation, which acquired title to preliminary injunction to compel Food and Drug Note 27 application and which was not a party to patent Administration to withhold approval of competi- Administration developed proper administrative Pharmaceutical Manufacturers V. Department of tor's application to market generic version of record to support its claim that laetrile was a infringement case, was an instrumentality of Health and Human Services, D.C.N.Y.1984, 586 manufacturer's new antibiotic drug; public in- new drug. Rutherford V. U.S., D.C.Okl.1977, F.Supp. 740. previous holder designed to evade injunction or acted in concert or in participation with original terest was best served by allowing agency to 429 F.Supp. 506. Record was inadequate to support finding that defendants in patent infringement action, and interpret its own regulations and to operate In cancer patient's action for preliminary in- Food and Drug Administration abused its dis- new drug application was not equivalent to prod- unimpeded by courts in such matter. Glaxo, junction to restrain government or its agents cretion by failing to exercise authority to imme- uct addressed and did not authorize anyone to Inc. V. Heckler, D.C.N.C.1985, 623 F.Supp. 69. from barring patient's importation of Laetrile diately suspend drugs which present an immi- make, use or sell drug. EH Lilly and Co. V. Even if placement of an over-the-counter drug solely for his personal use, plaintiff failed to nent hazard to the public health. American Premo Pharmaceutical Laboratories, Inc., in Category III, absent grandfather status or demonstrate substantial probability of success Public Health Ass'n. V. Veneman, D.C.D.C.1972, C.A.Fed. (N.J.) 1988, 843 F.2d 1378. coverage by a new drug application, was tanta- with respect to his claim that Laetrile was not 349 F.Supp. 1311. Where court's recall order did not address mount to a finding of illegality under this chap- "new drug" within meaning of this section pro- ter, it was not necessary to issue an injunction hibiting importation of such drug until approval 27. Summary judgment particular violation of this chapter from which injury might be presumed, an independent requiring the commissioner to take the drugs off of new drug application by Food and Drug Study which compared new drug's efficacy showing of irreparable harm was required to the over-the-counter market, but only necessary Administration. Gadler V. U.S., D.C.Minn.1977, against that of drug known to be effective and to issue an injunction prohibiting the commis- 425 F.Supp. 244. which observed that rate of remission for known warrant issuance of such order. U.S. V. Spectro Foods Corp., C.A.N.J.1976, 544 F.2d 1175. sioner from implementing the offensive aspects Proper procedure for manufacturers and dis- drug was 56.5% and that for new drug was of the subject regulations. Cutler V. Kennedy, Questions as to whether laetrile was marketed tributors of prescription drug involved in pro- 27.6% and thus did not show new drug to be as D.C.D.C.1979, 475 F.Supp. 838. on October 9, 1962, as a cancer drug and was ceeding to withdraw approval of new drug appli- effective as active control did not produce evi- then generally recognized as safe, or whether it Litigation by Food and Drug Administration cations was to raise defense of res judicata in dence of new drug's efficacy and thus did not was recognized or used as a cancer drug under of new drug status of two products manufac- the administrative proceedings and then have meet Food and Drug Administration's regulato- the same conditions of present use during the tured by plaintiff in pending condemnation ac- the agency determination on that issue, should it ry standards for adequate and well-controlled period when the Food and Drugs Act of 1906 tions would not be preliminarily enjoined given be contrary to their claim, reviewed on appeal to investigations 80 as to preclude summary judg- [Act June 30, 1906, Ch. 8915, 84 Stat. 768] was in serious question as to correctness of dictum in court of appeals from whatever adverse final ment order denying new drug application. Hol- effect, and thus question of whether laetrile is Lannett decision permitting a generic or "me- decision the FDA might make with respect to land-Rantos Co., Inc. V. U.S. Dept. of Health, exempt as a new drug under this section were too" drug to be marketed without premarketing withdrawal proceedings and manufacturers and Ed. and Welfare, 1978, 587 F.2d 1173, 190 U.S.App.D.C. 276. sufficiently substantial, difficult and doubtful to approval if its therapeutically active ingredients distributors were not entitled to circumvent the support grant of preliminary injunction against are identical to a recognized drug both chemical- administrative channels by seeking to enjoin the Food and Drug Administration's endorsement interference with cancer patient's personal use ly and quantitatively. Pharmadyne Laborato- proceeding. Sterling Drug, Inc. V. Weinberger, of Dexedrine as effective for short term manage- of the drug. Rutherford V. U.S., C.A.OkL1976, ries, Inc. V. Kennedy, D.C.N.J.1979, 466 F.Supp. D.C.N.Y.1974, 384 F.Supp. 557, affirmed 509 ment of obesity provided prima facie support for 100, affirmed 596 F.2d 568. 542 F.2d 1137, on remand 424 F.Supp. 105. F.2d 1236. drug manufacturer's use of Dexedrine as active District court did not abuse its discretion in Plaintiff who was dying from cancer of the control in testing efficacy of new drug to be used 26. Record pancreas and who sought to enjoin the Food and in the control of obesity, precluding summary refusing to enjoin United States authorities from interfering with distribution of specified vitamin Drug Administration from interfering with im- Food and Drug Administration must produce judgment order denying new drug application on portation or interstate transportation of Laetrile an administrative record to support its determi- ground that clinical trials testing drug's efficacy which had not been approved for distribution by for purposes of his own consumption raised right nation that laetrile is a new drug; FDA must were deficient under FDA regulation requiring the Food and Drug Administration, in absence of privacy issue sufficiently serious to be fair present substantial evidence to support the that study provide comparison of results of of showing by distributors that there was sub- grounds for litigation, warranting preliminary proposition that laetrile is not generally recog- treatment or diagnosis with a control in such a stantial probability of success with respect to their claim that such vitamin was not a sub- injunction. Rizzo V. U.S., D.C.N.Y.1977, 432 nized among qualified experts as safe and effec- fashion as to permit quantitative evaluation. F.Supp. 356. tive and that its use is not grandfathered in. Smithkline Corp. V. Food and Drug Administra- stance subject to control within meaning of this Plaintiff who was dying from cancer and who Rutherford V. U.S., C.A.Okl.1976, 542 F.2d 1137, tion, 1978, 587 F.2d 1107, 190 U.S.App.D.C. 210. chapter. Hanson V. U.S., C.A.Minn.1976, 540 F.2d 947. sought to enjoin Food and Drug Administration on remand 424 F.Supp. 105. This section granting applicant's right to due Pharmaceutical company was not entitled to from preventing importation or interstate trans- Record established that studies whereby 50 notice and opportunity for hearing prior to with- portation of Laetrile for purposes of his own patients with herpes zoster were treated with drawal of approval to market new drugs in injunctive relief prohibiting Food and Drug Ad- consumption raised due process question in re- drug while six received a placebo but without interstate commerce does not preclude use of ministration from granting approval of generic gard to requirement of filing and prosecution of method of selecting patients to insure that sub- summary judgment procedure by Food and copies of drug product Desyrel, trazadone HCL within ten-year period of nonpatent marketing a "new drug" application of sufficient serious- jects were suitable for purposes of study, with- Drug Administration in appropriate circum- exclusivity provided by 1984 amendments to the ness to make it fair grounds for litigation, war- out subjects being designed in such way as to stances, but it does restrict application of that Federal Food, Drug, and Cosmetic Act; there ranting preliminary injunction. Rizzo V. U.S., minimize bias, and without comparability of per- procedure to cases in which no material factual D.C.N.Y.1977, 432 F.Supp. 356. tinent variables being assured, and study where- issue is presented and a hearing would be a was no substantial likelihood that pharmaceuti- cal company could demonstrate that letter of Balance of equities tipped decidedly in favor by 34 patients with herpes zoster were treated hollow formality. USV Pharmaceutical Corp. V. December 24, 1981, which stated that drug "is of granting temporary injunction to plaintiff, a with drug and ten with injections of Vitamin B₁₂ Secretary of Health, Ed. and Welfare, 1972, 466 approved" and which approval would except cancer patient, who sought to enjoin Food and were not "well-controlled" and were properly F.2d 455, 151 U.S.App.D.C. 284. drug from ten-year period of nonpatent market- Drug Administration from preventing importa- rejected by Food and Drug Administration as Manufacturer of hemorrhoidal suppositories ing exclusivity, was not approval letter, pharma- tion or interstate transportation of Laetrile for proof of efficacy of drug. Cooper Laboratories, with hydrocortisone acetate was not entitled to ceutical company did not demonstrate existence purposes of his own consumption and plaintiff Inc. V. Commissioner, Federal Food and Drug discovery of specific instances in which Food of imminent injury in connection with disclosure sufficiently demonstrated possibility of irrepara- Administration, 1974, 501 F.2d 772, 168 and Drug Administration approved drug based of safety and effectiveness data, and pharmaceu- ble injury by death. Rizzo V. U.S., D.C.N.Y. U.S.App.D.C. 212. on extrapolation, in that studies of approved tical company failed to demonstrate that grant- 1977, 432 F.Supp. 356. Exclusion from administrative record of docu- drug could not be extrapolated to newly market- ing of injunctive relief would not significantly Since plaintiff class, all terminally ill cancer ments generated in course of Food and Drug ed product simply on basis that new product harm other interested parties. Mead Johnson patients, was in danger of suffering irreparable Administration's compliance and enforcement contained same active ingredient as approved Pharmaceutical Group V. Bowen, D.D.C.1986, injury if relief in form of allowing such patients activities did not preclude meaningful public drug. U.S. V. Undetermined Quantities of an 655 F.Supp. 53, affirmed 838 F.2d. 1332, 267 who wished to import laetrile for use was post- comment on or judicial review of Administra- Article of Drug (Anucort HC Suppositories), U.S.App.D.C. 382. poned or denied and the potential loss to the tion's "current good manufacturing practice" D.N.J.1987, 709 F.Supp. 511, affirmed 857 F.2d Absent showing that probable injury to drug Food and Drug Administration from granting of regulations in view of their general, nontechnical 1464, 1466, certiorari denied 109 S.Ct. 864, 488 nanufacturer without preliminary injunction relief was slight and record disclosed indications nature, especially as administrative record did U.S. 1040, 102 L.Ed.2d 988. outweighed harm to Food and Drug Administra- that laetrile was exempt from new drug classifi- include descriptive summaries of the Adminis- In action brought against Secretary by physi- ion and competitor with preliminary injunction cation under grandfather clause, court would tration's enforcement activities and most of the cians and patients who sought to preliminarily or showing of likelihood of success on merits, grant temporary injunction to permit class to actual documents were available for public in- enjoin Secretary from implementing order sus- import and use laetrile while the Food and Drug spection either in the Administration's files or pending new drug applications for phenformin 220 through requests under Freedom of Information hydrochloride on ground that drug posed an Act 559 5 21 § 355 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 Note 27 Note 33 Secretary was precluded by existence of issues of material fact. Forsham V. Califano, D.C.D.C. muco-evacuant drug "Alevaire," the court of ap- made and it became clear on what specific infor- trative determination, the district court, in exer- peals would deny manufacturers' motion to re- mation FDA relied for its conclusion, could court 1977, 442 F.Supp. 208. cise of its sound discretion under Declaratory quire the Administration to remove a listing of determine whether data used constituted new Judgment Act, section 2201 et seq. of Title 28, 28. Review "Alevaire" as "ineffective" from the Administra- information. Sterling Drug, Inc. V. Weinberger, would refuse to take jurisdiction of action for While a Food and Drug Administration order tion's Interim Index. Sterling Drug Inc. V. D.C.N.Y.1974, 884 F.Supp. 557, affirmed 509 declaration that particular drugs were not "new denying a new drug application or withdrawing Weinberger, C.A.2, 1974, 508 F2d 675. F.2d 1236. drug." National Ethical Pharmaceutical Ass'n one is reviewable by the Court of Appeals under Issue of whether anorectic drugs containing Complaint seeking determination as to wheth- V. Weinberger, D.C.S.C.1978, 365 F.Supp. 785, this section, an order declaring a "new drug" amphetamines were "grandfathered" by 1962 er drug was 8 "new drug" was an inappropriate affirmed 503 F.2d 1051. status is reviewable under the Administrative amendments to this chapter was initially a mat- vehicle to determine issues of case as, if plain- ter for determination of the Food and Drug 30. Prescription drugs Procedure Act, sections 551 et seq. and 701 et tiffs were to seek judicial review of any Food seq. of Title 5, by the district court. Wein- Administration, subject to review in district and Drug Administration order, complaint would Prescription drugs on market are subject to berger V. Bentex Pharmaceuticals, Inc., S.C. court pursuant to the Administrative Procedure have to be withdrawn and petition for review efficacy requirements of this chapter. USV 1978, 98 S.Ct. 2488, 412 U.S. 645, 87 L.Ed.2d Act, sections 551 et seq. and 701 et seq. of Title substituted. Carolina Brown, Inc. V. Wein- Pharmaceutical Corp. V. Weinberger, Va.1973, 285. 5, and could not be determined by the Court of berger, D.C.S.C.1973, 365 F.Supp. 310. 93 S.Ct. 2498, 412 U.S. 640, 37 L.Ed.2d 230. Declaratory order of Food and Drug Adminis- Appeals in action by manufacturers of such Manufacturer of pioneer antibiotic drug was drugs to set aside order of Administration with- 28a. Standards of review tration that a drug is a "new drug" so as to not entitled to protection of amendment to Fed- require an effective new drug application before drawing approval of new-drug applications cov- The Food and Drug Administration's denial of eral Food, Drug and Cosmetic Act preventing drug may be introduced into commerce is not ering combination amphetamine products. claimant's request for relabeling of medical de- any manufacturer of prescription pharmaceutical reviewable in the Court of Appeals under sub- North American Pharmacal, Inc. V. Department vice was an informal adjudicatory process, as to drugs from marketing generic version of drug sec, (h) of this section, but is reviewable by the of Health, Ed. and Welfare, C.A.8, 1973, 491 which Administration was not required to con- for five years from date of pioneer drug's ap- F.2d 546. district court under Administrative Procedure duct an "on the record" hearing to produce proval, where drug had not been submitted and Act, sections 551 et seq. and 701 et seq. of Title Court of Appeals did not lack jurisdiction to record that was basis of action, the basic re- approved pursuant to referenced section and 5. Weinberger V. Hynson, Westcott and Dun- review merits of petition by manufacturers of quirement for substantial evidence review, and had been approved pursuant to another section ning, Inc., Va.1978, 98 S.Ct. 2469, 412 U.S. 609, anorectic drugs containing amphetamines to set thus, decision to deny relabeling was subject to and only thereafter exempted and subsequently 37 L.Ed.2d 285. aside order of Food and Drug Administration review under the arbitrary and capricious stan- regulated under governing statute. Glaxo, Inc. In reviewing an order of the Commissioner withdrawing approval of new-drug applications dard contained in 5 U.S.C.A. $ 706(2)(A). U.S. V. Bowen, E.D.N.C.1986, 640 F.Supp. 933. denying a hearing on proposed withdrawal of an covering combination amphetamine products be- V. An Article of Device Diapulse, C.A.7 (III) effective new drug application because of lack of cause manufacturers were not holders of such 1985, 768 F.2d 826. 31. Drugs administered by physicians substantial evidence of efficacy of the drug, a applications but manufactured drugs which were Whether or not endocrine drug was a "new Court of Appeals must determine whether the identical, similar or related to drugs covered by 29. Declaratory judgment drug," operators of weight reduction clinics were Commissioner's findings accurately reflect study: another manufacturer's new drug application. Where order of Commissioner on Food and not required to seek Food and Drug Administra- in question and if they do, whether the deficien- North American Pharmacal, Inc. V. Department Drugs withdrawing drug manufacturer's new tion approval for use of the drug in treatments cies he finds conclusively render the study inad- of Health, Ed. and Welfare, C.A.8, 1978, 491 drug applications had not become final prior to administered by licensed physicians. F.T.C. V. F.2d 546. equate or uncontrolled in light of the pertinent district court assuming jurisdiction of manufac- Simeon Management Corp., D.C.Cal.1975, 391 regulations. Weinberger V. Hynson, Westcott In suit for damages and injunctive relief based turer's suit for declaratory judgment that its F.Supp. 697, affirmed 582 F.2d 708. and Dunning, Inc., Va.1973, 93 S.Ct. 2469, 412 on alleged conspiracy by defendants to keep drugs were exempt from efficacy requirements, The Food and Drug Administration does not U.S. 609, 37 L.Ed.2d 235. plaintiffs' drug off interstate market by influenc- and in fact the Court of Appeals had reversed have jurisdiction to regulate the administration Deference owed to political branches in mill- ing the Administration to deny fair consideration the Commissioner's decision and proceedings on of a drug by a physician. F.T.C. V. Simeon tary matters did not preclude judicial review of of new drug applications, district court should remand were pending before the Commission, Management Corp., D.C.Cal.1975, 391 F.Supp. Food and Drug Administration (FDA) regula- not be inhibited from considering conclusions manufacturer was not barred from proceeding in 697, affirmed 532 F2d 708. tion permitting Defense Department to use reached by the Administration with respect to the district court. USV Pharmaceutical Corp. V. unapproved, investigational drugs on military safety and efficacy of drug for interstate sale in Weinberger, Va.1978, 93 S.Ct. 2498, 412 U.S. 32. Notes of approval personnel, without service member's informed light of whatever showing plaintiffs make of the 640, 37 L.Ed.2d 230. Where Food and Drug Administration had consent, in certain combat-related situations. existence of a conspiracy, unfairness, or conflict Drug manufacturer, who had opportunity to issued and published in the Federal Register a Doe V. Sullivan, C.A.D.C.1991, 938 F.2d 1870. of interests on part of defendants. Israel V. litigate jurisdictional question whether drug new "Notice of Opportunity for Hearing" on Baxter Laboratories, Inc., 1972, 466 F.2d 272, product was a "new drug" before Food and proposal withdrawing approval of New Drug District court could not reconsider the issue of 151 U.S.App.D.C. 101. drug's lack of effectiveness for alleviation of Drug Administration and to raise issue on ap- Applications for "Alevaire," a muco-evacuant pain, and had no jurisdiction to reopen the case, District court's review of decision of Secretary peal to a court of appeals to review withdrawal drug, and the notice made specific reference to to suspend phenformin hydrochloride as an im- where Court of Appeals had previously affirmed order, could not relitigate the issue in a separate Court of Appeals decision which permitted the minently hazardous drug was limited to determi- district court's affirmance of finding by the Food proceeding for a declaratory judgment. CIBA notice, the Administration would not be required nation of whether Secretary's decision was arbi- Corp. V. Weinberger, N.J.1978, 93 S.Ct. 2495, to publish notice of reinstatement of approval of and Drug Administration with respect to the drug's lack of effectiveness. Rutherford V. U.S., trary and capricious, an abuse of discretion, or 412 U.S. 640, 37 L.Ed.2d 230. the new drug applications in the Federal Regis- C.A.10 (Okl.) 1986, 806 F.2d 1455. otherwise not in accordance with the law. Fors- Plaintiffs who were in commercial business of ter. Sterling Drug Inc. V. Weinberger, C.A.2, ham V. Califano, D.C.D.C.1977, 442 F.Supp. 203. 1974, 503 F.2d 675. Action of Food and Drug Administration in selling laetrile, who did not need drug, and who withdrawing new drug application for muco-eva- Any error made by Food and Drug Adminis- did not allege that they were unable to afford 32a. Opinion letters cuant "Alevaire" on ground that it was not effec- tration in its consideration of a new drug appli- new drug application procedures, were not enti- tive as a "fixed combination drug" was arbitrary cation or an abbreviated new drug application tled to relief in their action for declaratory Issuance of opinion letter stating that particu- and invalid where there was no mention of that for drug X-Otag Plus manufactured by defen- judgment that laetrile is a food and is not a new lar drug product would not require clearance dant was not for consideration of district court under "new drug" procedure was beyond statu- theory as ground for proposed withdrawal in the drug and for order decreeing that no agency of in enforcement proceeding brought by United notice of opportunity for hearing and the manu- United States has right to interfere with impor- tory authority of Food and Drug Administration, States, but was for consideration of court of tation and distribution of laetrile on theory that which had no legal authority to permit market- facturers were never given a meaningful oppor- appeals after a final agency determination on ing of the product without new drug application tunity to submit studies or data to contravene it is unconstitutional to deny consumer of lae- status of drug. U.S. V. X-Otag Plus Tablets, approved for safety and efficacy. U.S. V. Arti- that theory. Sterling Drug Inc. V. Weinberger, trile opportunity to obtain it because consumer D.C.Colo.1977, 441 F.Supp. 105, affirmed in cles of Drug HORMONIN, D.C.N.J.1980, C.A.2, 1974, 503 F.2d 675. cannot afford costly procedures required for part, remanded in part on other grounds 602 new drug application. Hanson V. U.S., 498 F.Supp. 424, affirmed 672 F.2d 902, 904. Where the nature of the Food and Drug F.2d 1387. D.C.Minn.1976, 417 F.Supp. 30, affirmed 540 33. Remedy Administration Interim Index and the basis on Whether FDA had "new information" justify- F.2d 947. which listings thereon are made were not before This section which provides that court may the court of appeals and were not explored on ing withdrawal of approval of new drug applica- Where issue of whether drug is "new drug" order additional evidence to be taken and to be appeal from Administration's orders which with- tion in effect for prescription drug was factual was matter within the primary jurisdiction of adduced upon hearing in such manner and upon drew approval of new drug applications for determination which should first be made by the Food and Drug Administration and judicial such terms as to court may seem proper and FDA and, only after that determination was review would be available following the adminis- that Commissioner may modify findings as to 222 000 21 § 355 FOOD AND DRUGS Note 33 FOOD AND DRUGS 21 § 357 facts by reason of additional evidence gives If Food and Drug Administration has not court broad authority to fashion a remedy capa- developed adequate administrative record to 1 and Pub.L. 96-88 and Pub.L. 102-300, the 96-88, Title VI, Oct. 17, 1979, 93 Stat. 696, set ble of balancing fairness to new drug applicant permit determination whether laetrile is proper- amendment resulted in no change in text. out as a note under section 3401 of Title 20, against public's right to expeditious enforcement of this chapter. Smithkline Corp V. Food and ly classified as a new drug, appropriate proce- 1992 Amendments Education, deemed to refer and apply to the dure for district court is to remand the case to Department of Health and Human Services or Drug Administration, 1978, 587 F.2d 1107, 190 the FDA for proceedings adequate to develop Subsec. (a). Pub.L. 102-300, $ 6(b)(2), struck the Secretary of Health and Human Services, U.S.App.D.C. 210. the record; such proceedings should give lae- out "of Health, Education, and Welfare" follow- respectively, except to the extent such reference trile proponents an opportunity to express their ing "The Secretary". Creation of federal common-law damages is to a function or office transferred to the remedy under this chapter was not necessary to views. Rutherford V. U.S., C.A.Okl.1976, 542 Change of Name Secretary of Education or the Department of enforcement of claims asserted in individual's F.2d 1187, on remand 424 F.Supp. 105. The Department of Health, Education, and Education under Pub.L. 96-88, Title III, §§ 301 suit against drug companies to recover damages 35. Investigatory drugs Welfare was redesignated the Department of to 307, Oct. 17, 1979, 93 Stat. 677 to 681. See arising out of purchase of allegedly ineffective section 3441 to 3447 and 8508 of Title 20. drugs, since cause of action in question was of Food and Drug Administration (FDA) had Health and Human Services, and the Secretary kind traditionally governed by state law. Con- authority, under statute regulating new drug of Health, Education, and Welfare or any other investigations, to impose recordkeeping require- official of the Department of Health, Education Federal Policy Regarding the Export of sumer Federation of America V. Upjohn Co., and Welfare was redesignated the Secretary or Banned or Significantly Restricted Sub- D.C.App.1975, 846 A.2d 725. ments on clinical investigators of new drugs, in light of dangers incumbent in receipt of false official, as appropriate, of Health and Human stances data. U.S. V. Garfinkel, C.A.8 (Minn.) 1994, 29 Services, with any reference to the Department For provisions relating to the applicability of 34. Remand F.8d 451. of Health, Education, and Welfare, the Secre- the term "banned or significantly restricted sub- Where trial before district court should not Food and Drug Administration (FDA) regula- tary of Health, Education, and Welfare, or any stance", as defined, and the Federal policy re- have occurred, and its record was part of admin- tion permitting Defense Department to use official of the Department of Health, Education, garding the export of banned or significantly istrative record on remand solely for information unapproved, investigational drugs on military and Welfare, in any law, rule, regulation, certifi- restricted substances, see section 1-101 of Ex. it contained and as a matter of administrative personnel, without service member's informed cate, directive, instruction, or other official pa- Ord. No. 12264, Jan. 15, 1981, 46 F.R. 4659, set convenience, the Food and Drug Administration, consent, in certain combat-related situations, per in force on the effective date of Pub.L. out as a note under section 2403 of Title 50, in proceeding on claimant's request for relabel- was within FDA's rule-making authority under 96-88, as prescribed by section 601 of Pub.L. Appendix, War and National Defense. ing of medical devices, was not bound by find- Food, Drug, and Cosmetic Act, which provided ings of the district court, and fact that trial for use of unimproved investigational drugs only CODE OF FEDERAL REGULATIONS procedure took place did not transform the Ad- on the informed consent of human subjects af- Drugs composed wholly or partly of insulin, ministration's decision-making process into adju- fected "except where [the experts administering see 21 CFR 429.3. dicatory hearing. U.S. V. An Article of Device the drug] deem [the human subject's consent] Diapulse, C.A.7 (III.) 1985, 768 F.2d 826. not feasible." Doe V. Sullivan, C.A.D.C.1991, 988 F.2d 1370. § 357. Certification of drugs containing penicillin, streptomycin, chlortetracy- There was no error in refusing to remand to cline, chloramphenicol, bacitracin or any other antibiotic drug the Food and Drug Administration for develop- 36. Labeling information ment of an administrative record in support of Plaintiffs could not recover from name brand (a) Regulations prescribed by Secretary; release prior to certification; "antibiotic Food and Drug Administration's contention that manufacturer for death of their daughter who drug" defined drug was a new drug requiring approval of a new drug application, where the Administration died as result of ingesting generic equivalent of The Secretary, pursuant to regulations promulgated by him, shall provide for the had only instituted condemnation proceedings drug on theory that negligent misrepresenta- tions on generic drug's label were merely copied, certification of batches of drugs (except drugs for use in animals other than man) against a certain quantity of the drug and in- as permitted by federal law, from name brand composed wholly or partly of any kind of penicillin, streptomycin, chlortetracycline, junction proceedings against a single drug man- ufacturer, 80 that its action was not in the manufacturer's label; manufacturer of generic chloramphenicol, bacitracin, or any other antibiotic drug, or any derivative thereof. A drug was responsible for accuracy of labels batch of any such drug shall be certified if such drug has such characteristics of identity nature of a declaratory order, and where deter- placed on its products and name brand manufac- and such batch has such characteristics of strength, quality, and purity, as the Secretary mination that the drug was a "new drug" for turer's statements regarding its drug could not purposes of condemnation and injunction pro- prescribes in such regulations as necessary to adequately insure safety and efficacy of ceedings was made by the district court follow- serve as basis for liability for injuries caused by use, but shall not otherwise be certified. Prior to the effective date of such regulations ing trial. U.S. V. X-Otag Plus Tablets, another manufacturer's drug. Foster V. Ameri- the Secretary, in lieu of certification, shall issue a release for any batch which, in his C.A.Colo.1979, 602 F.2d 1387. can Home Products Corp., C.A.4 (Md.) 1994, 29 F.3d 165. judgment, may be released without risk as to the safety and efficacy of its use. Such release shall prescribe the date of its expiration and other conditions under which it shall § 356. Certification of drugs containing insulin cease to be effective as to such batch and as to portions thereof. For purposes of this section and of section 352(I) of this title, the term "antibiotic drug" means any drug (a) The Secretary, pursuant to regulations promulgated by him, shall provide for the intended for use by man containing any quantity of any chemical substance which is certification of batches of drugs composed wholly or partly of insulin. A batch of any produced by a microorganism and which has the capacity to inhibit or destroy microor- such drug shall be certified if such drug has such characteristics of identity and such ganisms in dilute solution (including the chemically synthesized equivalent of any such batch has such characteristics of strength, quality, and purity, as the Secretary substance). prescribes in such regulations as necessary to adequately insure safety and efficacy of use, but shall not otherwise be certified. Prior to the effective date of such regulations [See main volume for text of (b) to (d)] the Secretary, in lieu of certification, shall issue a release for any batch which, in his judgment, may be released without risk as to the safety and efficacy of its use. Such (e) Exempted new drugs subject to section 355 of this title; request for certifica- release shall prescribe the date of its expiration and other conditions under which it shall tion of exempted drug; determination of compliance with sections 351(b) and 352(g) of this title cease to be effective as to such batch and as to portions thereof. No drug which is subject to this section shall be deemed to be subject to any provision [See main volume for text of (b) and (c)] of section 355 of this title except a new drug exempted from the requirements of this (As amended June 16, 1992, Pub.L. 102-300, $ 6(b)(2), 106 Stat. 240; Aug. 13, 1993, Pub.L. 103-80, section and of section 352(I) of this title pursuant to regulations promulgated by the $ 3(o), 107 Stat. 777.) Secretary. For purposes of section 355 of this title, the initial request for certification, as thereafter duly amended, pursuant to this section, of a new drug so exempted shall be HISTORICAL AND STATUTORY NOTES considered a part of the application filed pursuant to section 355(b) of this title with Ch. 13 Ch. 13 DRUG ABUSE PREVENTION AND CONTROL 21 § 811 ), 84 Stat. 1242, and is popularly 960 and 961 of this title] shall take effect 120 days after the § 803. Repealed. Pub.L. 95-137, § 1(b), Oct. 18, Substances Act". For complete enactment of this Act [Nov. 18, 1988]." 1977, 91 Stat. 1169. e Code, see Short Title note set Change of Name. "Secretary of Health and Human this title and Tables volume. Services" was substituted for "Secretary of Health, Edu- PART B-AUTHORITY TO CONTROL: STANDARDS AND SCHEDULES pter", referred to in text, was in cation, and Welfare" on authority of Pub.L. 96-88, Title V, ning Title III of Pub.L. 91-513, § 509, Oct. 17, 1979, 93 Stat. 695, which is classified to § 811. Authority and criteria for classification Part A of Title III comprises section 3508 of Title 20, U.S.C.A., Education. of substances '1'. For classification of Part B, Regulations by Attorney General. Section 1903 of Rules and regulations of Attorney to 1105 of Title III, see Tables Pub.L. 101-647 provided that: General; hearing "(a) Abuse potential.-The Attorney General, upon the and Cosmetic Act, referred to in recommendation of the Secretary of Health and Human (a) The Attorney General shall apply the provi- 25, 1938, c. 675, 52 Stat. 1040, as Services, may, by regulation, exempt any compound, mix- sions of this subchapter to the controlled substances generally to chapter 9 (§ 301 et ture, or preparation containing a substance in paragraph listed in the schedules established by section 812 of olete classification of this Act to (41) of section 102 of the Controlled Substances Act [par. this title and to any other drug or other substance of this title and Tables volume. (41) of this section] (as added by section 2 of this Act [sic]) added to such schedules under this subchapter. Ex- Revenue Code of 1986, referred from the application of all or any part of the Controlled cept as provided in subsections (d) and (e) of this section 5001 et seq. of Title 26, Substances Act [21 U.S.C.A. § 801 et seq.] if, because of its section, the Attorney General may by rule- Code. concentration, preparation, mixture or delivery system, it has no significant potential for abuse. (1) add to such a schedule or transfer between to in par. (32)(A), are set out in such schedules any drug or other substance if he- "(b) Drugs for treatment of rare diseases.-If the At- torney General finds that a drug listed in paragraph (41) of (A) finds that such drug or other substance ent by section 83 of Pub.L. section 102 of the Controlled Substances Act (as added by has a potential for abuse, and not executed in view of prior section 2 of this Act [sic]) is- (B) makes with respect to such drug or other Pub.L. 99-570 making identical "(1) approved by the Food and Drug Administration as substance the findings prescribed by subsection an accepted treatment for a rare disease or condition, as (b) of section 812 of this title for the schedule in 1954 in any law, etc., to include defined in section 526 of the Federal Food, Drug, and which such drug is to be placed; or nue Code of 1986, except when Cosmetic Act (21 U.S.C. 360bb) [21 U.S.C.A. $ 360bb]; (2) remove any drug or other substance from the 9-514, § 2, Oct. 22, 1986, 100 and schedules if he finds that the drug or other sub- "(2) does not have a significant potential for abuse, the stance does not meet the requirements for inclu- )1(a) of Pub.L. 98-509, Oct. 19, Attorney General may exempt such drug from any pro- sion in any schedule. .r. (28) which substituted "one duction regulations otherwise issued under the Controlled venty-one" was executed to par. Rules of the Attorney General under this subsection Substances Act [21 U.S.C.A. $ 801 et seq.] as may be '8) prior to its redesignation by necessary to ensure adequate supplies of such drug for shall be made on the record after opportunity for a 507(a), Oct. 12, 1984, 98 Stat. medical purposes. hearing pursuant to the rulemaking procedures pre- of Congress. scribed by subchapter II of chapter 5 of Title 5. "(c) Date of issuance of regulations.-The Attorney mendments. Section 330024(f) General shall issue regulations implementing this section not Proceedings for the issuance, amendment, or repeal that: "The amendments made later than 45 days after the date of enactment of this Act of such rules may be initiated by the Attorney Gener- is section and sections 824, 960, [Nov. 29, 1990], except that the regulations required under al (1) on his own motion, (2) at the request of the ake effect as of the date that is section 3(a) [sic] shall be issued not later than 180 days after Secretary, or (3) on the petition of any interested of enactment of the Domestic the date of enactment of this Act [Nov. 29, 1990]." party. I Act of 1993 [Dec. 17, 1993]. Promulgation of Regulations for Administration of Amendments. Section 11 of Evaluation of drugs and other substances Amendment by Alcohol Abuse, Drug Abuse, and Mental at: "This Act and the amend- Health Amendments of 1984; Inclusion of Findings in (b) The Attorney General shall, before initiating nacting section 814 of this title, Report. Section 301(b) of Pub.L. 98-509, Oct. 19, 1984, 98 proceedings under subsection (a) of this section to sections 821, 822, 823, 824, 830, Stat. 2364, provided that: "The Secretary of Health and control a drug or other substance or to remove a I 971 of this title and enacting Human Services shall, within ninety days of the date of the drug or other substance entirely from the schedules, under this section and section enactment of this Act [Oct. 19, 1984], promulgate regulations and after gathering the necessary data, request from fect on the date that is 120 days for the administration of section 102(28) of the Controlled it of this Act [Dec. 17, 1993]. the Secretary a scientific and medical evaluation, and Substances Act as amended by subsection (a) [probably par. his recommendations, as to whether such drug or mendment. Section 1902(d) 29 of this section] and shall include in the first report other substance should be so controlled or removed it: "This section and the amend- submitted under section 505(b) of the Public Health Service enacting par. (41) of this section, Act [section 290aa-4 of Title 42, The Public Health and as a controlled substance. In making such evaluation S title, and enacting a provision Welfare] after the expiration of such ninety days the find- and recommendations, the Secretary shall consider tion 829 of this title] shall ings of the Secretary with respect to the effect of the the factors listed in paragraphs (2), (3), (6), (7), and of enactment of this Act [No amendment made by subsection (a) [amending par. (29) of (8) of subsection (c) of this section and any scientific this section]." or medical considerations involved in paragraphs (1), it: Amendment. "Except as otherwise provide Section 6061 (4), and (5) of such subsection. The recommenda- Code of Federal Regulations tions of the Secretary shall include recommendations itle [enacting section 972 of Controlled drugs, warnings, see 21 CFR 290.5 et seq. with respect to the appropriate schedule, if any, 830, 841, 842, 843, 872, 876, 8814 Treatment of narcotic addicts, see 21 CFR 291.501 et seq. under which such drug or other substance should be Complete Annotation Materials, see Title 21, U.S.C.A. 1043 21 § 811 FOOD AND DRUGS Ch. 13 Ch. 13 listed. The evaluation and the recommendations of (2)(A) Whenever the Secretary of State receives drug or substance and th. the Secretary shall be made in writing and submitted notification from the Secretary-General of the United Federal Food, Drug, and to the Attorney General within a reasonable time. Nations that information has been transmitted by or requirements of the sched\ The recommendations of the Secretary to the Attor- to the World Health Organization, pursuant to article tion or schedule notice at ney General shall be binding on the Attorney General 2 of the Convention on Psychotropic Substances, action: as to such scientific and medical matters, and if the which may justify adding a drug or other substance (A) If such requireme Secretary recommends that a drug or other sub- to one of the schedules of the Convention, transfer- ing controls but the Se stance not be controlled, the Attorney General shall ring a drug or substance from one schedule to anoth- man Services nonethele not control the drug or other substance. If the er, or deleting it from the schedules, the Secretary of gent controls should t Attorney General determines that these facts and all State shall immediately transmit the notice to the substance, the Secretar other relevant data constitute substantial evidence of Secretary of Health and Human Services who shall Attorney General that potential for abuse such as to warrant control or publish it in the Federal Register and provide oppor- scheduling the drug or substantial evidence that the drug or other substance tunity to interested persons to submit to him com- sections (a) and (b) of t should be removed entirely from the schedules, he ments respecting the scientific and medical evalua- controls. shall initiate proceedings for control or removal, as tions which he is to prepare respecting such drug or (B) If such requirer the case may be, under subsection (a) of this section. substance. The Secretary of Health and Human existing controls and t Services shall prepare for transmission through the Human Services concur Factors determinative of control Secretary of State to the World Health Organization or schedule notice trai or removal from schedules such medical and scientific evaluations as may be the Secretary shall re (c) In making any finding under subsection (a) of appropriate regarding the possible action that could General that he initiate this section or under subsection (b) of section 812 of be proposed by the World Health Organization re- the drug or substance this title, the Attorney General shall consider the specting the drug or substance with respect to which ule pursuant to subs- following factors with respect to each drug or other a notice was transmitted under this subparagraph. section. substance proposed to be controlled or removed from (B) Whenever the Secretary of State receives in- (C) If such require! the schedules: formation that the Commission on Narcotic Drugs of existing controls and 1 (1) Its actual or relative potential for abuse. the United Nations proposes to decide whether to Human Services does add a drug or other substance to one of the schedules (2) Scientific evidence of its pharmacological ef- decision or schedule no of the Convention, transfer a drug or substance from fect, if known. fication, the Secretary one schedule to another, or delete it from the sched- (3) The state of current scientific knowledge re- ules, the Secretary of State shall transmit timely (i) if he deems garding the drug or other substance. notice to the Secretary of Health and Human Ser- necessary to protect (4) Its history and current pattern of abuse. vices of such information who shall publish a sum- recommended to th (5) The scope, duration, and significance of mary of such information in the Federal Register and initiate proceedings provide opportunity to interested persons to submit substance pursuant abuse. to him comments respecting the recommendation this section, to ap! (6) What, if any, risk there is to the public which he is to furnish, pursuant to this subparagraph, (ii) request the S health. respecting such proposal. The Secretary of Health a notice of qualified and Human Services shall evaluate the proposal and specified in the C, (7) Its psychic or physiological dependence lia- furnish a recommendation to the Secretary of State graph 7 of article bility. which shall be binding on the representative of the Secretary-General (8) Whether the substance is an immediate pre- United States in discussions and negotiations relating (iii) request the cursor of a substance already controlled under this to the proposal. a notice of qualifie- subchapter. (3) When the United States receives notification of clause (ii) and requ a scheduling decision pursuant to article 2 of the ask for a review International treaties, conventions, and protocols Council of the U: requiring control; procedures respecting Convention on Psychotropic Substances that a drug changes in drug schedules of Convention on or other substance has been added or transferred to with paragraph 8 of the scheduling Psychotropic Substances a schedule specified in the notification or receives (iv) in the case (d)(1) If control is required by United States obli- notification (referred to in this subsection as a gations under international treaties, conventions, or "schedule notice") that existing legal controls applica- the Secretary of S protocols in effect on October 27, 1970, the Attorney ble under this subchapter to a drug or substance and under the Conven General shall issue an order controlling such drug the controls required by the Federal Food, Drug, and remove the drug Cosmetic Act do not meet the requirements of the ules under the ( under the schedule he deems most appropriate to schedule of the Convention in which such drug or drug or substance carry out such obligations, without regard to the substance has been placed, the Secretary of Health vention different findings required by subsection (a) of this section or section 812(b) of this title and without regard to the and Human Services, after consultation with the At- schedule notice. procedures prescribed by subsections (a) and (b) of torney General, shall first determine whether existing (4)(A) If the Attori this section. legal controls under this subchapter applicable to the consultation with the S Complete Annotation Materials, see Title 21, U.S.C.A. 1044 Ch. 13 DRUG ABUSE PREVENTION AND CONTROL 21 § 811 Ch. 13 of State receives drug or substance and the controls required by the Services, that proceedings initiated under recommen- neral of the United Federal Food, Drug, and Cosmetic Act, meet the dations made under paragraph (B) or (C)(i) of para- 1 transmitted by or requirements of the schedule specified in the notifica- graph (3) will not be completed within the time period pursuant to article tion or schedule notice and shall take the following required by paragraph 7 of article 2 of the Conven- tropic Substances, action: tion, the Attorney General, after consultation with the or other substance (A) If such requirements are met by such exist- Secretary and after providing interested persons op- onvention, transfer- ing controls but the Secretary of Health and Hu- portunity to submit comments respecting the require- schedule to anoth- man Services nonetheless believes that more strin- ments of the temporary order to be issued under this es, the Secretary of gent controls should be applied to the drug or sentence, shall issue a temporary order controlling the notice to the substance, the Secretary shall recommend to the the drug or substance under schedule IV or V, which- Services who shall Attorney General that he initiate proceedings for ever is most appropriate to carry out the minimum and provide oppor- scheduling the drug or substance, pursuant to sub- United States obligations under paragraph 7 of arti- cle 2 of the Convention. As a part of such order, the ubmit to him com- sections (a) and (b) of this section, to apply to such and medical evalua- controls. Attorney General shall, after consultation with the ecting such drug or Secretary, except such drug or substance from the (B) If such requirements are not met by such Health and Human application of any provision of part C of this subchap- existing controls and the Secretary of Health and nission through the ter which he finds is not required to carry out the Human Services concurs in the scheduling decision Health Organization United States obligations under paragraph 7 of arti- or schedule notice transmitted by the notification, uations as may be cle 2 of the Convention. In the case of proceedings the Secretary shall recommend to the Attorney le action that could initiated under subparagraph (B) of paragraph (3), General that he initiate proceedings for scheduling th Organization re- the Attorney General, concurrently with the issuance the drug or substance under the appropriate sched- ith respect to which of such order, shall request the Secretary of State to ule pursuant to subsections (a) and (b) of this this subparagraph. transmit a notice of qualified acceptance to the Secre- section. tary-General of the United Nations pursuant to para- of State receives in- (C) If such requirements are not met by such graph 7 of article 2 of the Convention. A temporary n Narcotic Drugs of existing controls and the Secretary of Health and order issued under this subparagraph controlling a decide whether to Human Services does not concur in the scheduling drug or other substance subject to proceedings initi- one of the schedules decision or schedule notice transmitted by the noti- ated under subsections (a) and (b) of this section shall g or substance from fication, the Secretary shall- e it from the sched- expire upon the effective date of the application to all transmit timely (i) if he deems that additional controls are the drug or substance of the controls resulting from th and Human Ser- necessary to protect the public health and safety, such proceedings. recommended to the Attorney General that he hall publish a sum- (B) After a notice of qualified acceptance of a 'ederal Register and initiate proceedings for scheduling the drug or scheduling decision with respect to a drug or other d persons to submit substance pursuant to subsections (a) and (b) of substance is transmitted to the Secretary-General of he recommendation this section, to apply such additional controls; the United Nations in accordance with clause (ii) or o this subparagraph, (ii) request the Secretary of State to transmit (iii) of paragraph (3)(C) or after a request has been Secretary of Health a notice of qualified acceptance, within the period made under clause (iv) of such paragraph with re- ate the proposal and specified in the Convention, pursuant to para- spect to a drug or substance described in a schedule Secretary of State graph 7 of article 2 of the Convention, to the notice, the Attorney General, after consultation with epresentative of the Secretary-General of the United Nations; the Secretary of Health and Human Services and negotiations relating (iii) request the Secretary of State to transmit after providing interested persons opportunity to sub- a notice of qualified acceptance as prescribed in mit comments respecting the requirements of the ceives notification of clause (ii) and request the Secretary of State to order to be issued under this sentence, shall issue an to article 2 of the ask for a review by the Economic and Social order controlling the drug or substance under sched- Council of the United Nations, in accordance stances that a drug ule IV or V, whichever is most appropriate to carry led or transferred to with paragraph 8 of article 2 of the Convention, out the minimum United States obligations under tification or receives of the scheduling decision; or paragraph 7 of article 2 of the Convention in the case (iv) in the case of a schedule notice, request is subsection as a of a drug or substance for which a notice of qualified egal controls applica- the Secretary of State to take appropriate action acceptance was transmitted or whichever the Attor- rug or substance and under the Convention to initiate proceedings to ney General determines is appropriate in the case of eral Food, Drug, and remove the drug or substance from the sched- a drug or substance described in a schedule notice. ules under the Convention or to transfer the requirements of the As a part of such order, the Attorney General shall, which such drug or drug or substance to a schedule under the Con- after consultation with the Secretary, except such Secretary of Health vention different from the one specified in the drug or substance from the application of any provi- ultation with the At- schedule notice. sion of part C of this subchapter which he finds is not nine whether existing (4)(A) If the Attorney General determines, after required to carry out the United States obligations pter applicable to the consultation with the Secretary of Health and Human under paragraph 7 of article 2 of the Convention. If, Complete Annotation Materials, see Title 21, U.S.C.A. 1045 FOOD AND DRUGS Ch. 13 Ch. 21 § 811 as a result of a review under paragraph 8 of article 2 Abuse potential of the Convention of the scheduling decision with (f) If, at the time a new-drug application is submit- Ge ted to the Secretary for any drug having a stimulant, int- respect to which a notice of qualified acceptance was depressant, or hallucinogenic effect on the central wh transmitted in accordance with clause (ii) or (iii) of paragraph (3)(C)- nervous system, it appears that such drug has an ( abuse potential, such information shall be forwarded ted (i) the decision is reversed, and by the Secretary to the Attorney General. (2) (ii) the drug or substance subject to such deci- Non-narcotic substances sold over the counter sectio sion is not required to be controlled under schedule without prescription; dextromethorphan date IV or V to carry out the minimum United States subst: obligations under paragraph 7 of article 2 of the (g)(1) The Attorney General shall by regulation durin; exclude any non-narcotic substance from a schedule if Convention, (a)(1) such substance may, under the Federal Food, Drug, exten- the order issued under this subparagraph with re- and Cosmetic Act, be lawfully sold over the counter mont] spect to such drug or substance shall expire upon without a prescription. (3) receipt by the United States of the review decision. (2) Dextromethorphan shall not be deemed to be the A If, as a result of action taken pursuant to action included in any schedule by reason of enactment of with I initiated under a request transmitted under clause this subchapter unless controlled after October 27, the p (iv) of paragraph (3)(C), the drug or substance with 1970 pursuant to the foregoing provisions of this parag! respect to which such action was taken is not re- section. section quired to be controlled under schedule IV or V, the (3) The Attorney General may, by regulation, ex- mate order issued under this paragraph with respect to empt any compound, mixture, or preparation contain- ture, such drug or substance shall expire upon receipt by ing a controlled substance from the application of all (4) the United States of a notice of the action taken with or any part of this subchapter if he finds such com- an orc respect to such drug or substance under the Conven- pound, mixture, or preparation meets the require- to the tion. ments of one of the following categories: issuing (C) An order issued under subparagraph (A) or (B) (A) A mixture, or preparation containing a non- Gener may be issued without regard to the findings re- narcotic controlled substance, which mixture or submit quired by subsection (a) of this section or by section preparation is approved for prescription use, and transm 812(b) of this title and without regard to the proce- which contains one or more other active ingredi- (5) dures prescribed by subsection (a) or (b) of this ents which are not listed in any schedule and which spect t are included therein in such combinations, quantity, section. sion of proportion, or concentration as to vitiate the poten- under (5) Nothing in the amendments made by the Psy- tial for abuse. such St chotropic Substances Act of 1978 or the regulations or orders promulgated thereunder shall be construed (B) A compound, mixture, or preparation which (6) to preclude requests by the Secretary of Health and contains any controlled substance, which is not for subject administration to a human being or animal, and Human Services or the Attorney General through the (Pub.L. which is packaged in such form or concentration, or Pub.L. ? Secretary of State, pursuant to article 2 or other with adulterants or denaturants, so that as pack- Pub.L. applicable provisions of the Convention, for review of aged it does not present any significant potential Pub.L. scheduling decisions under such Convention, based on Stat 20⁻ for abuse. new or additional information. Temporary scheduling to avoid imminent Immediate precursors hazards to public safety Refere (e) The Attorney General may, without regard to (h)(1) If the Attorney General finds that the sched- metic A June 25 the findings required by subsection (a) of this section uling of a substance in schedule I on a temporary basis is necessary to avoid an imminent hazard to the classified or section 812(b) of this title and without regard to 21, U.S.O. the procedures prescribed by subsections (a) and (b) public safety, he may, by order and without regard to Sched. of this section, place an immediate precursor in the the requirements of subsection (b) of this section are set same schedule in which the controlled substance of relating to the Secretary of Health and Human Ser The P: which it is an immediate precursor is placed or in any vices, schedule such substance in schedule I if the subsec. ( substance is not listed in any other schedule in seq which e other schedule with a higher numerical designation. tion 812 of this title or if no exemption or approval: U.S.C.A. If the Attorney General designates a substance as an immediate precursor and places it in a schedule, in effect for the substance under section 355 of this tions 852 title. Such an order may not be issued before and 965 other substances shall not be placed in a schedule The Pub' solely because they are its precursors. expiration of thirty days from- Complete Annotation Materials, see Title 21, U.S.C.A. 1046 Ch. 13 Ch. 13 DRUG ABUSE PREVENTION AND CONTROL 21 § 812 (A) the date of the publication by the Attorney out as notes under sections 801, 801a, 812, and 830 of Title tential General of a notice in the Federal Register of the 21. trug application is submit- intention to issue such order and the grounds upon Change of Name. "Secretary of Health and Human y drug having a stimulant, which such order is to be issued, and Services" was substituted for "Secretary of Health, Edu- nic effect on the central cation, and Welfare" on authority of Pub.L. 96-88, Title V, S that such drug has an (B) the date the Attorney General has transmit- § 509, Oct. 17, 1979, 93 Stat. 695, which is classified to mation shall be forwarded ted the notice required by paragraph (4). section 3508 of Title 20, U.S.C.A., Education. torney General. (2) The scheduling of a substance under this sub- Code of Federal Regulations section shall expire at the end of one year from the Administrative functions, practices, and procedures, see S sold over the counter date of the issuance of the order scheduling such 21 CFR 1316.01 et seq. dextromethorphan substance, except that the Attorney General may, Debarment and suspension, drug-free workplace, grants, neral shall by regulation during the pendency of proceedings under subsection see 21 CFR 1404.100 et seq. ibstance from a schedule if (a)(1) of this section with respect to the substance, Drug abuse prevention, audiovisual education, see 34 CFR the Federal Food, Drug, extend the temporary scheduling for up to six 763.1 et seq. fully sold over the counter months. Drug-free schools and campuses, see 34 CFR 86.1 et seq. (3) When issuing an order under paragraph (1), Mandatory declassification review program, see 21 CFR hall not be deemed to be the Attorney General shall be required to consider, 1402.1 et seq. y reason of enactment of with respect to the finding of an imminent hazard to Schedules, see 21 CFR 1308.01 et seq. and Table. ntrolled after October 27, the public safety, only those factors set forth in Uniform administrative requirements, grants and cooper- regoing provisions of this paragraphs (4), (5), and (6) of subsection (c) of this ative agreements, see 21 CFR 1403.1 et seq. section, including actual abuse, diversion from legiti- al may, by regulation, ex- mate channels, and clandestine importation, manufac- § 812. Schedules of controlled substances ire, or preparation contain- ture, or distribution. Establishment from the application of all (4) The Attorney General shall transmit notice of (a) There are established five schedules of con- apter if he finds such com- an order proposed to be issued under paragraph (1) ration meets the require- trolled substances, to be known as schedules I, II, to the Secretary of Health and Human Services. In III, IV, and V. Such schedules shall initially consist ing categories: issuing an order under paragraph (1), the Attorney of the substances listed in this section. The sched- eparation containing a non- General shall take into consideration any comments ules established by this section shall be updated and stance, which mixture or submitted by the Secretary in response to a notice republished on a semiannual basis during the two- 1 for prescription use, and transmitted pursuant to this paragraph. year period beginning one year after October 27, more other active ingredi- (5) An order issued under paragraph (1) with re- 1970 and shall be updated and republished on an 1 in any schedule and which spect to a substance shall be vacated upon the conclu- annual basis thereafter. such combinations, quantity, sion of a subsequent rulemaking proceeding initiated ation as to vitiate the poten- under subsection (a) of this section with respect to Placement on schedules; findings required such substance. (b) Except where control is required by United ture, or preparation which (6) An order issued under paragraph (1) is not States obligations under an international treaty, con- substance, which is not for subject to judicial review. vention, or protocol, in effect on October 27, 1970, and man being or animal, and (Pub.L. 91-513, Title II, § 201, Oct. 27, 1970, 84 Stat. 1245; except in the case of an immediate precursor, a drug ch form or concentration, or Pub.L. 95-633, Title I, § 102(a), Nov. 10, 1978, 92 Stat. 3769; or other substance may not be placed in any schedule naturants, so that as pack- Pub.L. 96-88, Title V, § 509, Oct. 17, 1979, 93 Stat. 695; unless the findings required for such schedule are nt any significant potential Pub.L. 98-473, Title II, §§ 508, 509(a), Oct. 12, 1984, 98 made with respect to such drug or other substance. Stat. 2071, 2072.) The findings required for each of the schedules are as follows: ng to avoid imminent EDITORIAL NOTES (1) Schedule I.— public safety References in Text. The Federal Food, Drug, and Cos- General finds that the sched metic Act, referred to in subsecs. (d)(3) and (g)(1), is Act (A) The drug or other substance has a high schedule I on a temporary June 25, 1938, c. 675, 52 Stat. 1040, as amended, which is potential for abuse. d an imminent hazard to the classified generally to chapter 9 (section 301 et seq.) of Title 21, U.S.C.A., Food and Drugs. (B) The drug or other substance has no current- order and without regard Schedules IV and V, referred to in subsec. (d)(4)(A), (B), ly accepted medical use in treatment in the United osection (b) of this section States. are set out in section 812(c) of this title. of Health and Human Ser The Psychotropic Substances Act of 1978, referred to in (C) There is a lack of accepted safety for use of stance in schedule I if the subsec. (d)(5), is Pub.L. 95-633, Nov. 11, 1978, 92 Stat. 3768, the drug or other substance under medical supervi- 1 any other schedule in ser which enacted sections 801a, 830, and 852 of Title 21, sion. no exemption or approvali U.S.C.A., Food and Drugs, amended this section and sec- ce under section 355 of this tions 352, 802, 812, 823, 827, 841 to 843, 872, 881, 952, 953, (2) Schedule II.- ay not be issued before and 965 of Title 21 and section 242a of Title 42, U.S.C.A., (A) The drug or other substance has a high The Public Health and Welfare, and enacted provisions set potential for abuse. from- Complete Annotation Materials, see Title 21, U.S.C.A. 1047 6< A Rohypnol Q What 15 this drug ? 6 the where IS if made? G How IS it getting In the Country? G What does Schedule IV mean ? 6 How can a drug's Schedule be Changed ? OFFICE THE NATIONAL PRESIDENT SIATES CONTRA MUNITED EXECUTIVE OFFICE OF THE PRESIDENT OFFICE OF NATIONAL DRUG CONTROL POLICY Washington, D.C. 20503 January 23, 1996 MEMORANDUM TO ELENA KAGAN DENNIS BURKE FROM: EDWARD H. JURITH EH) RE: ROHYPNOL I have further reviewed the law and legislative history surrounding 21 USC 811(h)(1) and the specific argument that the disjunctive nature of the statute would permit the Attorney General to place flunitrazepam (rohypnol) in Schedule 1 on an emergency basis. I ask that you consider the following case law and interpretations in deciding whether we can recommend using the emergency authority in this instance. First, a plain reading of the statute yields the conclusion that the AG could not temporarily schedule a substance if it was already in Schedules II-V or if it was subject to an IND or NDA under section 355 granted by FDA. Moreover the statute in issue talks in terms of the "scheduling" of a drug. What is being proposed is a "rescheduling" of an previously scheduled drug. Using 811 in this manner would do disruption to the entire CSA scheduling scheme. Second, can the AG temporarily place a drug in schedule I if it is not subject to a pending IND or NDA, even though it is listed in schedule IV? If that is correct, the converse would also be true -- the AG could place an FDA approved drug in schedule 1 if it is not already scheduled. I believe case law. logic, and the legislative history of the statute argue against this conclusion. In Grinspoon V. DEA, 828 F.2d 881 (lst Cir, 1987), the court in reviewing the provisions of the emergency scheduling authority noted: "This provision allows the Attorney General to place certain substances into schedule I on a temporary basis without regard to the regular scheduling criteria and procedures if such emergency scheduling is 'necessary to avoid an imminent hazard to public safety.' 21 USC 811(h)(1). This amendment to the CSA, however, expressly states that the Attorney 2. General's authority to schedule substances in this expedited manner does not apply where an "exemption or approval is in effect for the substances under section 355 of this title", i.e., where the FDA has permitted the substances to be marketed in interstate commerce." Substances listed in schedules II-V in Section 812 all share the criteria of having a currently accepted medical use in treatment. Grinspoon specifically rejected the notion that a substance must have FDA approval or exemption to have a currently accepted medical use. Thereafter, DEA adopted a five criteria test which would allow it to conclude a medically useful drug not marketed in the United States has a "currently accepted medical use" under the Controlled Substances Act. The test is as follows; the drug's chemistry must be known and reproducible; there must be adequate safety studies, there must be adequate and well controlled studies proving efficacy, acceptance by qualified experts is required, and the scientific evidence must be widely available. This five criteria test is set forth at 57 Fed. Reg, 10499-10508, March 26, 1992. In this notice DEA, specifically reference the fact that when the Controlled Substances Act was enacted, drugs with medical uses but without approved NDA's, were placed by Congress in Schedules II, III, IV and V. Citing Grinspoon, the notice states that "NDA approval is not the only method by which drugs can achieve Federal recognition as having medical uses" (at page 10504). Thus, under Grinspoon, if a substance is listed in schedule II - V under section 812 (regardless of whether it has an exemption or approval under section 355) it has an accepted medical use, or if a substance is subject to an approval or exemption under section 355, the AG may not list the substance in schedule I on an emergency basis. Legislative History Addressing concerns of medical treatment House Report 98-835 states: The Subcommittee believed that these concerns raised significant questions about the impact an emergency scheduling authority would have on the manufacture and distribution of drugs that are currently used in medical treatment. In examining the particular substance for which the scheduling action was most necessary, the Subcommittee concluded that limiting the authority only to substances that have no currently accepted medical use in treatment addressed both the legitimate 3. concerns of those in the health care industry and the principal danger to the public health. The stated congressional intent was to limit the effect of 811 (h) to substances that have no currently accepted medical use in treatment. In essence, being listed in schedules II-V, indicates that a substance has an accepted medical use, as do drugs having an FDA approval or exemption under section 355. Congress did not intend that medically useful drugs be subject to emergency scheduling in schedule I -- which the CSA reserves for substances that have no currently accepted medical uses. Practical Application Moreover, the practical use of the emergency authority has been limited to drugs which fall outside the current schedules or lack NDA or IND status under section 355. As the attached list illustrates, it has been directed at fentanyl and other "designer drug" analogs which have a high potential for abuse. This is not the case with medications that have been approved for medical use and otherwise scheduled. Conclusion Based on the above analysis, I do not believe we can utilize the emergency scheduling authority to "reschedule" rohypnol in Schedule I I suggest we explore the following alternatives: 1. Formal rescheduling of rohypnol to schedule II or III. This will ensure tighter controls over the drug from an administrative point of view. 2. Propose legislation that enhances Federal penalties for use of a controlled substance in connection with a sexual assault. OD AND DRUGS FOOD AND DRUGS 21 § 355 ing held to determine whether the Food and cross-examination by those opposing the actions Drug Administration acted rationally in requir- rug Administration has taken by the Food and Drug Administration. ing that preparations of vitamins A and D in National Nutritional Foods Ass'n V. Mathews, determine whether drug excess of specified dosages be restricted to pre- constitutes "new drug" D.C.N.Y.1976, 418 F.Supp. 394. scription sale and be labeled accordingly, for is expertise of Federal resolving technical and otics Research Corp. V. § 355. New drugs 710 F.2d 1375. (a) Necessity of effective approval of application doctrine," bulk supplier No person shall introduce or deliver for introduction into interstate commerce any ne (PTFE) to manufac- new drug, unless an approval of an application filed pursuant to subsection (b) or (j) of nt, which was regulated this section is effective with respect to such drug. Administration (FDA), 0 warn of possible dan- (b) Filing application; contents ant, and thus, patients (1) Any person may file with the Secretary an application with respect to any drug supplier for injuries al- It of implant, on breach subject to the provisions of subsection (a) of this section. Such person shall submit to FDA approved PTFE the Secretary as a part of the application (A) full reports of investigations which have levice for use in a medi- been made to show whether or not such drug is safe for use and whether such drug is illing the order, supplier effective in use; (B) a full list of the articles used as components of such drug; (C) a full of its lack of knowledge statement of the composition of such drug; (D) a full description of the methods used in, in implants was appro- and the facilities and controls used for, the manufacture, processing, and packing of such Inc., D.N.D.1992, 803 drug; (E) such samples of such drug and of the articles used as components thereof as the Secretary may require; and (F) specimens of the labeling proposed to be used for A) (5) (a), (A) (6) (a), (B) such drug. The applicant shall file with the application the patent number and the dministration of a drug expiration date of any patent which claims the drug for which the applicant submitted member of the medical iverside Hospital, 1974, the application or which claims a method of using such drug and with respect to which a App.2d 422. claim of patent infringement could reasonably be asserted if a person not licensed by the patient who contracted owner engaged in the manufacture, use, or sale of the drug. If an application is filed transfusion did not state under this subsection for a drug and a patent which claims such drug or a method of rainst hospital and blood using such drug is issued after the filing date but before approval of the application, the gence by reason of a applicant shall amend the application to include the information required by the 3715.01(A) (5) (a), (A) (6) preceding sentence. Upon approval of the application, the Secretary shall publish provisions thereof did information submitted under the two preceding sentences. ion of a drug or device medical profession. Id. (2) An application submitted under paragraph (1) for a drug for which the investiga- tions described in clause (A) of such paragraph and relied upon by the applicant for sufficiency approval of the application were not conducted by or for the applicant and for which the gh dosage quantities of applicant has not obtained a right of reference or use from the person by or for whom cure, mitigation, treat- the investigations were conducted shall also include- a variety of ailments, fact that there exists (A) a certification, in the opinion of the applicant and to the best of his f known nutritional re- knowledge, with respect to each patent which claims the drug for which such evels of 10,000 IU per investigations were conducted or which claims a use for such drug for which the and 400 IU per dosage applicant is seeking approval under this subsection and for which information is afficient to demonstrate required to be filed under paragraph (1) or subsection (c) of this section- Administration require- of vitamins A and D (i) that such patent information has not been filed, stricted to prescription (ii) that such patent has expired, ordingly was not arbi- (iii) of the date on which such patent will expire, or tional Nutritional Foods N.Y.1976, 418 F.Supp. (iv) that such patent is invalid or will not be infringed by the manufacture use, or sale of the new drug for which the application is submitted; and fficient to support find- (B) if with respect to the drug for which investigations described in paragraph preparations of certain (1)(A) were conducted information was filed under paragraph (1) or subsection (c) of trated usage as a food, this section for a method of use patent which does not claim a use for which the xtremely small percent- ove levels established in applicant is seeking approval under this subsection, a statement that the method of stration regulations re- use patent does not claim such a use. y preparations be avail- (3)(A) An applicant who makes a certification described in paragraph (2)(A)(iv) shall scription and be labeled include in the application a statement that the applicant will give the notice required by standing alone, be suffi- lations, it was a relevant subparagraph (B) to- avor of the regulations. (i) each owner of the patent which is the subject of the certification or the representative of such owner designated to receive such notice, and (ii) the holder of the approved application under subsection (b) of this section for and drugs would not be the drug which is claimed by the patent or a use of which is claimed by the patent hearing, which was be- or the representative of such holder designated to receive such notice. 175 21 § 355 FOOD AND DRUGS FOOD AND DRUGS (B) The notice referred to in subparagraph (A) shall state that an application has (i) if before the expiration of such period the cour been submitted under this subsection for the drug with respect to which the certification is invalid or not infringed, the approval may be ma is made to obtain approval to engage in the commercial manufacture, use, or sale of the the court decision, drug before the expiration of the patent referred to in the certification. Such notice (ii) if before the expiration of such period the cour shall include a detailed statement of the factual and legal basis of the applicant's opinion has been infringed, the approval may be made effe that the patent is not valid or will not be infringed. court orders under section 271(e)(4)(A) of Title 35, (C) If an application is amended to include a certification described in paragraph (iii) if before the expiration of such period the c (2)(A)(iv), the notice required by subparagraph (B) shall be given when the amended injunction prohibiting the applicant from engaging in application is submitted. ture or sale of the drug until the court decides the is infringement and if the court decides that such (c) Period for approval of application; period for, notice, and expedition of hearing; period for infringed, the approval shall be made effective or issuance of order decision. (1) Within one hundred and eighty days after the filing of an application under In such an action, each of the parties shall reasonably C( subsection (b) of this section, or such additional period as may be agreed upon by the action. Until the expiration of forty-five days from the d Secretary and the applicant, the Secretary shall either- paragraph (3)(B) is received, no action may be brought 1 (A) Approve the application if he then finds that none of the grounds for denying 28 for a declaratory judgment with respect to the pat approval specified in subsection (d) of this section applies, or under such section 2201 shall be brought in the judicial di (B) Give the applicant notice of an opportunity for a hearing before the Secre- has its principal place of business or a regular and esta tary under subsection (d) of this section on the question whether such application is (D)(i) If an application (other than an abbreviated new approvable. If the applicant elects to accept the opportunity for hearing by written ted under subsection (b) of this section for a drug, no a request within thirty days after such notice, such hearing shall commence not more any ester or salt of the active ingredient) of which has be than ninety days after the expiration of such thirty days unless the Secretary and application under subsection (b) of this section, was ap the applicant otherwise agree. Any such hearing shall thereafter be conducted on beginning January 1, 1982, and ending on September 24 an expedited basis and the Secretary's order thereon shall be issued within ninety not make the approval of another application for a drug f days after the date fixed by the Secretary for filing final briefs. described in clause (A) of subsection (b)(1) of this sectic (2) If the patent information described in subsection (b) of this section could not be applicant for approval of the application were not conduct filed with the submission of an application under subsection (b) of this section because and for which the applicant has not obtained a right of person by or for whom the investigations were condu the application was filed before the patent information was required under subsection (b) expiration of ten years from the date of the approval of of this section or a patent was issued after the application was approved under such approved under subsection (b) of this section. subsection, the holder of an approved application shall file with the Secretary the patent number and the expiration date of any patent which claims the drug for which the (ii) If an application submitted under subsection (b) of application was submitted or which claims a method of using such drug and with respect active ingredient (including any ester or salt of the active to which a claim of patent infringement could reasonably be asserted if a person not been approved in any other application under subsect: licensed by the owner engaged in the manufacture, use, or sale of the drug. If the approved after September 24, 1984, no application whi holder of an approved application could not file patent information under subsection (b) which the subsection (b) application was submitted and fc of this section because it was not required at the time the application was approved, the described in clause (A) of subsection (b)(1) of this sectic holder shall file such information under this subsection not later than thirty days after applicant for approval of the application were not conduct September 24, 1984, and if the holder of an approved application could not file patent and for which the applicant has not obtained a right of information under subsection (b) of this section because no patent had been issued when person by or for whom the investigations were conducte an application was filed or approved, the holder shall file such information under this subsection (b) of this section before the expiration of five subsection not later than thirty days after the date the patent involved is issued. Upon approval of the application under subsection (b) of this BE the submission of patent information under this subsection, the Secretary shall publish application may be submitted under subsection (b) of thi it. tion of four years from the date of the approval of the sub contains a certification of patent invalidity or noninfring (3) The approval of an application filed under subsection (b) of this section which (iv) of subsection (b)(2)(A) of this section. The approval C contains a certification required by paragraph (2) of such subsection shall be made be made effective in accordance with this paragraph ex effective on the last applicable date determined under the following: patent infringement is commenced during the one-year pe (A) If the applicant only made a certification described in clause (i) or (ii) of months after the date of the approval of the subsection subsection (b)(2)(A) of this section or in both such clauses, the approval may be month period referred to in subparagraph (C) shall be ex made effective immediately. time (if any) which is required for seven and one-half ye (B) If the applicant made a certification described in clause (iii) of subsection the date of approval of the subsection (b) application. (b)(2)(A) of this section, the approval may be made effective on the date certified (iii) If an application submitted under subsection (b) under clause (iii). which includes an active ingredient (including any est (C) If the applicant made a certification described in clause (iv) of subsection ingredient) that has been approved in another applicatio (b)(2)(A) of this section, the approval shall be made effective immediately unless an tion (b) of this section, is approved after September 24, 19 action is brought for infringement of a patent which is the subject of the certifica- contains reports of new clinical investigations (other th tion before the expiration of forty-five days from the date the notice provided under essential to the approval of the application and conduc paragraph (3)(B) is received. If such an action is brought before the expiration of applicant, the Secretary may not make the approval of such days, the approval may be made effective upon the expiration of the thirty- under subsection (b) of this section for the conditions of ap month period beginning on the date of the receipt of the notice provided under approved subsection (b) application effective before the paragraph (3)(B) or such shorter or longer period as the court may order because from the date of the approval of the application under sur either party to the action failed to reasonably cooperate in expediting the action, if the investigations described in clause (A) of subsection except that- relied upon by the applicant for approval of the applicati 176 177 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 in subparagraph (A) shall state that an application has (i) if before the expiration of such period the court decides that such patent ection for the drug with respect to which the certification is invalid or not infringed, the approval may be made effective on the date of ngage in the commercial manufacture, use, or sale of the the court decision, the patent referred to in the certification. Such notice (ii) if before the expiration of such period the court decides that such patent nt of the factual and legal basis of the applicant's opinion has been infringed, the approval may be made effective on such date as the will not be infringed. court orders under section 271(e)(4)(A) of Title 35, or ended to include a certification described in paragraph (iii) if before the expiration of such period the court grants a preliminary by subparagraph (B) shall be given when the amended injunction prohibiting the applicant from engaging in the commercial manufac- ture or sale of the drug until the court decides the issues of patent validity and infringement and if the court decides that such patent is invalid or not tion; period for, notice, and expedition of hearing; period for infringed, the approval shall be made effective on the date of such court decision. d eighty days after the filing of an application under In such an action, each of the parties shall reasonably cooperate in expediting the or such additional period as may be agreed upon by the action. Until the expiration of forty-five days from the date the notice made under ne Secretary shall either- paragraph (3)(B) is received, no action may be brought under section 2201 of Title tion if he then finds that none of the grounds for denying 28 for a declaratory judgment with respect to the patent. Any action brought ection (d) of this section applies, or under such section 2201 shall be brought in the judicial district where the defendant notice of an opportunity for a hearing before the Secre- has its principal place of business or a regular and established place of business. of this section on the question whether such application is (D)(i) If an application (other than an abbreviated new drug application) submit- nt elects to accept the opportunity for hearing by written ted under subsection (b) of this section for a drug, no active ingredient (including after such notice, such hearing shall commence not more any ester or salt of the active ingredient) of which has been approved in any other expiration of such thirty days unless the Secretary and application under subsection (b) of this section, was approved during the period ree. Any such hearing shall thereafter be conducted on beginning January 1, 1982, and ending on September 24, 1984, the Secretary may e Secretary's order thereon shall be issued within ninety not make the approval of another application for a drug for which the investigations by the Secretary for filing final briefs. described in clause (A) of subsection (b)(1) of this section and relied upon by the n described in subsection (b) of this section could not be applicant for approval of the application were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the 1 application under subsection (b) of this section because person by or for whom the investigations were conducted effective before the the patent information was required under subsection (b) expiration of ten years from the date of the approval of the application previously S issued after the application was approved under such approved under subsection (b) of this section. proved application shall file with the Secretary the patent ite of any patent which claims the drug for which the (ii) If an application submitted under subsection (b) of this section for a drug, no hich claims a method of using such drug and with respect active ingredient (including any ester or salt of the active ingredient) of which has ringement could reasonably be asserted if a person not been approved in any other application under subsection (b) of this section, is d in the manufacture, use. or sale of the drug. If the approved after September 24, 1984, no application which refers to the drug for ion could not file patent information under subsection (b) which the subsection (b) application was submitted and for which the investigations described in clause (A) of subsection (b)(1) of this section and relied upon by the :ot required at the time the application was approved. the ion under this subsection not later than thirty days after applicant for approval of the application were not conducted by or for the applicant e holder of an approved application could not file patent and for which the applicant has not obtained a right of reference or use from the 5) of this section because no patent had been issued when person by or for whom the investigations were conducted may be submitted under subsection (b) of this section before the expiration of five years from the date of the proved. the holder shall file such information under this days after the date the patent involved is issued. Upon approval of the application under subsection (b) of this section, except that such an mation under this subsection, the Secretary shall publish application may be submitted under subsection (b) of this section after the expira- tion of four years from the date of the approval of the subsection (b) application if it contains a certification of patent invalidity or noninfringement described in clause lication filed under subsection (b) of this section which (iv) of subsection (b)(2)(A) of this section. The approval of such an application shall ed by paragraph (2) of such subsection shall be made be made effective in accordance with this paragraph except that, if an action for date determined under the following: patent infringement is commenced during the one-year period beginning forty-eight ily made a certification described in clause (i) or (ii) of months after the date of the approval of the subsection (b) application, the thirty- is section or in both such clauses. the approval may be month period referred to in subparagraph (C) shall be extended by such amount of ly. time (if any) which is required for seven and one-half years to have elapsed from ade a certification described in clause (iii) of subsection the date of approval of the subsection (b) application. he approval may be made effective on the date certified (iii) If an application submitted under subsection (b) of this section for a drug, which includes an active ingredient (including any ester or salt of the active ade a certification described in clause (iv) of subsection ingredient) that has been approved in another application approved under subsec- he approval shall be made effective immediately unless an tion (b) of this section, is approved after September 24, 1984, and if such application ngement of a patent which is the subject of the certifica- contains reports of new clinical investigations (other than bioavailability studies) of forty-five days from the date the notice provided under essential to the approval of the application and conducted or sponsored by the ed. If such an action is brought before the expiration of applicant, the Secretary may not make the approval of an application submitted may be made effective upon the expiration of the thirty- under subsection (b) of this section for the conditions of approval of such drug in the on the date of the receipt of the notice provided under approved subsection (b) application effective before the expiration of three years shorter or longer period as the court may order because from the date of the approval of the application under subsection (b) of this section 1 failed to reasonably cooperate in expediting the action. if the investigations described in clause (A) of subsection (b)(1) of this section and relied upon by the applicant for approval of the application were not conducted by 176 177 21 § 355 FOOD AND DRUGS FOOD AND DRUGS or for the applicant and if the applicant has not obtained a right of reference or use application was approved; (2) that new evider from the person by or for whom the investigations were conducted. such application or not available to the Se (iv) If a supplement to an application approved under subsection (b) of this approved. or tests by new methods, or te section is approved after September 24, 1984, and the supplement contains reports applicable when such application was approv of new clinical investigations (other than bioavailability studies) essential to the available to the Secretary when the applicatio approval of the supplement and conducted or sponsored by the person submitting not shown to be safe for use under the cond the supplement, the Secretary may not make the approval of an application application was approved; or (3) on the basis 0: submitted under subsection (b) of this section for a change approved in the to such drug, evaluated together with the evide supplement effective before the expiration of three years from the date of the was approved, that there is a lack of substan: approval of the supplement under subsection (b) of this section if the investigations effect it purports or is represented to have described in clause (A) of subsection (b)(1) of this section and relied upon by the recommended, or suggested in the labeling applicant for approval of the application were not conducted by or for the applicant prescribed by subsection (c) of this section W and if the applicant has not obtained a right of reference or use from the person by receipt of written notice from the Secretary S] or for whom the investigations were conducted. tion; or (5) that the at the application contains (v) If an application (or supplement to an application) submitted under subsection Provided, That if the Secretary (or in his abse (b) of this section for a drug, which includes an active ingredient (including any that there is an imminent hazard to the public ester or salt of the active ingredient) that has been approved in another application such application immediately, and give the a] under subsection (b) of this section, was approved during the period beginning afford the applicant the opportunity for an exp. January 1, 1982, and ending on September 24, 1984, the Secretary may not make the authority conferred by this proviso to sus the approval of an application submitted under this subsection and for which the not be delegated. The Secretary may also, aft. investigations described in clause (A) of subsection (b)(1) of this section and relied to the applicant, withdraw the approval of an a. upon by the applicant for approval of the application were not conducted by or for or (j) of this section with respect to any drug u: the applicant and for which the applicant has not obtained a right of reference or that the applicant has failed to establish a sys use from the person by or for whom the investigations were conducted and which has repeatedly or deliberately failed to main refers to the drug for which the subsection (b) application was submitted effective reports, in accordance with a regulation or ord before the expiration of two years from September 24, 1984. to comply with the notice requirements of secti has refused to permit access to, or copying or V (d) Grounds for refusing application; approval of application; "substantial evidence" defined paragraph (2) of such subsection; or (2) that on If the Secretary finds, after due notice to the applicant in accordance with subsection evaluated together with the evidence before hin (c) of this section and giving him an opportunity for a hearing, in accordance with said methods used in, or the facilities and controls u: subsection, that (1) the investigations, reports of which are required to be submitted to packing of such drug are inadequate to assu the Secretary pursuant to subsection (b) of this section, do not include adequate tests by quality. and purity and were not made adequate all methods reasonably applicable to show whether or not such drug is safe for use written notice from the Secretary specifying the under the conditions prescribed, recommended, or suggested in the proposed labeling basis of new information before him, evaluated thereof; (2) the results of such tests show that such drug is unsafe for use under such when the application was approved, the labeling conditions or do not show that such drug is safe for use under such conditions; (3) the of all material facts, is false or misleading in any methods used in, and the facilities and controls used for, the manufacture, processing, a reasonable time after receipt of written no and packing of such drug are inadequate to preserve its identity, strength, quality, and matter complained of. Any order under this purity; (4) upon the basis of the information submitted to him as part of the application, which it is based. or upon the basis of any other information before him with respect to such drug, he has insufficient information to determine whether such drug is safe for use under such [See main volume for conditions; or (5) evaluated on the basis of the information submitted to him as part of (j) Abbreviated new drug applications the application and any other information before him with respect to such drug, there is a lack of substantial evidence that the drug will have the effect it purports or is (1) Any person may file with the Secreta represented to have under the conditions of use prescribed, recommended, or suggested approval of a new drug. in the proposed labeling thereof; or (6) the application failed to contain the patent (2)(A) An abbreviated application for a new information prescribed by subsection (b) of this section; or (7) based on a fair evaluation (i) information to show that the conditic of all material facts, such labeling is false or misleading in any particular; he shall issue suggested in the labeling proposed for the n an order refusing to approve the application. If, after such notice and opportunity for for a drug listed under paragraph (6) (hereir hearing, the Secretary finds that clauses (1) through (6) do not apply, he shall issue an "listed drug"); order approving the application. As used in this subsection and subsection (e) of this (ii)(I) if the listed drug referred to in ci section, the term "substantial evidence" means evidence consisting of adequate and well- controlled investigations, including clinical investigations, by experts qualified by scienti- information to show that the active ingredier the listed drug; fic training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly and responsibly be concluded by such experts that the drug (II) if the listed drug referred to in will have the effect it purports or is represented to have under the conditions of use ingredient, information to show that the act prescribed, recommended, or suggested in the labeling or proposed labeling thereof. same as those of the listed drug, or (III) if the listed drug referred to in (e) Withdrawal of approval; grounds; immediate suspension upon finding imminent hazard to ingredient and if one of the active ingredier public health application is filed pursuant to the approval The Secretary shall, after due notice and opportunity for hearing to the applicant, (C), information to show that the other acti- withdraw approval of an application with respect to any drug under this section if the same as the active ingredients of the liste Secretary finds (1) that clinical or other experience, tests, or other scientific data show different active ingredient is an active ingred that such drug is unsafe for use under the conditions of use upon the basis of which the does not meet the requirements of sectio. 178 179 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 icant has not obtained a right of reference or use application was approved; (2) that new evidence of clinical experience, not contained in he investigations were conducted. such application or not available to the Secretary until after such application was plication approved under subsection (b) of this approved. or tests by new methods, or tests by methods not deemed reasonably er 24, 1984. and the supplement contains reports applicable when such application was approved, evaluated together with the evidence er than bioavailability studies) essential to the available to the Secretary when the application was approved, shows that such drug is onducted or sponsored by the person submitting not shown to be safe for use under the conditions of use upon the basis of which the may not make the approval of an application application was approved; or (3) on the basis of new information before him with respect of this section for a change approved in the to such drug, evaluated together with the evidence available to him when the application expiration of three years from the date of the was approved, that there is a lack of substantial evidence that the drug will have the subsection (b) of this section if the investigations effect it purports or is represented to have under the conditions of use prescribed, tion (b)(1) of this section and relied upon by the recommended, or suggested in the labeling thereof; or (4) the patent information cation were not conducted by or for the applicant prescribed by subsection (c) of this section was not filed within thirty days after the ed a right of reference or use from the person by receipt of written notice from the Secretary specifying the failure to file such informa- ere conducted. tion; or (5) that the at the application contains any untrue statement of a material fact: nent to an application) submitted under subsection Provided, That if the Secretary (or in his absence the officer acting as Secretary) finds hich includes an active ingredient (including any that there is an imminent hazard to the public health, he may suspend the approval of ent) that has been approved in another application such application immediately, and give the applicant prompt notice of his action and tion, was approved during the period beginning afford the applicant the opportunity for an expedited hearing under this subsection; but September 24, 1984, the Secretary may not make the authority conferred by this proviso to suspend the approval of an application shall abmitted under this subsection and for which the not be delegated. The Secretary may also, after due notice and opportunity for hearing (A) of subsection (b)(1) of this section and relied to the applicant. withdraw the approval of an application submitted under subsection (b) al of the application were not conducted by or for or (j) of this section with respect to any drug under this section if the Secretary finds (1) applicant has not obtained a right of reference or that the applicant has failed to establish a system for maintaining required records, or hom the investigations were conducted and which has repeatedly or deliberately failed to maintain such records or to make required subsection (b) application was submitted effective reports. in accordance with a regulation or order under subsection (k) of this section or rs from September 24, 1984. to comply with the notice requirements of section 360(k)(2) of this title, or the applicant has refused to permit access to, or copying or verification of, such records as required by pproval of application; "substantial evidence" defined paragraph (2) of such subsection; or (2) that on the basis of new information before him, tice to the applicant in accordance with subsection evaluated together with the evidence before him when the application was approved, the opportunity for a hearing, in accordance with said methods used in, or the facilities and controls used for, the manufacture, processing, and ; reports of which are required to be submitted to packing of such drug are inadequate to assure and preserve its identity, strength, (b) of this section, do not include adequate tests by quality, and purity and were not made adequate within a reasonable time after receipt of ) show whether or not such drug is safe for use written notice from the Secretary specifying the matter complained of; or (3) that on the ommended. or suggested in the proposed labeling basis of new information before him, evaluated together with the evidence before him show that such drug is unsafe for use under such when the application was approved, the labeling of such drug, based on a fair evaluation drug is safe for use under such conditions; (3) the of all material facts, is false or misleading in any particular and was not corrected within nd controls used for, the manufacture. processing, a reasonable time after receipt of written notice from the Secretary specifying the uate to preserve its identity, strength, quality, and matter complained of. Any order under this subsection shall state the findings upon rmation submitted to him as part of the application. which it is based. nation before him with respect to such drug, he has [See main volume for text of (f) to (i)] e whether such drug is safe for use under such asis of the information submitted to him as part of (j) Abbreviated new drug applications ation before him with respect to such drug, there is : the drug will have the effect it purports or is (1) Any person may file with the Secretary an abbreviated application for the tions of use prescribed, recommended, or suggested approval of a new drug. or (6) the application failed to contain the patent (2)(A) An abbreviated application for a new drug shall contain- n (b) of this section; or (7) based on a fair evaluation (i) information to show that the conditions of use prescribed, recommended, or false or misleading in any particular: he shall issue suggested in the labeling proposed for the new drug have been previously approved oplication. If. after such notice and opportunity for for a drug listed under paragraph (6) (hereinafter in this subsection referred to as a auses (1) through (6) do not apply, he shall issue an "listed drug"); is used in this subsection and subsection (e) of this (ii)(I) if the listed drug referred to in clause (i) has only one active ingredient, ice" means evidence consisting of adequate and well- information to show that the active ingredient of the new drug is the same as that of linical investigations, by experts qualified by scienti- the listed drug; uate the effectiveness of the drug involved, on the sponsibly be concluded by such experts that the drug (II) if the listed drug referred to in clause (i) has more than one active is represented to have under the conditions of use ingredient, information to show that the active ingredients of the new drug are the rested in the labeling or proposed labeling thereof. same as those of the listed drug, or (III) if the listed drug referred to in clause (i) has more than one active immediate suspension upon finding imminent hazard to ingredient and if one of the active ingredients of the new drug is different and the application is filed pursuant to the approval of a petition filed under subparagraph notice and opportunity for hearing to the applicant. (C), information to show that the other active ingredients of the new drug are the in with respect to any drug under this section if the same as the active ingredients of the listed drug, information to show that the other experience. tests, or other scientific data show different active ingredient is an active ingredient of a listed drug or of a drug which der the conditions of use upon the basis of which the does not meet the requirements of section 321(p) of this title, and such other 178 179 21 § 355 FOOD AND DRUGS FOOD AND DRUGS information respecting the different active ingredient with respect to which the petition was filed as the Secretary may require; seeking permission to file such an application. prove a petition submitted under this subparagr. (iii) information to show that the route of administration, the dosage form, and petition is submitted. The Secretary shall appro the strength of the new drug are the same as those of the listed drug referred to in finds- clause (i) or, if the route of administration, the dosage form, or the strength of the new drug is different and the application is filed pursuant to the approval of a (i) that investigations must be conducted petition filed under subparagraph (C), such information respecting the route of the drug or of any of its active ingredients, 1 administration, dosage form, or strength with respect to which the petition was filed form, or strength which differ from the liste as the Secretary may require; (ii) that any drug with a different activ (iv) information to show that the new drug is bioequivalent to the listed drug evaluated for approval as safe and effective 0 referred to in clause (i), except that if the application is filed pursuant to the to be submitted in an abbreviated application approval of a petition filed under subparagraph (C), information to show that the (3) Subject to paragraph (4), the Secretary st active ingredients of the new drug are of the same pharmacological or therapeutic unless the Secretary finds- class as those of the listed drug referred to in clause (i) and the new drug can be (A) the methods used in, or the facilities a expected to have the same therapeutic effect as the listed drug when administered to patients for a condition of use referred to in clause (i); processing, and packing of the drug are is identity, strength, quality, and purity; (v) information to show that the labeling proposed for the new drug is the same as the labeling approved for the listed drug referred to in clause (i) except for (B) information submitted with the applica changes required because of differences approved under a petition filed under the proposed conditions of use have been p: subparagraph (C) or because the new drug and the listed drug are produced or referred to in the application; distributed by different manufacturers; (C)(i) if the listed drug has only one ac: (vi) the items specified in clauses (B) through (F) of subsection (b)(1) of this with the application is insufficient to show th section; that of the listed drug; (vii) a certification, in the opinion of the applicant and to the best of his (ii) if the listed drug has more than one a knowledge, with respect to each patent which claims the listed drug referred to in with the application is insufficient to show th clause (i) or which claims a use for such listed drug for which the applicant is as the active ingredients of the listed drug, seeking approval under this subsection and for which information is required to be (iii) if the listed drug has more than one filed under subsection (b) or (c) of this section- is for a drug which has an active ingre (I) that such patent information has not been filed, information submitted with the application is (II) that such patent has expired, (I) that the other active ingredients ar the listed drug, or (III) of the date on which such patent will expire, or (IV) that such patent is invalid or will not be infringed by the manufacture, (II) that the different active ingredie drug or 8 drug which does not meet the use, or sale of the new drug for which the application is submitted; and title, (viii) if with respect to the listed drug referred to in clause (i) information was filed under subsection (b) or (c) of this section for a method of use patent which or no petition to file an application for does not claim a use for which the applicant is seeking approval under this was approved under paragraph (2)(C); subsection. a statement that the method of use patent does not claim such a use. (D)(i) if the application is for a drug whos- or strength of the drug is the same as the rc The Secretary may not require that an abbreviated application contain information in strength of the listed drug referred to in the addition to that required by clauses (i) through (viii). the application is insufficient to show that the (B)(i) An applicant who makes a certification described in subparagraph (A)(vii)(IV) or strength is the same as that of the listed shall include in the application a statement that the applicant will give the notice (ii) if the application is for a drug whose r required by clause (ii) to- strength of the drug is different from that (I) each owner of the patent which is the subject of the certification or the application, no petition to file an application f representative of such owner designated to receive such notice, and administration, dosage form, or strength W. (II) the holder of the approved application under subsection (b) of this section for (E) if the application was filed pursuant the drug which is claimed by the patent or a use of which is claimed by the patent paragraph (2)(C), the application did not con or the representative of such holder designated to receive such notice. Secretary respecting the active ingredient, rc (ii) The notice referred to in clause (i) shall state that an application, which contains strength which is not the same; data from bioavailability or bioequivalence studies, has been submitted under this (F) information submitted in the applicatic subsection for the drug with respect to which the certification is made to obtain approval is bioequivalent to the listed drug referred to to engage in the commercial manufacture, use, or sale of such drug before the expiration was filed pursuant to a petition approved of the patent referred to in the certification. Such notice shall include a detailed submitted in the application is insufficient to statement of the factual and legal basis of the applicant's opinion that the patent is not new drug are of the same pharmacological or valid or will not be infringed. drug referred to in paragraph (2)(A)(i) and 1 (iii) If an application is amended to include a certification described in subparagraph have the same therapeutic effect as the liste (A)(vii)(IV), the notice required by clause (ii) shall be given when the amended for a condition of use referred to in such pa: application is submitted. (G) information submitted in the applica (C) If a person wants to submit an abbreviated application for a new drug which has labeling proposed for the drug is the same 8 a different active ingredient or whose route of administration, dosage form. or strength drug referred to in the application except fc differ from that of a listed drug, such person shall submit a petition to the Secretary ences approved under a petition filed under and the listed drug are produced or dist 180 Bk88 USCA 1994 P.P.-7 181 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 rent active ingredient with respect to which the seeking permission to file such an application. The Secretary shall approve or disap- ry may require; prove a petition submitted under this subparagraph within ninety days of the date the the route of administration, the dosage form, and petition is submitted. The Secretary shall approve such a petition unless the Secretary the same as those of the listed drug referred to in finds— inistration, the dosage form, or the strength of the application is filed pursuant to the approval of a (i) that investigations must be conducted to show the safety and effectiveness of ph (C), such information respecting the route of the drug or of any of its active ingredients, the route of administration, the dosage trength with respect to which the petition was filed form, or strength which differ from the listed drug; or (ii) that any drug with a different active ingredient may not be adequately the new drug is bioequivalent to the listed drug evaluated for approval as safe and effective on the basis of the information required t that if the application is filed pursuant to the to be submitted in an abbreviated application. r subparagraph (C), information to show that the (3) Subject to paragraph (4), the Secretary shall approve an application for a drug ug are of the same pharmacological or therapeutic unless the Secretary finds— referred to in clause (i) and the new drug can be (A) the methods used in, or the facilities and controls used for, the manufacture, peutic effect as the listed drug when administered processing, and packing of the drug are inadequate to assure and preserve its e referred to in clause (i); identity, strength, quality, and purity; he labeling proposed for the new drug is the same (B) information submitted with the application is insufficient to show that each of e listed drug referred to in clause (i) except for ifferences approved under a petition filed under the proposed conditions of use have been previously approved for the listed drug e new drug and the listed drug are produced or referred to in the application; turers; (C)(i) if the listed drug has only one active ingredient, information submitted Juses (B) through (F) of subsection (b)(1) of this with the application is insufficient to show that the active ingredient is the same as that of the listed drug; pinion of the applicant and to the best of his (ii) if the listed drug has more than one active ingredient, information submitted patent which claims the listed drug referred to in with the application is insufficient to show that the active ingredients are the same e for such listed drug for which the applicant is as the active ingredients of the listed drug, or section and for which information is required to be (iii) if the listed drug has more than one active ingredient and if the application of this section- is for a drug which has an active ingredient different from the listed drug, mation has not been filed, information submitted with the application is insufficient to show- expired, (I) that the other active ingredients are the same as the active ingredients of the listed drug, or h such patent will expire, or (II) that the different active ingredient is an active ingredient of a listed invalid or will not be infringed by the manufacture, drug or a drug which does not meet the requirements of section 321(p) of this rug for which the application is submitted; and title. sted drug referred to in clause (i) information was or no petition to file an application for the drug with the different ingredient of this section for a method of use patent which was approved under paragraph (2)(C); ch the applicant is seeking approval under this method of use patent does not claim such a use. (D)(i) if the application is for a drug whose route of administration. dosage form, or strength of the drug is the same as the route of administration. dosage form, or : an abbreviated application contain information in strength of the listed drug referred to in the application, information submitted in (i) through (viii). the application is insufficient to show that the route of administration, dosage form, certification described in subparagraph (A)(vii)(IV) or strength is the same as that of the listed drug, or statement that the applicant will give the notice (ii) if the application is for a drug whose route of administration, dosage form. or strength of the drug is different from that of the listed drug referred to in the t which is the subject of the certification or the application. no petition to file an application for the drug with the different route of esignated to receive such notice, and administration, dosage form. or strength was approved under paragraph (2)(C); d application under subsection (b) of this section for (E) if the application was filed pursuant to the approval of a petition under e patent or a use of which is claimed by the patent paragraph (2)(C), the application did not contain the information required by the older designated to receive such notice. Secretary respecting the active ingredient, route of administration, dosage form. or se (i) shall state that an application, which contains strength which is not the same; livalence studies, has been submitted under this (F) information submitted in the application is insufficient to show that the drug to which the certification is made to obtain approval is bioequivalent to the listed drug referred to in the application or, if the application ture, use, or sale of such drug before the expiration was filed pursuant to a petition approved under paragraph (2)(C), information ertification. Such notice shall include a detailed submitted in the application is insufficient to show that the active ingredients of the sis of the applicant's opinion that the patent is not new drug are of the same pharmacological or therapeutic class as those of the listed drug referred to in paragraph (2)(A)(i) and that the new drug can be expected to to include a certification described in subparagraph have the same therapeutic effect as the listed drug when administered to patients y clause (ii) shall be given when the amended for a condition of use referred to in such paragraph; (G) information submitted in the application is insufficient to show that the n abbreviated application for a new drug which has labeling proposed for the drug is the same as the labeling approved for the listed se route of administration, dosage form, or strength drug referred to in the application except for changes required because of differ- ich person shall submit a petition to the Secretary ences approved under a petition filed under paragraph (2)(C) or because the drug and the listed drug are produced or distributed by different manufacturers; 180 181 Bk88 USCA 1994 P.P.-7 21 § 355 FOOD AND DRUGS FOOD AND DRUGS (H) information submitted in the application or any other information available to (I) the date the Secretary receiv the Secretary shows that (i) the inactive ingredients of the drug are unsafe for use previous application of the first com under the conditions prescribed, recommended, or suggested in the labeling pro- previous application, or posed for the drug, or (ii) the composition of the drug is unsafe under such (II) the date of a decision of a C conditions because of the type or quantity of inactive ingredients included or the holding the patent which is the subje manner in which the inactive ingredients are included; infringed, (I) the approval under subsection (c) of this section of the listed drug referred to whichever is earlier. in the application under this subsection has been withdrawn or suspended for grounds described in the first sentence of subsection (e) of this section, the (C) If the Secretary decides to disapprove a Secretary has published a notice of opportunity for hearing to withdraw approval of applicant notice of an opportunity for a hearin the listed drug under subsection (c) of this section for grounds described in the first whether such application is approvable. If the sentence of subsection (e) of this section, the approval under this subsection of the for hearing by written request within thirty ( listed drug referred to in the application under this subsection has been withdrawn commence not more than ninety days after the or suspended under paragraph (5), or the Secretary has determined that the listed Secretary and the applicant otherwise agree drug has been withdrawn from sale for safety or effectiveness reasons; conducted on an expedited basis and the Secre ninety days after the date fixed by the Secret (J) the application does not meet any other requirement of paragraph (2)(A); or (K) the application contains an untrue statement of material fact. (D)(i) If an application (other than an abb under subsection (b) of this section for a drug (4)(A) Within one hundred and eighty days of the initial receipt of an application or salt of the active ingredient) of which has under paragraph (2) or within such additional period as may be agreed upon by the under subsection (b) of this section, was appro Secretary and the applicant, the Secretary shall approve or disapprove the application. 1, 1982. and ending on September 24, 1984, the (B) The approval of an application submitted under paragraph (2) shall be made an application submitted under this subsectio effective on the last applicable date determined under the following: subsection (b) application was submitted effect. (i) If the applicant only made a certification described in subclause (I) or (II) of the date of the approval of the applicatio paragraph (2)(A)(vii) or in both such subclauses, the approval may be made effective (ii) If an application submitted under subs immediately. active ingredient (including any ester or salt 0 (ii) If the applicant made a certification described in subclause (III) of paragraph approved in any other application under subse (2)(A)(vii), the approval may be made effective on the date certified under subclause September 24, 1984, no application may be sub (III). to the drug for which the subsection (b) applic (iii) If the applicant made a certification described in subclause (IV) of para- of five years from the date of the approval of t graph (2)(A)(vii), the approval shall be made effective immediately unless an action section, except that such an application may be is brought for infringement of a patent which is the subject of the certification expiration of four years from the date of the at before the expiration of forty-five days from the date the notice provided under it contains a certification of patent invalidity 0 paragraph (2)(B)(i) is received. If such an action is brought before the expiration of (IV) of paragraph (2)(A)(vii). The approval such days, the approval shall be made effective upon the expiration of the thirty- effective in accordance with subparagraph ( month period beginning on the date of the receipt of the notice provided under infringement is commenced during the one-y paragraph (2)(B)(i) or such shorter or longer period as the court may order because after the date of the approval of the subsectio either party to the action failed to reasonably cooperate in expediting the action, referred to in subparagraph (B)(iii) shall be e except that- which is required for seven and one-half years (I) if before the expiration of such period the court decides that such patent of the subsection (b) application. is invalid or not infringed. the approval shall be made effective on the date of (iii) If an application submitted under subs the court decision, includes an active ingredient (including any e: (II) if before the expiration of such period the court decides that such patent has been approved in another application appr has been infringed, the approval shall be made effective on such date as the is approved after September 24, 1984, and if court orders under section 271(e)(4)(A) of Title 35 or clinical investigations (other than bioavailabilit application and conducted or sponsored by th. (III) if before the expiration of such period the court grants a preliminary the approval of an application submitted unc injunction prohibiting the applicant from engaging in the commercial manufac- approval of such drug in the subsection (b) app ture or sale of the drug until the court decides the issues of patent validity and infringement and if the court decides that such patent is invalid or not three years from the date of the approval of th section for such drug. infringed, the approval shall be made effective on the date of such court decision. (iv) If a supplement to an application appro In such an action, each of the parties shall reasonably cooperate in expediting approved after September 24, 1984, and the su the action. Until the expiration of forty-five days from the date the notice investigations (other than bioavailability stu made under paragraph (2)(B)(i) is received, no action may be brought under supplement and conducted or sponsored by th section 2201 of Title 28 for a declaratory judgment with respect to the patent. Secretary may not make the approval of an ap Any action brought under section 2201 shall be brought in the judicial district for a change approved in the supplement effe where the defendant has its principal place of business or a regular and from the date of the approval of the supplem established place of business. (v) If an application (or supplement to an an (iv) If the application contains a certification described in subclause (IV) of of this section for a drug, which includes an act paragraph (2)(A)(vii) and is for a drug for which a previous application has been of the active ingredient) that has been approve submitted under this subsection continuing such a certification, the application shall (b) of this section, was approved during the be made effective not earlier than one hundred and eighty days after- ending on September 24, 1984, the Secreta 182 183 FOOD AND DRUGS FOOD AND DRUGS 21 § 355 ed in the application or any other information available to (I) the date the Secretary receives notice from the applicant under the i) the inactive ingredients of the drug are unsafe for use previous application of the first commercial marketing of the drug under the cribed, recommended, or suggested in the labeling pro- previous application, or i) the composition of the drug is unsafe under such (II) the date of a decision of a court in an action described in clause (iii) type or quantity of inactive ingredients included or the holding the patent which is the subject of the certification to be invalid or not ive ingredients are included; infringed, ubsection (c) of this section of the listed drug referred to whichever is earlier. this subsection has been withdrawn or suspended for first sentence of subsection (e) of this section, the (C) If the Secretary decides to disapprove an application, the Secretary shall give the notice of opportunity for hearing to withdraw approval of applicant notice of an opportunity for a hearing before the Secretary on the question of :ction (c) of this section for grounds described in the first whether such application is approvable. If the applicant elects to accept the opportunity of this section, the approval under this subsection of the for hearing by written request within thirty days after such notice, such hearing shall he application under this subsection has been withdrawn commence not more than ninety days after the expiration of such thirty days unless the raph (5), or the Secretary has determined that the listed Secretary and the applicant otherwise agree. Any such hearing shall thereafter be from sale for safety or effectiveness reasons; conducted on an expedited basis and the Secretary's order thereon shall be issued within ninety days after the date fixed by the Secretary for filing final briefs. not meet any other requirement of paragraph (2)(A); or ains an untrue statement of material fact. (D)(i) If an application (other than an abbreviated new drug application) submitted under subsection (b) of this section for a drug, no active ingredient (including any ester and eighty days of the initial receipt of an application or salt of the active ingredient) of which has been approved in any other application such additional period as may be agreed upon by the under subsection (b) of this section, was approved during the period beginning January e Secretary shall approve or disapprove the application. 1, 1982, and ending on September 24, 1984, the Secretary may not make the approval of lication submitted under paragraph (2) shall be made an application submitted under this subsection which refers to the drug for which the date determined under the following: subsection (b) application was submitted effective before the expiration of ten years from made a certification described in subclause (I) or (II) of the date of the approval of the application under subsection (b) of this section. both such subclauses, the approval may be made effective (ii) If an application submitted under subsection (b) of this section for a drug, no active ingredient (including any ester or salt of the active ingredient) of which has been e a certification described in subclause (III) of paragraph approved in any other application under subsection (b) of this section, is approved after y be made effective on the date certified under subclause September 24, 1984, no application may be submitted under this subsection which refers to the drug for which the subsection (b) application was submitted before the expiration ude a certification described in subclause (IV) of para- of five years from the date of the approval of the application under subsection (b) of this val shall be made effective immediately unless an action section, except that such an application may be submitted under this subsection after the nt of a patent which is the subject of the certification expiration of four years from the date of the approval of the subsection (b) application if orty-five days from the date the notice provided under it contains a certification of patent invalidity or noninfringement described in subclause ved. If such an action is brought before the expiration of (IV) of paragraph (2)(A)(vii). The approval of such an application shall be made all be made effective upon the expiration of the thirty- effective in accordance with subparagraph (B) except that, if an action for patent n the date of the receipt of the notice provided under infringement is commenced during the one-year period beginning forty-eight months shorter or longer period as the court may order because after the date of the approval of the subsection (b) application, the thirty-month period failed to reasonably cooperate in expediting the action. referred to in subparagraph (B)(iii) shall be extended by such amount of time (if any) which is required for seven and one-half years to have elapsed from the date of approval iration of such period the court decides that such patent of the subsection (b) application. ged, the approval shall be made effective on the date of (iii) If an application submitted under subsection (b) of this section for a drug, which includes an active ingredient (including any ester or salt of the active ingredient) that piration of such period the court decides that such patent has been approved in another application approved under subsection (b) of this section, e approval shall be made effective on such date as the is approved after September 24, 1984, and if such application contains reports of new ction 271(e)(4)(A) of Title 35 or clinical investigations (other than bioavailability studies) essential to the approval of the application and conducted or sponsored by the applicant, the Secretary may not make expiration of such period the court grants a preliminary the approval of an application submitted under this subsection for the conditions of the applicant from engaging in the commercial manufac- approval of such drug in the subsection (b) application effective before the expiration of ig until the court decides the issues of patent validity and three years from the date of the approval of the application under subsection (b) of this the court decides that such patent is invalid or not al shall be made effective on the date of such court section for such drug. (iv) If a supplement to an application approved under subsection (b) of this section is h of the parties shall reasonably cooperate in expediting approved after September 24, 1984, and the supplement contains reports of new clinical expiration of forty-five days from the date the notice investigations (other than bioavailability studies) essential to the approval of the h (2)(B)(i) is received, no action may be brought under supplement and conducted or sponsored by the person submitting the supplement, the '8 for a declaratory judgment with respect to the patent. Secretary may not make the approval of an application submitted under this subsection nder section 2201 shall be brought in the judicial district for a change approved in the supplement effective before the expiration of three years has its principal place of business or a regular and from the date of the approval of the supplement under subsection (b) of this section. usiness. (v) If an application (or supplement to an application) submitted under subsection (b) contains a certification described in subclause (IV) of of this section for a drug, which includes an active ingredient (including any ester or salt is for a drug for which a previous application has been of the active ingredient) that has been approved in another application under subsection ection continuing such a certification. the application shall (b) of this section, was approved during the period beginning January 1, 1982, and lier than one hundred and eighty days after- ending on September 24, 1984, the Secretary may not make the approval of an 182 183 21 § 355 FOOD AND DRUGS FOOD AND DRUGS application submitted under this subsection which refers to the drug for which the (ii) the extent of absorp: subsection (b) application was submitted or which refers to a change approved in a difference from the extent of supplement to the subsection (b) application effective before the expiration of two years at the same molar dose of the from September 24, 1984. tal conditions in either a sing (5) If a drug approved under this subsection refers in its approved application to a the listed drug in the rate of a drug the approval of which was withdrawn or suspended for grounds described in the its proposed labeling, is not e first sentence of subsection (e) of this section or was withdrawn or suspended under this concentrations on chronic use paragraph or which, as determined by the Secretary, has been withdrawn from sale for drug. safety or effectiveness reasons, the approval of the drug under this subsection shall be (8) The Secretary shall, with res: withdrawn or suspended- subsection, maintain a record of- (A) for the same period as the withdrawal or suspension under subsection (e) of this section or this paragraph, or (A) the name of the applicant, (B) if the listed drug has been withdrawn from sale, for the period of withdrawal (B) the name of the drug cove: from sale or, if earlier, the period ending on the date the Secretary determines that (C) the name of each person the withdrawal from sale is not for safety or effectiveness reasons. application was assigned and the (6)(A)(i) Within sixty days of September 24, 1984, the Secretary shall publish and (D) the name of each person make available to the public- application was assigned and the (I) a list in alphabetical order of the official and proprietary name of each drug which has been approved for safety and effectiveness under subsection (c) of this The information the Secretary is requir section before September 24, 1984; to an application submitted under this after the approval of such application. (II) the date of approval if the drug is approved after 1981 and the number of the application which was approved; and (k) Records and reports; required info: (III) whether in vitro or in vivo bioequivalence studies, or both such studies, are required for applications filed under this subsection which will refer to the drug (1) In the case of any drug for published. subsection (b) or (j) of this section is i: such records, and make such report (ii) Every thirty days after the publication of the first list under clause (i) the experience and other data or inform Secretary shall revise the list to include each drug which has been approved for safety and effectiveness under subsection (c) of this section or approved under this subsection applicant with respect to such drug, a during the thirty-day period. order with respect to such applicatio records and reports are necessary in (iii) When patent information submitted under subsection (b) or (c) of this section facilitate a determination, whether the respecting a drug included on the list is to be published by the Secretary, the Secretary of this section. Regulations and 0 shall, in revisions made under clause (ii), include such information for such drug. subsection (i) of this section shall ha (B) A drug approved for safety and effectiveness under subsection (c) of this section medical profession and the interests 0 or approved under this subsection shall, for purposes of this subsection. be considered to deems it to be appropriate, for the ex. have been published under subparagraph (A) on the date of its approval or September such regulations or orders are applic: 24, 1984, whichever is later. obtained by the Secretary. (C) If the approval of a drug was withdrawn or suspended for grounds described in (2) Every person required under th the first sentence of subsection (e) of this section or was withdrawn or suspended under charge or custody thereof, shall, upon paragraph (5) or if the Secretary determines that a drug has been withdrawn from sale the Secretary, permit such officer or E for safety or effectiveness reasons, it may not be published in the list under subpara- and copy and verify such records. graph (A) or, if the withdrawal or suspension occurred after its publication in such list, it shall be immediately removed from such list- (1) Public disclosure of safety and effect (i) for the same period as the withdrawal or suspension under subsection (e) of Safety and effectiveness data anc this section or paragraph (5), or application under subsection (b) of thi (ii) if the listed drug has been withdrawn from sale, for the period of withdrawal been disclosed to the public shall be I from sale or, if earlier, the period ending on the date the Secretary determines that extraordinary circumstances are show the withdrawal from sale is not for safety or effectiveness reasons. (1) if no work is being or will A notice of the removal shall be published in the Federal Register. (2) if the Secretary has determ (7) For purposes of this subsection: legal appeals have been exhauste (A) The term "bioavailability" means the rate and extent to which the active ingredient or therapeutic ingredient is absorbed from a drug and becomes available (3) if approval of the applicatio: at the site of drug action. and all legal appeals have been e (B) A drug shall be considered to be bioequivalent to a listed drug if (4) if the Secretary has dete. (i) the rate and extent of absorption of the drug do not show a significant (5) upon the effective date of t difference from the rate and extent of absorption of the listed drug when tion (j) of this section which refe: administered at the same molar dose of the therapeutic ingredient under approval of an application under similar experimental conditions in either a single dose or multiple doses: or drug could be made effective if S 184 FOOD AND DRUGS FOOD AND DRUGS 21 $ 355 section which refers to the drug for which the (ii) the extent of absorption of the drug does not show a significant itted or which refers to a change approved in a difference from the extent of absorption of the listed drug when administered lication effective before the expiration of two years at the same molar dose of the therapeutic ingredient under similar experimen- tal conditions in either a single dose or multiple doses and the difference from subsection refers in its approved application to a the listed drug in the rate of absorption of the drug is intentional, is reflected in drawn or suspended for grounds described in the its proposed labeling, is not essential to the attainment of effective body drug section or was withdrawn or suspended under this concentrations on chronic use, and is considered medically insignificant for the y the Secretary, has been withdrawn from sale for drug. pproval of the drug under this subsection shall be (8) The Secretary shall, with respect to each application submitted under this subsection, maintain a record of- withdrawal or suspension under subsection (e) of (A) the name of the applicant, r 1 withdrawn from sale, for the period of withdrawal (B) the name of the drug covered by the application, 1 ending on the date the Secretary determines that (C) the name of each person to whom the review of the chemistry of the for safety or effectiveness reasons. application was assigned and the date of such assignment, and tember 24. 1984, the Secretary shall publish and (D) the name of each person to whom the bioequivalence review for such application was assigned and the date of such assignment. of the official and proprietary name of each drug fety and effectiveness under subsection (c) of this The information the Secretary is required to maintain under this paragraph with respect to an application submitted under this subsection shall be made available to the public 84; after the approval of such application. : drug is approved after 1981 and the number of the and (k) Records and reports; required information; regulations and orders; access to records vo bioequivalence studies, or both such studies, are inder this subsection which will refer to the drug (1) In the case of any drug for which an approval of an application filed under subsection (b) or (j) of this section is in effect, the applicant shall establish and maintain such records. and make such reports to the Secretary, of data relating to clinical publication of the first list under clause (i) the experience and other data or information, received or otherwise obtained by such lude each drug which has been approved for safety applicant with respect to such drug, as the Secretary may by general regulation, or by c) of this section or approved under this subsection order with respect to such application, prescribe on the basis of a finding that such records and reports are necessary in order to enable the Secretary to determine, or bmitted under subsection (b) or (c) of this section facilitate a determination, whether there is or may be ground for invoking subsection (e) -t is to be published by the Secretary, the Secretary of this section. Regulations and orders issued under this subsection and under use (ii), include such information for such drug. subsection (i) of this section shall have due regard for the professional ethics of the nd effectiveness under subsection (c) of this section medical profession and the interests of patients and shall provide, where the Secretary all, for purposes of this subsection. be considered to deems it to be appropriate, for the examination, upon request, by the persons to whom graph (A) on the date of its approval or September such regulations or orders are applicable, of similar information received or otherwise obtained by the Secretary. S withdrawn or suspended for grounds described in (2) Every person required under this section to maintain records, and every person in of this section or was withdrawn or suspended under charge or custody thereof, shall, upon request of an officer or employee designated by termines that a drug has been withdrawn from sale the Secretary, permit such officer or employee at all reasonable times to have access to it may not be published in the list under subpara- and copy and verify such records. aspension occurred after its publication in such list, it 1 such list- (I) Public disclosure of safety and effectiveness data he withdrawal or suspension under subsection (e) of Safety and effectiveness data and information which has been submitted in an or application under subsection (b) of this section for a drug and which has not previously en withdrawn from sale, for the period of withdrawal been disclosed to the public shall be made available to the public, upon request, unless od ending on the date the Secretary determines that extraordinary circumstances are shown- it for safety or effectiveness reasons. (1) if no work is being or will be undertaken to have the application approved, iblished in the Federal Register. (2) if the Secretary has determined that the application is not approvable and all ion: legal appeais have been exhausted, ty" means the rate and extent to which the active dient is absorbed from a drug and becomes available (3) if approval of the application under subsection (c) of this section is withdrawn and all legal appeals have been exhausted, ered to be bioequivalent to a listed drug if- (4) if the Secretary has determined that such drug is not a new drug, or : of absorption of the drug do not show a significant (5) upon the effective date of the approval of the first application under subsec- and extent of absorption of the listed drug when tion (j) of this section which refers to such drug or upon the date upon which the ne molar dose of the therapeutic ingredient under approval of an application under subsection (j) of this section which refers to such ditions in either a single dose or multiple doses; or drug could be made effective if such an application had been submitted. 184 185 21 § 355 FOOD AND DRUGS FOOD AND DRUGS (m) "Patent" defined 96-88, Title VI, Oct. 17, 1979, 93 Stat. 696 For purposes of this section, the term "patent" means a patent issued by the Patent out as a note under section 3401 of Titl and Trademark Office of the Department of Commerce. Education, deemed to refer and apply to Department of Health and Human Service (As amended Aug. 16, 1972. Pub.L. 92-387, $ 4(d), 86 Stat. 562; Sept. 24, 1984. Pub.L. 98-417, Title the Secretary of Health and Human Serv I, §§ 101, 102(a)-(b)(5). 103, 104. 98 Stat. 1585. 1592, 1593, 1597; May 13, 1992, Pub.L. 102-282, § 5, respectively, except to the extent such refer- 106 Stat. 161; Aug. 13, 1993. Pub.L. 103-80, § 3(n), 107 Stat. 777.) is to a function or office transferred to Secretary of Education or the Departmer HISTORICAL AND STATUTORY NOTES Education under Pub.L. 96-88, Title III, §§ 1993 Amendments to 307, Oct. 17 1979, 93 Stat. 677 to 681. scribed by subsec. (b) of this section. Former section 3441 to 3447 and 3508 of Title 20. Subsec. (j)(6)(A)(ii). Pub.L. 103-80, cl. (6) was redesignated (7). § 3(n)(1)(A), corrected a typographical error in Subsec. (d)(7). Pub.L. 98-417, § 102(a)(3)(A), Effective Date of 1984 Amendment the original by substituting "Secretary" for redesignated former cl. (6) as (7). "Secretry". Section 105 of Pub.L. 98-417 provided Subsec. (e). Pub.L. 98-417, $ 102(a)(3)(B), Subsec. (j)(6)(A)(iii). Pub.L. 103-80. added, in the first sentence covering the "(a) The Secretary of Health and Hu § 3(n)(1)(B). inserted a comma after "published grounds for withdrawal of approval by the Sec- Services shall promulgate, in accordance by the Secretary". retary, a new cl. (4) relating to the failure to file the notice and comment requirements of se Subsec. (k)(1). Pub.L. 103-80, § 3(n)(2), the patent information prescribed by subsec. (c) 553 of title 5, United States Code [section 5 struck out *: Provided, however. That regula- of this section within 30 days after the receipt of Title 5, Government Organization and Emp tions" and inserted in lieu thereof a period and written notice from the Secretary specifying the ees), such regulations as may be necessary "Regulations". failure to file such information, and redesignated the administration of section 505 of the Fec the former cl. (4) as (5). Food, Drug, and Cosmetic Act [this section 1992 Amendments Pub.L. 98-417, § 102(b)(3). inserted. in the amended by sections 101, 102, and 103 of Subsec. (j)(8). Pub.L. 102-282. § 5, added Act [enacting subsec. (j) of this section provisions of the second sentence preceding cl. par. (8). amending subsecs. (a) to (e) and (k)(1) of (1) of the enumeration of clauses covering the section and section 360cc(a) and (b) of this t 1984 Amendment grounds for withdrawal of approval by the Sec- within one year of the date of enactment of retary. the phrase "submitted under subsection Subsec. (a). Pub.L. 98-417, § 102(b)(1), add- (b) or (j) of this section" after "withdraw the Act [Sept. 24, 1984]. ed "or (j)" following "pursuant to subsection approval of an application". "(b) During the period beginning sixty (b)". Pub.L. 98-417, § 102(b)(4), substituted, in cl. after the date of the enactment of this Act [S Subsec. (b)(1). Pub.L. 98-417. § 103(a), des- (1) of the second sentence covering the grounds 24, 1984], and ending on the date regulat ignated the existing provisions of subsec. (b) as for withdrawal of approval by the Secretary, the promulgated under subsection (a) take ef par. (1) thereof and redesignated existing cls. (1) phrase "under subsection (k) of this section or to abbreviated new drug applications may be through (6) of par. (1) as so redesignated as cls. comply with the notice requirements of section mitted in accordance with the provisions of (A) through (F) thereof, respectively. 360(k)(2) of this title" for "under subsection (j) tion 314.2 of title 21 of the Code of Fed Pub.L. 98-417, $ 102(a)(1), added requirement of this section or to comply with the notice Regulations and shall be considered as suit that the applicant file with the application the requirements of section 360(j)(2) of this title". for any drug which has been approved for BE patent number and the expiration date of any Subsec. (j). Pub.L. 98-417. § 101, added sub- and effectiveness under section 505(c) of patent which claims the drug for which the Federal Food, Drug, and Cosmetic Act [sui sec. (j). Former subsec. (j) was redesignated applicant submitted the application or which (k). (c) of this section) before the date of the en claims a method of using such drug and with respect to which a claim of patent infringement Subsec. (k). Pub.L. 98-417, § 101, redesig- CROS: could reasonably be asserted if a person not nated former subsec. (j) as (k). Patents. extension of patent term, see sec licensed by the owner engaged in the manufac- Subsec. (k)(1). Pub.L. 98-417, § 102(b)(5), 156 of Title 35, Patents. ture. use. or sale of the drug. that the applicant substituted "under subsection (b) or (j) of this amend the application to include such informa- section" for "pursuant to this section". FEDERAL PRA tion if an application is filed under this subsec- Subsecs. (l), (m). Pub.L. 98-417, § 104, add- tion for a drug and a patent which claims such ed subsecs. (l) and (m). Review of administrative decisions in court drug or a method of using such drug is issued appeals, see Wright, Miller, Cooper & Gr after the filing date but before approval of the 1972 Amendment man: Jurisdiction § 3941. application. and that, upon approval of the appli- Subsec. (e). Pub.L. 92-387 inserted "or to cation, the Secretary publish the information comply with the notice requirements of section WESTS FEDE] submitted. 360(j) (2)" in clause (1) of the second sentence Application for use of new drug, see § 3 Subsec. (b)(2), (3). Pub.L. 98-417, § 103(a), relating to the maintenance of records. added pars. (2) and (3). Change of Name CODE OF FE Subsec. (c)(1). Pub.L. 98-417, § 102(a)(2), The Department of Health, Education, and Formal evidentiary public hearing, see designated the existing provisions of subsec. (c) Welfare was redesignated the Department of CFR 12.1 et seq. as par. (1) thereof and in par. (1) as 80 designat- Health and Human Services, and the Secretary New animal drugs, see 21 CFR 510.3. ed redesignated former pars. (1) and (2) as of Health, Education. and Welfare or any other subpars. (A) and (B), respectively. official of the Department of Health, Education LAW REVII Pub.L. 98-417, § 102(b)(2), substituted "sub- and Welfare was redesignated the Secretary or A survey of law regarding the liability section (b) of this section" for "this subsection". official. as appropriate, of Health and Human manufacturers and sellers of drug products Subsec. (c)(2). Pub.L. 98-417, § 102(a)(2). Services, with any reference to the Department of Health. Education. and Welfare, the Secre- medical devices. Bryan J. Maedgen and She added par. (2). tary of Health, Education, and Welfare, or any Lynn McCall, 18 St. Mary's L.J. 395 (19 Subsec. (c)(3). Pub.L. 98-417, § 103(b). add- ed par. (3). official of the Department of Health, Education, Brother can you spare a drug: Should and Welfare, in any law, rule, regulation. certifi- experimental drug distribution standards Subsec. (d)(6). Pub.L. 98-417, § 102(a)(3)(A), cate, directive, instruction. or other official pa- modified in response to the needs of pers added cl. (6) relating to the failure of the appli- per in force on the effective date of Pub.L. with Aids? 19 Hofstra L.Rev. 191 (1990). cation to contain the patent information pre- 96-88, as prescribed by section 601 of Pub.L. 186 9 Ch. 9 FOOD, DRUG, AND COSMETIC ACT 21 § 355 ilm- cer- tions for potentially harmful drug with- dicts is not necessary. Dugan Drug 903. out authorization by prescribing physician Stores. Inc. V. I'. S., C.A.Tex.1964. 326 F. was immaterial since consistency in yer. 2d 835. ha tion ith. § 354. Repealed. Pub.L. 86-618, Title I, § 103(a) (2), July 12, 1960, 74 Stat. 398 tain oxic heir Historical Note S. Section. Act June 25. 1938. C. 675. $ 504. Effective Date of Repeal. Repeal of 52 Stat. 1052. required the Secretary to section effective. subject to the provisions re- promulgate regulations for the listing of of section 203 of Pub.L. 86-618. on July hor- coal-tar colors for drugs and is covered 12. 1960. see section 202 of Pub.L. SG-618. by section 376 of this title by set out as a note under section 376 of ion, this title. the 310 § 355. New drugs-Necessity of effective approval of appli- ens- tab- cation rim- sity (a) No person shall introduce or deliver for introduction into inter- tion state commerce any new drug. unless an approval of an application iven filed pursuant to subsection (b) of this section is effective with re- time spect to such drug. tent in ony Filing application; contents and ful. (b) Any person may file with the Secretary an application with re- :F. 368 spect to any drug subject to the provisions of subsection (a) of this ned section. Such person shall submit to the Secretary as a part of the ..). application (1) full reports of investigations which have been made to ons- show whether or not such drug is safe for use and whether such drug tab- is effective in use; (2) a full list of the articles used as components rap- of such drug: (3) a full statement of the composition of such drug: "no- (4) a full description of the methods used in, and the facilities and tion. controls used for, the manufacture, processing, and packing of such the drug; (5) such samples of such drug and of the articles used as com- tate .Ga. ponents thereof as the Secretary may require; and (6) specimens of 0 S. the labeling proposed to be used for such drug. Period for approval of application; period for, notice, and expedition of hearing; period for issuance of order rap- phe- (c) Within one hundred and eighty days after the filing of an ap- tion plication under this subsection, or such additional period as may be gton agreed upon by the Secretary and the applicant. the Secretary shall ei- ther— (1) approve the application if he then finds that none of the and grounds for denying approval specified in subsection (d) of this rip- section applies, or 387 21 § 355 FOOD AND DRUGS Ch. 9 Ch. 9 (2) give the applicant notice of an opportunity for a hearing effect it pt before the Secretary under subsection (d) of this section on the prescribed. question whether such application is approvable. If the applicant beling the elects to accept the opportunity for hearing by written request within thirty days after such notice, such hearing shall commence Withdr: not more than ninety days after the expiration of such thirty days unless the Secretary and the applicant otherwise agree. Any (e) The such hearing shall thereafter be conducted on an expedited basis ing to the and the Secretary's order thereon shall be issued within ninety to any dru days after the date fixed by the Secretary for filing final briefs. or other e is unsafe Grounds for refusing application: approval of application: the applic. "substantial evidence" defined rience, no: (d) If the Secretary finds, after due notice to the applicant in ac- tary until cordance with subsection (c) of this section and giving him an oppor- ods, or te tunity for a hearing, in accordance with said subsection, that (1) the applicatio investigations, reports of which are required to be submitted to the ble to the Secretary pursuant to subsection (b) of this section, do not include ad- such drug equate tests by all methods reasonably applicable to show whether or upon the not such drug is safe for use under the conditions prescribed, recom- basis of n mended. or suggested in the proposed labeling thereof; (2) the results ated toge! of such tests show that such drug is unsafe for use under such condi- was appr tions or do not show that such drug is safe for use under such condi- drug will tions; (3) the methods used in, and the facilities and controls used the condit for, the manufacture, processing, and packing of such drug are inade- beling the quate to preserve its identity, strength. quality, and purity; (4) upon ment of a the basis of the information submitted to him as part of the applica- sence the tion, or upon the basis of any other information before him with re- hazard to spect to such drug, he has insufficient information to determine plication whether such drug is safe for use under such conditions; or (5) eval- tion and uated on the basis of the information submitted to him as part of the ing under application and any other information before him with respect to such to susper. drug, there is a lack of substantial evidence that the drug will have the Secretary effect it purports or is represented to have under the conditions of use the appli prescribed. recommended, or suggested in the proposed labeling there- any drug of or (6) based on a fair evaluation of all material facts, such label- cant has ing is false or misleading in any particular; he shall issue an order or has re refusing to approve the application. If, after such notice and opportu- make req nity for hearing, the Secretary finds that clauses (1) through (6) do subsectio: not apply, he shall issue an order approving the application. As used access to in this subsection and subsection (e) of this section, the term "sub- paragrap stantial evidence" means evidence consisting of adequate and well-con- formation trolled investigations, including clinical investigations, by experts when the qualified by scientific training and experience to evaluate the effec- ties and tiveness of the drug involved, on the basis of which it could fairly and such dru responsibly be concluded by such experts that the drug will have the quality. : 388 Ch. 9 Ch. 9 FOOD. DRUG. AND COSMETIC ACT 21 § 355 for a hearing effect it purports or is represented to have under the conditions of use section on the prescribed. recommended. or suggested in the labeling or proposed la- f the applicant beling thereof. ritten request hall commence Withdrawal of approval: grounds: immediate suspension upon finding of such thirty imminent hazard to public health se agree. Any (e) The Secretary shall. after due notice and opportunity for hear- xpedited basis ing to the applicant. withdraw approval of an application with respect within ninety to any drug under this section if the Secretary finds (1) that clinical g final briefs. or other experience. tests. or other scientific data show that such drug is unsafe for use under the conditions of use upon the basis of which ation: the application was approved; (2) that new evidence of clinical expe- rience, not contained in such application or not available to the Secre- plicant in ac- tary until after such application was approved, or tests by new meth- him an oppor- ods. or tests by methods not deemed reasonably applicable when such that (1) the application was approved. evaluated together with the evidence availa- mitted to the ble to the Secretary when the application was approved. shows that not include ad- such drug is not shown to be safe for use under the conditions of use W whether or upon the basis of which the application was approved; or (3) on the cribed, recom- basis of new information before him with respect to such drug, evalu- 2) the results ated together with the evidence available to him when the application er such condi- was approved. that there is a lack of substantial evidence that the r such condi- drug will have the effect it purports or is represented to have under controls used the conditions of use prescribed. recommended. or suggested in the la- ug are inade- beling thereof: or (4) that the application contains any untrue state- :ty; (4) upon ment of a material fact: Provided, That if the Secretary (or in his ab- f the applica- sence the officer acting as Secretary) finds that there is an imminent him with re- hazard to the public health. he may suspend the approval of such ap- to determine plication immediately. and give the applicant prompt notice of his ac- or (5) eval- tion and afford the applicant the opportunity for an expedited hear- :S part of the ing under this subsection: but the authority conferred by this proviso spect to such to suspend the approval of an application shall not be delegated. The will have the Secretary may also. after due notice and opportunity for hearing to litions of use the applicant, withdraw the approval of an application with respect to beling there- any drug under this section if the Secretary finds (1) that the appli- S, such label- cant has failed to establish a system for maintaining required records, sue an order or has repeatedly or deliberately failed to maintain such records or to and opportu- make required reports. in accordance with a regulation or order under rough (6) do subsection (j) of this section, or the applicant has refused to permit on. As used access to, or copying or verification of. such records as required by : term "sub- paragraph (2) of such subsection; or (2) that on the basis of new in- and well-con- formation before him, evaluated together with the evidence before him by experts when the application was approved, the methods used in. or the facili- t.e the effec- ties and controls used for. the manufacture. processing, and packing of Id fairly and such drug are inadequate to assure and preserve its identity, strength, vill have the quality. and purity and were not made adequate within a reasonable 389 21 § 355 FOOD AND DRUGS Ch. 9 Ch. time after receipt of written notice from the Secretary specifying the addu matter complained of ; or (3) that on the basis of new information be- court fore him, evaluated together with the evidence before him when the reaso application was approved, the labeling of such drug, based on a fair ing t evaluation of all material facts, is false or misleading in any particu- to be lar and was not corrected within a reasonable time after receipt of in su written notice from the Secretary specifying the matter complained of. may Any order under this subsection shall state the findings upon which it facts is based. with tial Revocation of order refusing, withdrawing or suspending the S approval of application firm: (f) Whenever the Secretary finds that the facts so require, he shall subje revoke any previous order under subsection (d) or (e) of this section tiora refusing, withdrawing, or suspending approval of an application and comr shall approve such application or reinstate such approval, as may be speci appropriate. the Service of orders (g) Orders of the Secretary issued under this section shall be served (1) in person by any officer or employee of the Department (i) designated by the Secretary or (2) by mailing the order by registered the mail or by certified mail addressed to the applicant or respondent at tend his last-known address in the records of the Secretary. train drug. Appeal from order amor (h) An appeal may be taken by the applicant from an order of the provi Secretary refusing or withdrawing approval of an application under this section. Such appeal shall be taken by filing in the United States court of appeals for the circuit wherein such applicant resides or has his principal place of business, or in the United States Court of Ap- peals for the District of Columbia Circuit, within sixty days after the entry of such order, a written petition praying that the order of the Secretary be set aside. A copy of such petition shall be forthwith transmitted by the clerk of the court to the Secretary, or any officer designated by him for that purpose, and thereupon the Secretary shall certify and file in the court the record upon which the order com- plained of was entered, as provided in section 2112 of Title 28. Upon the filing of such petition such court shall have exclusive jurisdiction to affirm or set aside such order, except that until the filing of the record the Secretary may modify or set aside his order. No objection to the order of the Secretary shall be considered by the court unless such objection shall have been urged before the Secretary or unless there were reasonable grounds for failure SO to do. The finding of the Secretary as to the facts, if supported by substantial evidence, shall be conclusive. If any person shall apply to the court for leave to 390 Ch. 9 Ch. 9 FOOD, DRUG, AND COSMETIC ACT 21 § 355 etary specifying the adduce additional evidence, and shall show to the satisfaction of the new information be- court that such additional evidence is material and that there were efore him when the reasonable grounds for failure to adduce such evidence in the proceed- rug, based on a fair ing before the Secretary, the court may order such additional evidence ding in any particu- to be taken before the Secretary and to be adduced upon the hearing ime after receipt of in such manner and upon such terms and conditions as to the court hatter complained of. may seem proper. The Secretary may modify his findings as to the ndings upon which it facts by reason of the additional evidence so taken, and he shall file with the court such modified findings which, if supported by substan- tial evidence, shall be conclusive, and his recommendation, if any, for suspending the setting aside of the original order. The judgment of the court af- firming or setting aside any such order of the Secretary shall be final, S so require, he shall subject to review by the Supreme Court of the United States upon cer- r (e) of this section tiorari or certification as provided in section 1254 of Title 28. The f an application and commencement of proceedings under this subsection shall not, unless approval, as may be specifically ordered by the court to the contrary, operate as a stay of the Secretary's order. his section shall be Exemptions of drugs for research: discretionary and mandatory conditions: direct reports to Secretary e of the Department (i) The Secretary shall promulgate regulations for exempting from e order by registered the operation of the foregoing subsections of this section drugs in- ant or respondent at tended solely for investigational use by experts qualified by scientific tary. training and experience to investigate the safety and effectiveness of drugs. Such regulations may, within the discretion of the Secretary, among other conditions relating to the protection of the public health, from an order of the provide for conditioning such exemption upon- an application under (1) the submission to the Secretary, before any clinical testing in the United States of a new drug is undertaken, of reports. by the manufacturer or licant resides or has the sponsor of the investigation of such drug, of preclinical tests States Court of Ap- (including tests on animals) of such drug adequate to justify the 1 sixty days after the proposed clinical testing; that the order of the in shall be forthwith (2) the manufacturer or the sponsor of the investigation of a retary, or any officer new drug proposed to be distributed to investigators for clinical on the Secretary shall testing obtaining a signed agreement from each of such investiga- which the order com- tors that patients to whom the drug is administered will be under 12 of Title 28. Upon his personal supervision. or under the supervision of investigators exclusive jurisdiction responsible to him. and that he will not supply such drug to any intil the filing of the other investigator. or to clinics, for administration to human order. No objection beings; and d by the court unless (3) the establishment and maintenance of such records, and the Secretary or unless making of such reports to the Secretary, by the manufacturer or do. The finding of the sponsor of the investigation of such drug, of data (including substantial evidence. but not limited to analytical reports by investigators) obtained as the court for leave to the result of such investigational use of such drug, as the Secre- 391 21 § 355 FOOD AND DRUGS Ch. 9 Ch. 9 F tary finds will enable him to evaluate the safety and effectiveness 631; June 11. of such drug in the event of the filing of an application pursuant 1962, Pub.L. 8 to subsection (b) of this section. (2), 76 Stat. 78 Such regulations shall provide that such exemption shall be condi- tioned upon the manufacturer, or the sponsor of the investigation, re- quiring that experts using such drugs for investigational purposes 1962 Amendment 87-781, § 104(a). certify to such manufacturer or sponsor that they will inform any of" preceding "A human beings to whom such drugs, or any controls used in connec- Subsec. (b). l' tion therewith, are being administered, or their representatives, that inserted "and wh such drugs are being used for investigational purposes and will ob- fective in use" use." tain the consent of such human beings or their representatives, ex- cept where they deem it not feasible or, in their professional judg- Subsec. (c). P substituted provis ment, contrary to the best interests of such human beings. Nothing retary, within 18 in this subsection shall be construed to require any clinical investi- application, or su gator to submit directly to the Secretary reports on the investiga- the Secretary an upon, to either : tional use of drugs. if meeting the T (d) of this sectio portunity for h. Records and reports; required Information: regulations and orders: whether such AP acceKa 10 records and providing th (j) (1) In the case of any drug for which an approval of an appli- hearing in writi: hearing shall beL cation filed pursuant to this section is in effect. the applicant shall es- expiration of sa tablish and maintain such records, and make such reports to the Secre- Secretary and ap that such heari tary, of data relating to clinical experience and other data or informa- and that the Se tion, received or otherwise obtained by such applicant with respect to issued within 90 such drug. as the Secretary may by general regulation. or by order final briefs, for with respect to such application, prescribe on the basis of a finding application bee sixtieth day aft. that such records and reports are necessary in order to enable the Sec- prior thereto 11 retary to determine. or facilitate a determination. whether there is or the date by writ but not more th may be ground for invoking subsection (e) of this section: Provided, as the Secretar: however, That regulations and orders issued under this subsection and study and inves under subsection (i) of this section shall have due regard for the pro- Subsec. (d). fessional ethics of the medical profession and the interests of patients inserted referenc- and shall provide. where the Secretary deems it to be appropriate. for cls. (5) and (6). the examination. upon request, by the persons to whom such regula- notice and oppo: Secretary finds tions or orders are applicable, of similar information received or oth- apply, he shall erwise obtained by the Secretary. and defined "s' used in this sui (2) Every person required under this section to maintain records, of this section. and every person in charge or custody thereof, shall, upon request of Subsec. (e). an officer or employee designated by the Secretary, permit such offi- amended subsect other changes. d cer or employee at all reasonable times to have access to and copy and withdraw approv verify such records. by tests. other ence, or new evi June 25. 1938, c. 675, § 505, 52 Stat. 1052: 1940 Reorg. Plan No. IV, § ence not contain- 12, eff. June 30, 1940, 5 F.R. 2422. 54 Stat. 1237 June 25, 1948, c. available at the drug is shown 646, § 32(b), 62 Stat. 991; May 24, 1949, c. 139, § 127, 63 Stat. 107; basis of new inf 1953 Reorg. Plan No. 1, § 5, eff. Apr. 11. 1953, 18 F.R. 2053, 67 Stat. a lack of subst. 392 T. 21 U.S.C.A. UGS Ch. 9 Ch. 9 FOOD, DRUG, AND COSMETIC ACT 21 § 355 the safety and effectiveness 631; June 11, 1960, Pub.L. 86-507, § 1(18), 74 Stat. 201; Oct. 10, g of an application pursuant 1962, Pub.L. 87-781. Title I. §§ 102(b)-(d), 103(a), (b), 104(a)-(d) (2), 76 Stat. 781-783, 784. 785. h exemption shall be condi- nsor of the investigation, re- Historical Note for investigational purposes 1962 Amendment. Subsec. (a). Pub.L. drug has the effect it is represented to r that they will inform any 87-781. § 104(a). inserted "an approval have. and provided that if the Secretary. of" preceding "nn application." or acting Secretary. finds there is an im- my controls used in connec- minent hazard to public health, he may Subsec. (b). Pub.L. 87-781. § 102(b). or their representatives, that suspend approval immediately. notify the Inserted "and whether such drug is ef- applicant. and give him opportunity for tional purposes and will ob- fective in use" following "is safe for an expedited hearing. that the Secretary or their representatives. ex- use." may withdraw approval if the applicant ; in their professional judg- Subsec. (e). Pub.L. 87-781. § 104(b). fails to establish a system for maintain- uch human beings. Nothing substituted provisions requiring the Sec- ing required records. or has repeatedly retary, within 180 days after filing an or deliberately failed to maintain rec- require any clinical investi- application. or such additional period as ords and make reports, or has re- ry reports on the investiga- the Secretary and the applicant agree fused access to. or copying or verifica- tion of such records, or if the Secretary upon, to either approve the application, finds on new evidence that the methods. if meeting the requirements of subsec. facilities and controls in the manufac- (d) of this section, or give notice of op- turing. processing. and packing are in- portunity for hearing on question of on: regulations and orders: whether such application is approvable. adequate to assure and preserve the de drugs' identity, strength. quality and and providing that if applicant requests hearing in writing within 30 days. the purity, and were not made adequate hich an approval of an appli- hearing shall begin within 90 days after within a reasonable time after receipt effect. the applicant shall es- of written notice thereof. or finds on expiration of said 30 days. unless the ake such reports to the Secre- Secretary and applicant agree otherwise. new evidence, that the labeling is false or musleading and was not corrected ce and other data or informa- that such hearing shall be expedited. within a reasonable time after receipt and that the Secretary's order shall be uch applicant with respect to of written notice thereof. issued within 90 days after date for filing neral regulation. or by order final briefs, for provisions which had an Subsec. (f). Pub.L. ST-781. $ 104(c). be on the basis of a finding application become effective on the substituted provisions requiring the sixtieth day after filing thereof unless ary in order to enable the Sec- Secretary to revoke any previous order prior thereto the Secretary postponed under subsees, (1) or (e) of this section mination. whether there is or the date by written notice to such time, refusing. withdrawing. or suspending ap- e) of this section: Provided, but not more than 180 days after filing. proval of an application and to approve as the Secretary deemed necessary to ued under this subsection and such application or reinstate such ap- study and investigate the application. proval. for provisions which required have due regard for the pro- him to revoke an order refusing effective- Subsec. (d). Pub.L. ST-781. $ 102(c). and the interests of patients ness to an application. inserted references to subsec. (e). added eems it to be appropriate. for cls. (5) and (6), provided that if after Subsec. (h). Pub.L. ST-781. $ 104(d) ersons to whom such regula- notice and opportunity for hearing, the (1), (2). inserted "as provided in section Secretary finds that cls. (1)-(6) do not : information received or oth- 2112 of Title 28". and "except that until apply. he shall approve the application. the filing of the record the Secretary may and defined "substantial evidence" as modify or set aside his order". substi- used in this subsection and subsee. (e) futed "or withdrawing approval of an S section to maintain records. of this section. application under this section" for "to thereof, shall. upon request of Subsec. (e). Pub.L. 87-781, $ 102(d) permit the application to become effec- e Secretary, permit such offi- amended subsection generally. and among tive, or suspending the effectiveness of 0 have access to and copy and other changes. directed the Secretary to the application". "United States court withdraw approval of an application if of appeals for the circuit" for "district by tests. other scientific data or experi- court of the United States within any ence. or new evidence of clinical experi- district". "Court of Appeals for the Dis- 12: 1940 Reorg. Plan No. IV, § ence not contained in the application or trict of Columbia Circuit" for "District Stat. 1237; June 25, 1948, c. available at the time of its approval, the Court for the District of Columbia", drug is shown to be unsafe. or on the "transmitted by the clerk of the court 19, c. 139, § 127, 63 Stat. 107: basis of new information. there is shown to" for "served upon". and "by the Su- 1. 1953, 18 F.R. 2053, 67 Stat. a lack of substantial evidence that the preme Court of the United States upon T. 21 U.S.C.A. §§ 1-800-14 393 828 FEDERAL REPORTER, 2d SERIES GRINSPOON V. DRUG ENFORCEMENT ADMIN. 881 880 Cite as 828 F.2d 881 (1st Clr. 1987) take its meaning from the statute that is a balance between efforts to protect exist- likely condition when a pension fund seeks being amended-ERISA. And ERISA, for ing pension plan beneficiaries through a to recover against officers or shareholders Lester GRINSPOON, M.D., Petitioner, whatever reason, defines the word "em- short term strategy of imposing burdens personally, the corporation will enter into V. ployer" only for subchapter I.¹ Defining on current employer contributors and bankruptcy proceedings, thereby losing DRUG ENFORCEMENT its meaning for subchapter III is up to the through a long term strategy of encourag- control over which creditors receive pay- ADMINISTRATION, courts. Cf. Robinson v. C.I.R., 805 F.2d ing new employers to contribute to multi- ments. Respondent. 38, 40 (1st Cir.1986).² employer pension funds. See H.R. No. 96- Given the control corporations have over 869, 96th Cong., 2d Sess., reprinted in No. 86-2007. (3) This conclusion brings us back to payroll taxes and wages, personal liability 1980 U.S.Code Cong. & Admin.News at what the Trustee is really asking us to do: for those debts should rarely have actually United States Court of Appeals, 2918, 2919-20, 2935. Imposing personal to define the word "employer" to include assessed. The threat of personal liability First Circuit. liability for withdrawal payments would controlling shareholders and officers. We should be enough to induce the individuals hurt that long term strategy by discourag- who control corporations to prefer the IRS Heard March 3, 1987. decline, for the following reasons. ing controlling individuals from directing and employee creditors over other creditors Decided Sept. 18, 1987. First, as mentioned before, the principle their corporations to participate in multi- in times of financial difficulty. If not, the of limited liability for corporate debts is employer pension funds. individuals controlling the corporation ac- longstanding enough and important enough Withdrawal liability under the MPPAA is cept a known risk. Personal liability for Administrative Drug Enforcement Ad- to be considered a background norm, quite different than payroll taxes under the withdrawal payments, on the other hand, ministration issued final rule placing 3, 4- against which Congress may act of course, Social Security Act and minimum wage cannot be similarly avoided. This personal methylenedioxymethamphetamine into but which is controlling in the absence of Schedule I of Controlled Substances Act. payments under the Fair Labor Standards liability may well force corporations to such action. See Connors v. P & M Coal Act, two corporate debts for which control- more extreme efforts to avoid bankruptcy, Researcher on therapeutic use of substance Co., 801 F.2d at 1376. In deciding whether ling shareholders and officers can be held but any benefit is likely to be marginal, petitioned for review. The Court of Ap- Congress has acted to expand liability "fed- liable. See Donovan v. Agnew, 712 F.2d at since controlling shareholders can be ex- peals, Coffin, Circuit Judge, held that: (1) eral courts will look closely at the purpose 1511; United States v. McMullen, 516 F.2d pected to attempt to avoid bankruptcy gen- absence of FDA interstate marketing ap- of the federal statute to determine whether 917, 920 (7th Cir.1975) (26 U.S.C. § 7512 erally, in the hope of obtaining some return proval was not conclusive evidence that the statute places importance on the corpo- imposes liability for payroll taxes on person on their investment. Rather than a rarely substance had no currently accepted medi- rate form Town of Brookline v. with control over corporations affairs). exercised threat that induces a desired be- cal use or lacked accepted safety for use Gorsuch, 667 F.2d 215, 221 (1st Cir.1981) Payroll taxes and minimum wage payments havior, personal liability for withdrawal under medical supervision; (2) there was (citations omitted). The MPPAA does not are liabilities which a corporation can payments would be a routine accompani- sufficient evidence to support finding that on its face indicate any intention to treat choose to pay or not pay. A decision to ment to corporate bankruptcy proceedings. substance had high potential for abuse; corporate debts for withdrawal liability dif- forgo paying payroll taxes or wages is a This personal liability would discourage and (3) administrator was not required to ferent from any other corporate debts. conscious decision to prefer some creditors controlling shareholders and officers from consider evidence that placement of sub- The way that one could have expected Con- over the government or the corporation's directing their corporations to contribute to stance into Schedule I would strongly dis- gress to make such an intention felt was employees. Corporations do not have the multi-employer pension plans, thereby mak- courage medical research on substance. through a definition of the word "employ- same control over withdrawal liability pay- ing it less likely that their employees will Rule vacated and remanded. er." Yet Congress did not define the word ments, especially in the context in which receive pension benefits. In the long run, in the MPPAA. Nor did Congress provide shareholder and officer liability is most personal liability would hurt even those an applicable definition in ERISA. likely to be relevant: bankruptcy. With- employees who are already beneficiaries of 1. Drugs and Narcotics -46 Furthermore, the purposes of the drawal liability is not assessed until an multi-employer pension plans, because the Absence of interstate marketing ap- MPPAA, as described in the legislative his- employer "withdraws" from the pension vitality of those plans depends on new em- proval of substance by Federal Drug Ad- tory of that act, would not be served by an plan, by ceasing to do business for in- ministration is not conclusive evidence that ployers contributing to them. See House extension of personal liability for corporate stance. If the liabilities of the employer Report, 1980 U.S.Code Cong. & Admin. substance has no currently accepted medi- withdrawal payments. The Act represents corporation exceed its assets, which is the News at 2919-20, 2935. cal use and lacks accepted safety for use under medical supervision for purposes of 1. In Nachman Corp. V. Pension Benefit Guar. cers or shareholders, a question which has occa- The decision of the district court is af- determining whether substance should be Corp., 446 U.S. 359, 370 n. 14, 100 S.C. 1723, sioned considerable litigation, and difference of opinion. Compare, e.g., Solomon V. Klein, 770 firmed. 1731 n. 14, 64 L.Ed.2d 354 (1980), the Supreme placed in Schedule I under Controlled Sub- Court noted that Congress made some Title I F.2d 352, 354 (3d 1985) (controlling share. stances Act. Comprehensive Drug Abuse (subchapter I in the Code) definitions applicable holder and officer not an "employer") with, e.g., Prevention and Control Act of 1970, to Title IV (part of subchapter III in the Code), Mass. State Carpenters Pension Fund V. Atlantic see, e.g., 29 U.S.C. § 1321(a)(1). "This specific § 202(b)(1), as amended, 21 U.S.C.A. Diving Co., Inc., 635 F.Supp. 9, 13-14 (D.Mass. KEY NUMBER SYSTEM incorporation suggests that Title I definitions do 1984) (controlling shareholder or officer may be § 812(b)(1). not apply elsewhere in the Act of their own "employer"). We reserve this question for a force Id. case in which it makes a difference in the out- 2. Drugs and Narcotics -46 2. We do not reach the question whether the come. Finding that 3, 4-methylenedioxymeth- subchapter I definition includes controlling offi- amphetamine had "high" potential for 882 828 FEDERAL REPORTER, 2d SERIES GRINSPOON V. DRUG ENFORCEMENT ADMIN. 883 Cite as 828 F.2d 881 (1st Clr. 1987) Drug Section, Dennis F. Hoffman, Chief for "accepted safety for use under Schedule I criteria listed in section 812(b)(1) abuse was not arbitrary and capricious, where administrator of Drug Enforcement Counsel, Drug Enforcement Admin., Ste- medical supervision" in 21 U.S.C. and concluded that (1) MDMA has a high Administration considered close structural phen E. Stone, Associate Chief Counsel, § 812(b)(1). The other three reasons con- potential for abuse; (2) MDMA has no and pharmacological similarity between Drug Enforcement Admin., Washington, tained in Dr. Grinspoon's petition challenge known legitimate medical use for treat- substance and other substances which had D.C., and Charlotte A. Johnson, were on the scheduling determination as arbitrary ment in the United States; and (3) there is already been found to have high potential brief, for respondent. and capricious because (a) the Administra- a lack of accepted safety for the use of tor's determination that MDMA had a for abuse and placed in Schedule I, as well MDMA under medical supervision. Based as studies which suggested that substance Before COFFIN and TORRUELLA, "high" potential for abuse was flawed by upon these findings, the DEA recom- Circuit Judges, and PETTINE,' Senior his failure to articulate a legal standard was related in its effect to Schedule I and mended that MDMA be placed into Sched- District Judge. and his reliance on insufficient record evi- ule I of the CSA. II substances. Comprehensive Drug dence; (b) the Administrator failed to give Abuse Prevention and Control Act of 1970, adequate weight to the evidence showing In March of 1984, pursuant to the proce- § 202(b)(1), as amended, 21 U.S.C.A. COFFIN, Circuit Judge. that placing MDMA into Schedule I would dures set out in the CSA, 28 U.S.C. 811(b),' § 812(b)(1). On November 13, 1986, the Administra- the Administrator submitted the DEA's create a barrier to medical research on the tor of the Drug Enforcement Administra- control recommendation to the Assistant 3. Drugs and Narcotics -46 drug; and (c) the rule is based upon incom- Alleged failure of administrator of tion ("DEA") issued a final rule placing the plete and arbitrary recommendations from Secretary for Health of the Department of Drug Enforcement Administration to con- substance 3,4-methylenedioxymethamphe the Secretary of Health and Human Servic- Health and Human Services ("HHS") for sider impact of determination to place sub- tamine ("MDMA") into Schedule I of the es. Petitioner urges this court to remand scientific and medical evaluation and for an stance on Schedule I upon legitimate scien- Controlled Substances Act ("CSA"), 21 the case to the DEA with instructions to HHS recommendation as to whether tific research was not improper. Compre- U.S.C. §§ 811, 812 (1987).¹ 51 Fed.Reg. place the substance MDMA into Schedule MDMA should be controlled. The HHS hensive Drug Abuse Prevention and Con- 36,552 (1986). In reaching this decision, III. evaluation was conducted by Dr. Charles the Administrator found that MDMA met Tocus, Chief of the Drug Abuse Staff of trol Act of 1970, § 202(b)(1), as amended, Although we are satisfied that these fi- all three of the statutory requirements for the Food and Drug Administration 21 U.S.C.A. § 812(b)(1). nal three claims do not require us to over- classification as a Schedule I substance, turn the rule, we believe that Dr. Grin- ("FDA"). Dr. Tocus stated in his affidavit 4. Administrative Law and Procedure namely, that he searched the FDA files and found spoon's first claim has considerable merit 364 (A) The drug or other substance has a no reference to MDMA. Based upon this and requires us to remand the scheduling Drugs and Narcotics -46 high potential for abuse. absence of information in the FDA files determination for reconsideration by the Department of Health and Human Ser- (B) The drug or other substance has no and a review of the information contained Administrator. After describing the ad- vices' adoption of analysis already per- currently accepted medical use in treat- in the DEA control recommendation carried ministrative history of the rule, we shall formed by Drug Enforcement Administra- ment in the United States. consider each of petitioner's claims in turn. out by Dr. Tocus, HHS responded by mak- tion that substance should have been classi- (C) There is a lack of accepted safety for ing minor (typographical) corrections in the fied in Schedule I without consulting any use of the drug or other substance under I. Administrative History. DEA's eight-factor analysis and concur- organization medical professionals or its medical supervision. ring in the recommendation that MDMA be In January of 1984, the DEA prepared a own panel of experts was harmless error, document entitled "Schedule I Control Rec- placed into Schedule I. and did not require rescheduling of sub- 21 U.S.C. § 812(b)(1). Dr. Lester Grinspoon, a psychiatrist and ommendation Under the CSA for 3,4-Me- Upon receiving the HHS evaluation and stance, where there was substantial evi- faculty member of the Harvard Medical thylenedioxymethamphetamine (MDMA)." recommendation, the Administrator issued dence to support classification. Compre- School, petitions this court to review the The control recommendation, which was a Notice of Proposed Rulemaking with re- hensive Drug Abuse Prevention and Con- final rule. Dr. Grinspoon seeks to conduct based upon information compiled from vari- gard to placing MDMA into Schedule I of trol Act of 1970, § 201(b, c), as amended, 21 U.S.C.A. § 811(b, c). research on the therapeutic use of MDMA ous DEA data sources and scientific and the CSA. 49 Fed.Reg. 30,210 (1984). La- and believes that the imposition of Sched- medical literature, considered all three ter, following the receipt of several com- ule I controls will effectively foreclose such 2. 21 U.S.C. § 811(b) provides that (2) Scientific evidence of its pharmacological Richard Cotton, Washington, D.C., for research. He cites four reasons for vacat- The Attorney General shall, before initiating effect, if known. petitioner. ing the Administrator's scheduling determi- proceedings under subsection (a) of this sec- (3) The state of current scientific knowledge Harry S. Harbin, Washington, D.C., with tion to control a drug or other substance regarding the drug or other substance. nation. The first reason advanced is that the Administrator applied the wrong legal and after gathering the necessary data, re- (4) Its history and current pattern of abuse. whom William F. Weld, Asst. Atty. Gen., quest from the Secretary a scientific and (5) The scope, duration, and significance of Criminal Div., Boston, Mass., Charles S. standards for "currently accepted medical medical evaluation, and his recommenda- abuse. Sapho, Chief, Narcotic and Dangerous use in treatment in the United States" and tions, as to whether such drug or other sub- (6) What, if any, risk there is to the public stance should be so controlled. health. Of the District of Rhode Island, sitting by desig. U.S.C. § 811. These listings are subject to (7) Its psychic or physiological dependence amendments and additions pursuant to 21 3. Section 811(c) requires the Administrator to liability. nation. U.S.C. § 811. Substances placed into Schedule I consider the following eight factors for each (8) Whether the substance is an immediate 1. The Act established five categories of sub- are subject to the most severe controls and drug proposed to be controlled under the CSA: precursor of a substance already controlled stances whose manufacture and distribution are penalties imposed by the Act. (1) [The drug's) actual or relative potential under this subchapter. subject to federal control. The Act's initial for abuse. 21 U.S.C. § 811(c). scheduling of substances can be found in 21 884 828 FEDERAL REPORTER, 2d SERIES GRINSPOON V. DRUG ENFORCEMENT ADMIN. 885 Cite as 828 F.2d 881 (lst Clr. 1987) ments and requests for a hearing, the Ad- medical supervision. Finally, the Adminis- If the court determines Congress has [1] The Administrator contends that ministrator referred the matter to an Ad- trator found that the DEA had sustained not directly addressed the precise ques- congressional intent favoring his interpre- ministrative Law Judge ("ALJ") with in- its burden of proving that MDMA has a tion at issue, the court does not simply tation of the CSA can be gleaned from the structions to "conduct a hearing for the high potential for abuse. The Administra- impose its own construction on the stat- language of the statute, its legislative his- purpose of receiving factual evidence and tor's final rule, effective November 13, ute, as would be necessary in the ab- tory, and the language and history of sub- expert opinion regarding the proposed 1986, placed MDMA into Schedule I. Dr. sence of an administrative interpretation. sequent legislative enactments designed to scheduling of MDMA." 51 Fed.Reg. 36,- Grinspoon appeals from this final rule un- Rather, if the statute is silent or ambigu- enhance the regulatory system established 552 (1986). During the course of the hear- der the CSA, 21 U.S.C. § 877. ous with respect to the specific issue, the by the CSA in 1970. In the alternative, he ing, the ALJ heard 33 witnesses and re- question for the court is whether the argues that if the intent of Congress is ceived 95 exhibits into evidence.⁴ On May II. Accepted Medical Use And Safety agency's answer is based on a permissi- ambiguous, then his construction of the 22, 1986, the ALJ issued a comprehensive Under The CSA. ble construction of the statute. statute is permissible in view of the statu- opinion finding that MDMA fit none of the Id. at 843, 104 S.Ct. at 2781-82 (footnote tory scheme.5 Our review of the sources three criteria prerequisite to placement in We turn first to petitioner's claim that omitted; emphasis supplied). identified by the litigants convinces us that Schedule I. Relying on the hearing testi- the Administrator erred in interpreting the phrases "accepted medical use in treatment It is undisputed that Congress has not Congress neither expressed nor implied an mony of experts in the health care commu- in the United States" and "accepted safety directly spoken to the question at issue affirmative intent regarding how the sec- nity, the ALJ concluded that MDMA had an for use here, namely, the proper means of inter- ond and third Schedule I criteria should be accepted medical use for treatment in the under medical supervision" in section 812(b)(1) to mean, in essence, "ap- preting the second and third criteria of interpreted. Nevertheless, these same United States, 21 U.S.C. § 812(b)(1)(B), and proved for interstate marketing by the section 812(b)(1). The absence of express sources-the language and structure of the an accepted safety for use under medical intent, however, does not compel us to pro- CSA and FDCA, the legislative history of supervision, 21 U.S.C. § 812(b)(1)(C). The FDA under the FDCA." Before embark- ceed to the deferential second step of the the CSA, and the subsequent handiwork of ALJ also found that the record did not ing on an analysis of that issue, however, Chevron scheme. As the Supreme Court Congress in the area of controlled sub- establish that MDMA had a "high" poten- we begin by explaining the appropriate indicated in a footnote to its Chevron opin- stance regulation-lead us to conclude that tial for abuse. 21 U.S.C. § 812(b)(1)(A). standard of review in a case, such as this, where a court must assess an agency's ion, "[i]f a court, employing traditional the Administrator's construction of subsec- The ALJ therefore recommended that tools of statutory construction, ascertains tions (B) and (C) of 21 U.S.C. § 812(b)(1) is MDMA be placed into Schedule III of the interpretation of a statute it administers. that Congress had an intention on the pre- contrary to congressional intent.6 CSA. cise question at issue, that intention is law The Administrator, however, declined to A. Standard of Review. and must be given effect." Id. at 843 n. 9, B. Statutory Language and Structure. accept the reasoning and scheduling recom- The Administrator argues correctly that 104 S.Ct. at 2781 n. 9. Recently the Su- The Administrator begins by arguing mendation of the ALJ. In his October 13, we must review his interpretation of the preme Court has reaffirmed this proposi- that the language of the CSA itself is evi- 1986, decision, the Administrator held that CSA in light of the guidelines set forth by tion, holding in INS v. Cardoza-Fonseca, dence of congressional intent favoring his the phrases "currently accepted medical the Supreme Court in Chevron U.S.A., Inc. U.S. 107 S.Ct. 1207, 94 L.Ed.2d construction of the statute. His argument use in treatment in the United States" and v. Natural Resources Defense Council, 434 (1987), that a court faced with a "pure is based on the definitions of terms chosen "accepted safety for use under medical Inc., 467 U.S. 837, 104 S.Ct. 2778, 81 question of statutory interpretation" by Congress in drafting the relevant provi- supervision" as used in the CSA, 21 U.S.C. L.Ed.2d 694 (1984). In Chevron the Court should rely upon traditional methods of sions of the CSA. He first cites the defini- § 812(b)(1), both mean that the FDA has explained that a reviewing court must em- statutory construction in an attempt to de- tion of the term "United States" as used in evaluated the substance for safety and ap- ploy a two-step analysis that focuses initial- termine the intent of Congress. Id. 107 "accepted medical use in treatment in the proved it for interstate marketing in the ly on the intentions of Congress: S.Ct. at 1221; International Union, UAW United States." 21 U.S.C. § 812(b)(1)(B). United States pursuant to the Federal v. Brook, 816 F.2d 761, 764-65 (D.C.Cir. This term is the only portion of the Sched- Food, Drug, and Cosmetic Act of 1938 First, always, is the question whether 1987) (applying "traditional tools" of statu- ule I criteria that Congress has expressly ("FDCA"), 21 U.S.C. § 355. From these Congress had directly spoken to the pre- tory construction to invalidate agency's in- defined in the CSA, providing that "[t]he premises, the Administrator reasoned that cise question at issue. If the intent of Congress is clear, that is the end of the terpretation of statutory language as con- term 'United States,' when used in a geo- because the FDA has not approved a new matter; for the court, as well as the flicting with intent of Congress). graphic sense, means all places subject drug application ("NDA") or investigation- al new drug application ("IND") authoriz- agency, must give effect to the unambig- 5. Contrary to the assertions of the Administra- § 811(a)(1)(B) (emphasis supplied). This ex- uously expressed intent of Congress. tor, this is not a situation in which Congress has plicit delegation of authority to apply prescribed ing interstate marketing of MDMA under expressly vested the Administrator with authori- statutory criteria is not equivalent to an explicit the FDCA, MDMA cannot be lawfully mar- Id. at 842-43, 104 S.Ct. at 2781 (emphasis ty to define general statutory criteria by issuing delegation of authority to define those criteria. keted and has neither a currently accepted supplied). In the absence of congressional regulations. Were this such a case, such regula- medical use in treatment in the United intent, however, the court must proceed to tions would be controlling unless they were 6. Our review of the legislative sources below "arbitrary, capricious, or manifestly contrary to also convinces us that the Administrator's inter- States nor an accepted safety for use under a second inquiry: the statute." Chevron, 467 U.S. at 843-44, 104 pretation is unreasonable and would be invalid S.Ct. at 2782. Here, the CSA expressly delegates 4. On July 1. 1985, while the hearing was pro- sions of the Act, 21 U.S.C. § 811(h)(1). 50 Fed. even under the second prong of the Chevron to the Attorney General only the authority to Reg. 23,118 (1985). The Administrator deter- test. See International Union, UAW v. Brock, ceeding, the Administrator placed MDMA into make "the findings prescribed by subsection (b) Schedule I of the Controlled Substances Act mined that this action was necessary to avoid an 816 F.2d at 765 n. 6. of section 812 of this title for the schedule in pursuant to the emergency scheduling provi- imminent hazard to the public safety. Id which (a) drug is to be placed." 21 U.S.C. GRINSPOON V. DRUG ENFORCEMENT ADMIN. 886 828 FEDERAL REPORTER, 2d SERIES 887 Cite as 828 F.2d 881 (1st Clr. 1987) to the jurisdiction of the United States." (emphasis supplied). We find this lan- this argument appears to have considerable marketing approval (or exemption) for any 21 U.S.C. § 802(28) (emphasis supplied). guage to be further evidence that the Con- merit. The Uniform CSA, like its federal of seven specific reasons. 21 U.S.C. Coupling this statutory definition of "Unit- gress did not intend "accepted medical use counterpart, creates five schedules of con- § 355(d)(1)-(7). Although approval may be in treatment in the United States" to re- trolled substances and, indeed, was mod- withheld because the substance lacks both ed States" with the dictionary definition of "accepted"-which means "generally ap- quire a finding of recognized medical use in eled on the federal CSA. 9 U.L.A. 187, 188 "safety", 21 U.S.C. § 355(d)(2), and "effica- proved" or "generally agreed upon"-the every state or, as the Administrator con- (1979).' But, while we agree that the Uni- cy" for a particular use, 21 U.S.C. tends, approval for interstate marketing of form CSA offers an interesting compari- Administrator argues that the phrase "ac- § 355(d)(5), it is equally possible for a sub- the substance. son, we fail to see how the interpretation of cepted medical use in treatment in the stance to be disapproved for interstate the Uniform CSA offered by the Commis- United States," 21 U.S.C. § 812(b)(1)(B), Nor does the dictionary definition of "ac- marketing because it lacks only one of sioners has any bearing at all on the intent must contemplate an administrative deter- cepted" offered by the Administrator con- these attributes, or because the application mination that the substance has been "gen- vince us that Congress intended FDA ap- of Congress, which enacted the federal fails to contain relevant patent information, erally approved" for use in treatment in proval to be the equivalent of the second CSA prior to the creation of the Uniform 21 U.S.C. § 355(d)(6), or even because the CSA. We can only conclude, therefore, "all places" subject to United States juris- and third Schedule I criteria. Use of the labeling proposed for the drug "is false or diction. In other words, FDA interstate term "accepted" in sections 812(b)(1)(B) and that this argument, despite its facial ap- misleading in any particular." 21 U.S.C. marketing approval is necessary to satisfy 812(b)(1)(C) may indicate that Congress in- peal, has no bearing on the claim that the § 355(d)(7). Thus, we find no necessary this criterion because, otherwise, the sub- tended the medical use or safety of the language of the federal CSA evidences con- linkage between failure to obtain FDA in- stance could not be deemed to be "general- substance to be "generally agreed upon," gressional intent to adopt the construction terstate marketing approval and a determi- but this alone does not inform us as to who of the statute favored by the Administra- ly approved". everywhere in the United nation that the substance in question is tor. States.¹ must generally be in agreement. The Ad- unsafe and has no medical use. Indeed, We find this argument to be strained and ministrator reads "accepted" to mean that While the Administrator's arguments fail the FDCA does not even mention the term the FDA must have approved the drug for to persuade us that Congress affirmatively unpersuasive. The CSA's definition of "medical use." In short, it is plainly possi- interstate marketing. Dr. Grinspoon, on intended his construction of the CSA, we "United States" plainly does not require ble that a substance may fail to obtain the other hand, prefers to interpret "ac- believe nevertheless that the language and the conclusion asserted by the Administra- interstate marketing approval even if it has cepted" as meaning that the medical com- structure of the two relevant statutes, the tor simply because section 802(28) defines an accepted medical use. munity generally agrees that the drug in CSA and the FDCA, are helpful in deter- "United States" as "all places subject to mining whether the Administrator's inter- Another possible reason for failure to the jurisdiction of the United States." 21 question has a medical use and can be used U.S.C. § 802(28) (emphasis supplied). Con- safely under medical supervision. Our con- pretation squares with congressional in- obtain FDA new drug approval is that the tent. Although, as the District of Colum- manufacture, distribution, and use of a gress surely intended the reference to "all clusion is that the term "accepted" does places" in section 802(28) to delineate the not cure the statute's ambiguity. We are bia Circuit has stated, "[t]he interrelation- substance might not involve interstate mar- simply unable to extrapolate from the ship between the two Acts [CSA and keting.¹⁰ Unlike the CSA scheduling re- broad jurisdictional scope of the CSA and drafters' choice of the word "accepted" and FDCA] is far from clear," National Orga- strictions, the FDCA interstate marketing to clarify that the CSA regulates conduct occurring any place, as opposed to every thereby ascertain a general congressional nization for Reform of Marijuana Laws provisions do not apply to drugs manufac- place, within the United States. As peti- intention favoring the interpretation ad- (NORML) v. DEA, 559 F.2d 735, 750 (D.C. tured and marketed wholly intrastate. vanced by the Administrator. Cir.1977), we are persuaded that this in- Compare 21 U.S.C. § 801(5) with 21 U.S.C. tioner aptly notes, a defendant charged In another argument focusing upon the terrelationship precludes the Administra- $ 321(b), 331, 355(a). Thus, it is possible with violating the CSA by selling controlled tor's reliance on the absence of FDA ap- that a substance may have both an accept- substances in only two states would not language of the statute, the Administrator urges us to adopt his interpretation of the proval as a substitute for the second and ed medical use and safety for use under have a defense based on section 802(28) if third Schedule I criteria under the CSA. CSA because it is entirely consistent with medical supervision, even though no one he contended that his activity had not OC- curred in "all places" subject to United The CSA clearly provides that a sub- has deemed it necessary to seek approval the interpretation of the phrase "accepted States jurisdiction. We add, moreover, medical use in treatment in the United stance may not be placed in Schedule I for interstate marketing. Indeed, as Dr. that the Administrator's clever argument States" employed in the Commissioners' unless it lacks both a "currently accepted Grinspoon argues, there is no economic or Notes to the Uniform Controlled Sub- medical use in treatment in the United other incentive to seek interstate market- conveniently omits any reference to the fact that the pertinent phrase in section stances Act, §§ 203-12, 9 U.L.A. 221-35 States" and "accepted safety for use ing approval for a drug like MDMA be- 812(b)(1)(B) reads "in the United States," (1979) ("Uniform CSA").8 At first glance, under medical supervision." The FDCA, cause it cannot be patented and exploited on the other hand, provides that a sub- commercially. The prospect of commercial 7. The Administrator does not confine this argu- Experimental substances found to have a po. stance may fail to obtain FDA interstate development, of course, is irrelevant to one ment to section 812(b)(1)(B), but also states that tential for abuse in early testing will also be "accepted safety for use under medical su- included in Schedule 1. When those sub- the criteria set out in Sections 205, 207, 209, lands have adopted the Uniform CSA. 9 U.L.A. pervision, 21 U.S.C. § 812(b)(1)(C), is equivalent stances are accepted by the Federal Food and and 211. Supp. 123-24 (1986). to FDA approval because. otherwise, the safety Drug Administration as being safe and effec- 9 U.L.A. at 221. of the substance could never be "generally tive, they will then be considered to have an 10. Indeed, Dr. Grinspoon argues that MDMA is agreed upon." accepted medical use for treatment in the 9. The Uniform CSA was approved for adoption a drug that has been legally manufactured and United States, and thus, will be eligible to be by the states in 1970. To date, 48 states, the used only within a particular state. Petitioner's 8. The Commissioners' Notes provide: shifted to an appropriate schedule based upon District of Columbia, Guam, and the Virgin Is- brief at 20. 828 FEDERAL REPORTER, 2d SERIES GRINSPOON V. DRUG ENFORCEMENT ADMIN. 889 888 Cite as 828 F.2d 881 (1st Clr. 1987) who, like Grinspoon, seeks only to do re- 'safety and efficacy' of narcotic and dan- D. Subsequent Legislation. use expedited procedures and rely upon the search. gerous drugs (e.g., whether such drugs are The Administrator has cited three subse- absence of FDA interstate marketing ap- These considerations tend to indicate that acceptable for medical use and safe for quent legislative enactments as support for proval, rather than the usual Schedule I the absence of FDA approval for interstate such use) be determined by [HHS] under his position that Congress has approved his criteria, only in temporary emergency situ- commerce does not foreclose the possibility the [FDCA]." Respondent's Brief at 17-18 construction of the second and third crite- ations suggests to us that these shorthand that a substance might still possess an (emphasis deleted). The Administrator's ria for Schedule I substances. Our review methods are not appropriate in routine (i.e., accepted medical use or even be considered conclusion is objectionable, however, be- of these legislative enactments, however, nonemergency) situations such as the one safe for use under medical supervision. It cause his parenthetical comment-equating leads us to find that the subsequent legisla- before us in the instant case. We do not appears, instead, that blind reliance on the a finding of "safety and efficacy" by the tion tends to weaken, not strengthen, the interpret the explicit reference to FDA ap- lack of FDA interstate marketing approval FDA with a finding of "accepted medical position espoused by the Administrator in proval in the "emergency scheduling" pro- could cause a substance to be placed in un- this litigation. We can only conclude, de- vision to mean, as the Administrator would use" and "accepted safety for use Schedule I, even though one or two of the spite the Administrator's claim that Con- have us believe, that Congress sought to der medical supervision"-is totally unsup- three requirements prescribed by Congress ported by the quoted passage from the gress has repeatedly approved his con- permit blind reliance on FDA standards as struction of the CSA, that Congress has a legitimate shortcut in the general run of for placement of a drug in Schedule I have House Committee Report. Nowhere does cases. not been proven. Based solely on the lan- Congress equate "safety and efficacy" un- never expressly or implicitly approved an der the FDCA with the second and third interpretation of section 812(b)(1) that Second, Congress amended the CSA guage of the CSA and the FDCA, there- Schedule I criteria contained in section would direct findings of "no currently ac- again in 1986 when it enacted the Con- fore, we find it unlikely that substituting the lack of FDA interstate marketing ap- 812(b)(1). This, indeed, is the point at issue cepted medical use" and "lack of accepted trolled Substance Analogue Enforcement proval for the statutory requirements that in this litigation, and we are loath to accept safety for use under medical supervi- Act, Pub.L. No. 99-570, §§ 1201-04, 100 sion" whenever a substance lacked FDA Stat. 3207 (codified at 21 U.S.C. a substance lack both an "accepted medical such a disingenuous argument. un- Second, the Administrator looks to the interstate marketing approval. Rather, we §§ 802(32)(A), 813). This amendment de- use" and "accepted safety for use history underlying the legislative schedul- are persuaded to the contrary that the sub- fines a "controlled substance analogue" as der medical supervision" is consistent with sequent enactments by Congress buttress a substance having a chemical structure the intent of Congress in enacting the CSA. ing of the drug alphacetylmethadol in our conclusion that the Administrator's and effect on the central nervous system We turn now to consider whether the legis- Schedule I for support. With regard to the construction of the CSA conflicts with con- substantially similar to that of a Schedule I lative history of the CSA confirms or re- scheduling of this substance, there is evi- or II controlled drug. 21 U.S.C. buts this tentative conclusion. dence that the Director of the Bureau of gressional intent. To demonstrate why this is so, we shall review each of the three § 802(32)(A). It provides that analogues of Narcotics and Dangerous Drugs represent- Schedule I and II controlled substances pieces of subsequently enacted legislation C. Legislative History. ed to Congress that the FDA had not is- relevant to the current dispute in the para- shall, to the extent intended for human The Administrator purports to have iden- sued an NDA or an IND for alphacetylme- graphs that follow. consumption, be subject to the same con- tified portions of the CSA's legislative his- thadol, and claimed that this lack of FDA trols and penalties as the controlled sub- tory that support his construction of the approval settled the issue whether alphace- First, in 1984, Congress amended the stances themselves. 21 U.S.C. § 813. As statutory language. First, he cites a pas- tylmethadol had a "currently accepted CSA to include an "emergency scheduling" the Administrator points out, the provision sage from the House Committee Report medical use." Because Congress eventual- provision. See 21 U.S.C. § 811(h). This expressly excludes from its definition of ly did schedule alphacetylmethadol in provision allows the Attorney General to that states: "controlled substance analogue," and hence Schedule I of the CSA, see 21 U.S.C. § 812, place certain substances into Schedule I on Under Reorganization Plan No. 1 of 1968 from the scope of the amendment's sub- Schedule I(a)(3), the Administrator con- a temporary basis without regard to the [reprinted in 1968 U.S.Code Cong. & stantive controls pending final scheduling, tends that it directly approved the statu- regular scheduling criteria and procedures Ad.News 4734] a Bureau of Narcotics any substance for which there is an ap- and Dangerous Drugs has been estab- tory interpretation he advances today. We if such emergency scheduling is "necessary proved new drug application or an exemp- are unpersuaded, however, that this isolat- to avoid an imminent hazard to the public lished in the Department of Justice to tion for investigational use under section ed instance-with no indication of express safety." 21 U.S.C. § 811(h)(1). This 355 of the FDCA. 21 U.S.C. regulate all these drugs (including legit- congressional approval or even tacit re- amendment to the CSA, however, expressly imate importation, exportation, manufac- § 802(32)(B)(ii), (iii). Again, however, we ture, and distribution) to prevent diver- liance on the-Director's statement-is rea- states that the Attorney General's authori- are unpersuaded by the Administrator's ar- son enough to defer to the Administrator's ty to schedule substances in this expedited sion from legitimate channels. Safety gument that explicit permission to rely on construction of the statute. Indeed, the manner does not apply where an "exemp- FDA standards in the case of analogues and efficacy will continue to be regulated under the Federal Food, Drug, and Cos- impermissibility of substituting FDCA tion or approval is in effect for the sub- evidences congressional approval of his use metic Act by [HHS]. standards for CSA scheduling criteria be- stance under section 355 of this title," 11 of this shorthand method in all scheduling comes even more apparent when we com- i.e., where the FDA has permitted the sub- determinations. We believe instead that H.R.Rep. No. 1444, 91st Cong., 2d Sess. stance to be marketed in interstate com- the authorization to impose Schedule I con- (1970), reprinted in 1970 U.S.Code Cong. pare the dearth of support in the legislative history for such an interpretation with the merce. Id. The fact that Congress ex- trols based on the lack of FDA approval, & Ad.News 4566, 4584 (hereinafter cited as language and history of several subsequent pressly authorized the Attorney General to rather than satisfaction of the scheduling "House Committee Report"). From this, the Administrator draws the proposition legislative enactments in the controlled 11. 21 U.S.C. § 355 is the section of the FDCA FDA interstate marketing approvals and exemp- that "Congress clearly intended that the substance field. describing the standards and procedures for tions. 828 2d-21 828 FEDERAL REPORTER, 2d SERIES GRINSPOON V. DRUG ENFORCEMENT ADMIN. 891 890 Cite as 828 F.2d 881 (1st Clr. 1987) criteria set out in section 812(b)(1), in the do not find the methaqualone legislation to three requirements for scheduling a sub- weight on the absence of FDA interstate unique situation of analogues intended for be persuasive authority for the proposition stance in Schedule I. We believe instead marketing approval, it has also determined human consumption constitutes a special, that the Administrator's interpretation of that, for the hearing opportunity to be a that a hearing procedure is unwarranted. and justifiable, exception to the general section 812(b)(1) is consistent with congres- significant one on these issues, the agency Clearly, this is not the case in the general procedure mandated by section 812(b)(1). sional intent. must remain flexible enough to weigh and administrative scheduling proceedings and consider claims raised at the administrative We believe, however, that in other cases the hearing requirement should be given involving nonanalogues, or analogues in- E. Need For A Meaningful Hearing. hearing to the effect that a substance has full effect rather than being shortcircuited tended for uses other than human con- an accepted use and is accepted as safe by blind reliance on the absence of FDA We believe there is yet one additional sumption, absolute reliance on the absence even though it is not approved for distribu- approval. policy reason, no doubt related to some of tion in interstate commerce. of FDA approval would be inappropriate the other factors already discussed, for re- and, indeed, contrary to the intent of Con- jecting the construction of the CSA ad- The importance of a meaningful hearing F. Conclusion. gress in enacting the CSA. vanced by the Administrator as contrary to prior to scheduling can best be appreciated For the reasons listed above, we conclude when one considers those situations for Third, in 1984, Congress legislatively congressional intent. Under the statutory that the Administrator erroneously applied placed the drug methaqualone in Schedule which Congress has permitted the Adminis- scheme set up by Congress, the Attorney an interpretation of the "accepted medical I. Despite its reputation as a widely trator to regulate substances in the ab- General may not schedule a substance un- use in treatment in the United States" and abused substance, methaqualone was uni- sence of a hearing. Neither the emergency der the CSA without first obtaining the "accepted safety for use under medical versally acknowledged to have an accepted scheduling provision, 21 U.S.C. § 811(h), recommendation of the FDA, through its supervision" criteria of section 812(b)(1) medical use and had been approved for nor the provision for treatment of con- parent agency, HHS, 21 U.S.C. § 811(b), that directly conflicts with congressional interstate marketing by the FDA. The trolled substance analogues, 21 U.S.C. and providing an "opportunity for a hear- intent. We therefore vacate the Adminis- House Committee Report concerning the § 813, requires the Administrator to hold a ing pursuant to the rulemaking procedures trator's determination that MDMA should scheduling of methaqualone stated: hearing prior to taking regulatory action. prescribed by [the Administrative Proce- be placed in Schedule I of the CSA and the [DEA] does not have authority to Congress crafted both of these sections to dure Act]." 21 U.S.C. § 811(a). It is plain, remand the rule for further consideration impose Schedule I controls on a drug serve as stop-gap measures to be employed therefore, that while Congress intended the by the DEA. On remand, the Administra- which has been approved by the [FDA] pending a final scheduling determination recommendation of HHS to have signifi- tor will not be permitted to treat the ab- for medical use. The statutory findings by the DEA, following a full evidentiary cant weight in the decisionmaking process, sence of FDA interstate marketing approv- required for agency scheduling decisions hearing, for the substance in question. it also intended that there be an opportuni- al as conclusive evidence that MDMA has clearly state that the agency may not, in Significantly, it is only in these provisions ty for a meaningful hearing after receipt of no currently accepted medical use and the absence of Congressional action, sub- for temporary controls pending final the HHS report. It would surely be ano- lacks accepted safety for use under medical ject drugs with a currently accepted scheduling that Congress has emphasized malous if the FDA's recommendation, supervision. medical use in the United States to the absence of FDA interstate marketing based solely on the absence of approval for Schedule I controls. approval, 21 U.S.C. § 811(h)(1) (emergency Petitioner Grinspoon has offered his own interstate marketing, sufficed to determine scheduling provision); 21 U.S.C. theory concerning the type of inquiry the H.R.Rep. No. 534, 98th Cong., 2d Sess. 4 the ultimate conclusion prior to the hear- § 802(32)(B)(ii), (iii) (controlled substance Administrator must make under the stat- (1984), reprinted in 1984 U.S.Code Cong. ing. analogue act). In the case of emergency ute. He urges us to adopt a standard for & Ad.News 540, 543. The Administrator If we were to accept the Administrator's scheduling, it appears that Congress has the second and third criteria that is based cites this passage in yet another attempt to construction of section 812(b)(1) in this already done the balancing and determined upon the opinion of members of the medical demonstrate congressional approval of his case, the opportunity for a meaningful that the risk of ongoing abuse amounting community. He contends that Congress position that a substance cannot have an hearing would be lost, and satisfaction of to an "imminent hazard to the public safe- drafted the CSA with this type of standard accepted medical use unless the FDA has already approved it for interstate market- the "accepted medical use" and "accepted ty" justifies temporary scheduling without in mind. To support this contention, Grin- ing. In fact, however, the actions of Con- safety" criteria would turn solely on the a hearing in the absence of FDA approval. spoon cites the testimony of two represent- gress with respect to methaqualone demon- existence of FDA approval for interstate Likewise in the latter case, Congress has atives of the Bureau of Narcotics and Dan- strate at most the converse of this proposi- marketing. A hearing on issues of the sort responded to the need for expedited investi- gerous Drugs ("BNDD"), DEA's predeces- tion: that FDA approval precludes schedul- required by the statute-Does the sub- gation and prosecution of "clandestine sor agency, during legislative consideration stance have an accepted medical use in chemists who develop subtle chemical vari- of Pub.L. No. 91-513, the Comprehensive ing of a substance in Schedule I., In other treatment in the United States? Is the ations of controlled substances (called ana- Drug Abuse Prevention and Control Act of words, the methaqualone legislation dem- onstrates Congress' belief that FDA ap- substance safe for use under medical su- logues or "designer drugs') for illicit distri- 1970. Michael R. Sonnenreich, Deputy bution and use," H.R.Rep. No. 848, 99th Chief Counsel of the BNDD, testified that proval is sufficient to establish the exist- pervision?-would be reduced to an empty ence of an accepted medical use, but not formality and, for participants like Dr. Cong., 2d Sess., pt. 1, 2 (1986), and permit- drugs in Schedule I would "have no medi- Grinspoon, would amount to an exercise in ted Schedule I controls to take effect with- cal use as determined by the medical com- that the lack of FDA approval-the issue in this case-necessarily negates the possibili- futility. We hesitate to interpret the CSA out first requiring a hearing so long as munity," and that "the medical communi- in a manner that would cause its important FDA approval is lacking. Thus, in both ty" would decide "whether or not the drug ty that the substance in question has an provision requiring a administrative hear- "emergency" situations for which Con- has [a] medical use Hearings on accepted medical use and is safe for use under medical supervision. We therefore ing to be meaningless as to two of the gress has seen fit to place particular Drug Abuse Control Amendments Before 892 828 FEDERAL REPORTER, 2d SERIES GRINSPOON V. DRUG ENFORCEMENT ADMIN. 893 Cite as 828 F.2d 881 (1st Clr. 1987) the Subcomm. on Public Health and Wel- found nothing to indicate how Congress 1. Legal Standard. there is "a substantial potential for the fare of the House Comm. on Interstate and affirmatively intended these two ambigu- The CSA provides no definition of the occurrence of significant diversions from Foreign Commerce, 91st Cong., 2d Sess. ous statutory phrases to be construed and phrase "high potential for abuse," but both legitimate channels, significant use by indi- 696, 718 (1970) ("House Hearings"). Like- applied. It appears to us that Congress parties agree that the legislative history of viduals contrary to professional advice, or wise, John Ingersoll, Director of the has implicitly delegated to the Administra- the statute provides guidance in this re- substantial capability of creating hazards BNDD, testified that substances placed in tor the authority to interpret these portions gard. Specifically, the report of the House to the health of the user or the safety of Schedule I would be those drugs that "the of the CSA, and we must therefore refrain Committee on Interstate and Foreign Com- the community." House Committee Re- medical profession has already determined from imposing our own statutory interpre- merce accompanying the bill that eventual- port, supra, at 4602. to have no legitimate medical use in the tation upon the agency. Chevron, 467 U.S. ly became the CSA sets forth four alterna- The Administrator argues that he applied United States." House Hearings at 678. at 843, 104 S.Ct. at 2781. Hence, to avoid tive legal standards for determining when the standards expressly approved by Con- While we acknowledge that the state- unduly infringing upon the Administrator's a substance possesses a "potential for gress, but Dr. Grinspoon complains that ments by the BNDD witnesses before the legitimate discretion to develop a legally abuse." Borrowing from regulations the Administrator articulated no standard House Subcommittee tend to support Dr. acceptable standard-i.e., one that does not promulgated under the FDCA, the House for showing that MDMA had a relative Grinspoon's position, we do not believe conflict with the intentions of Congress, Committee Report provides that the Admin- potential for abuse sufficient to warrant they are entitled to much weight as indicia and makes sense in light of the statutory istrator may determine a substance has placement in Schedule I. As Grinspoon of congressional intent in fashioning the language, the legislative history, and the potential for abuse if: notes, the passage from the legislative his- "accepted medical use" and "accepted safe- purposes of the entire legislative scheme- (1) There is evidence that individuals are tory quoted above provides guidance only ty for use under medical supervision" we remand the rule to the Administrator taking the drug or drugs containing such as to the minimum needed to show any criteria. See McCaughn v. Hershey Choc- for reconsideration and for further pro- a substance in amounts sufficient to cre- potential for abuse, in other words, enough olate Co., 283 U.S. 488, 493-94, 51 S.Ct. ceedings not inconsistent with this opinion. ate a hazard to their health or to the to justify a level of CSA control as low as 510, 512, 75 L.Ed. 1183 (1931) ("statements safety of other individuals or of the com- placement in Schedule V. It offers no made to committees of Congress munity; or guidance for assessing whether a sub- are without weight in the interpretation of III. Challenges Based on "Arbitrary (2) There is significant diversion of the stance should be subject to Schedule I con- a statute"). This is especially true where, and Capricious" Standard. drug or drugs containing such a sub- trols, the strictest imposed under the CSA, as here, there is no indication whatsoever Although a remand is necessary due to stance from legitimate drug channels; or which require a "high" potential for abuse. in either the legislative history or the histo- our above holding, we nonetheless feel (3) Individuals are taking the drug or For this, argues Grinspoon, the Administra- ry of any subsequent amendments that compelled to address the other issues drugs containing such a substance on tor must prove that MDMA has a high Congress concurred with the views ex- raised in Dr. Grinspoon's petition because their own initiative rather than on the potential for abuse relative to other sched- pressed by the witnesses. In short, we do they are likely to arise again when the basis of medical advice from a practition- uled substances and must base its proof on not find Grinspoon's evidence to be per- Administrator reconsiders the rule. er licensed by law to administer such existing levels of actual abuse "on the suasive on the issue of affirmative congres- drugs in the course of his professional streets." sional intent to have certain members of the medical community determine whether A. "High" Potential For Abuse. practice; or [2] While we acknowledge that the Ad- (4) The drug or drugs containing such a ministrator's final rule is silent with re- a substance has an "accepted medical use In addition to the "accepted medical use" substance are new drugs so related in spect to the legal standard required for a in treatment in the United States" or "ac- and "accepted safety" criteria discussed their action to a drug or drugs already finding of "high" potential for abuse, we cepted safety for use under medical above, the CSA also requires substances listed as having a potential for abuse to do not find the Administrator's action to be supervision.". identified for placement in Schedule I to make it likely that the drug will have the arbitrary and capricious. The fourth stan- The nature of our review further con- have a "high potential for abuse." 21 same potentiality for abuse as such dard contained in the segment of the Com- strains us from requiring the Administra- U.S.C. § 812(b)(1)(A). Dr. Grinspoon con- drugs, thus making it reasonable to as- mittee Report quoted above makes it quite tor to adopt Dr. Grinspoon's proposed con- tends that the Administrator's placement sume that there may be significant diver- clear that the Administrator can permissi- struction of section 812(b)(1). Although we of MDMA in Schedule I is arbitrary and sions from legitimate channels, signifi- bly reach a conclusion regarding a sub- find that the Administrator's present inter- capricious because the Administrator failed cant use contrary to or without medical stance's level of potential for abuse by pretation of the second and third Schedule to articulate a legal standard for assessing advice, or that it has a substantial capa- comparing the substance to drugs already I criteria contravenes congressional intent, MDMA's potential for abuse and because bility of creating hazards to the health of scheduled under the CSA. Here the Ad- we are unable to ascertain with any cer- the evidence in the record is insufficient to the user or to the safety of the communi- ministrator has done just that, offering tainty what Congress intended to be the support a finding that MDMA has a "high" ty. several findings concerning the evidence of proper interpretation of subsections (B) and potential for abuse. While conceding that MDMA has some potential for abuse, and House Committee Report, supra, at 4601. close structural and pharmacological sim- (C). In other words, while we are satisfied therefore should be scheduled under the The Committee Report goes on to state ilarity between MDMA and other sub- that Congress intended to preclude reliance CSA, Dr. Grinspoon insists that the Admin- that "potential for abuse" exists only when stances, such as MDA." which already on the absence of FDA approval in assess- ing whether a substance has an "accepted istrator has not proved, as he must for a 12. "MDA" is 3,4-methylenedioxyamphetamine narrowly defined, phenylisopropylamines or medical use" and "accepted safety for use Schedule I substance, that MDMA's poten- and, like MDMA, belongs to a class of com- amphetamines. under medical supervision," we have tial for abuse is high. pounds known as phenethylamines or, more GRINSPOON V. DRUG ENFORCEMENT ADMIN. 895 894 828 FEDERAL REPORTER, 2d SERIES Cite as 828 F.2d 881 (1st Clr. 1987) er words, "[e]ven if reasonable minds could and rats trained to recognize MDA also have been found to have a high potential 2. Substantial Evidence. also go the other way, we must uphold the recognized MDMA; (7) based on recent for abuse and have been placed in Schedule In reviewing the Administrator's conclu- [agency] if its ultimate finding is supported tests involving human subjects, MDMA can I or II. 51 Fed.Reg. 36,555-57 (1986). The sion regarding MDMA's potential for by substantial evidence in the record as a be described as maintaining the same po- Administrator also cited animal studies, hu- abuse, we must determine whether it is whole." NLRB v. J.K. Electronics, Inc., tency as MDA, but exhibiting subtle differ- man behavioral studies, and a survey of based on "substantial evidence," a term the 592 F.2d 5, 7 (1st Cir.1979). ences in the qualitative nature of the intoxi- MDMA users which suggest that MDMA is Supreme Court has defined as 'such rele- The question before us, therefore, is cation. related in its effects to Schedule I and II vant evidence as a reasonable mind might whether there is substantial evidence in the Dr. Grinspoon, in an item-by-item analy- substances such as LSD, cocaine, mesca- accept as adequate to support a conclu- administrative record to support the Ad- sis contained in the proposed findings of line, and MDA." We believe this approach sion.'' American Textile Manufacturers ministrator's determination that MDMA is fact and conclusions of law he submitted to to ascertaining MDMA's potential for Institute, Inc. v. Donovan, 452 U.S. 490, "so related in [its] action to a drug or the DEA, calls into question many of the abuse is entirely consistent with the statu- 522-23, 101 S.Ct. 2478, 2497, 69 L.Ed.2d drugs already listed as having a [high] Administrator's findings concerning tory scheme developed by Congress and 185 (1981) (quoting Universal Camera potential for abuse" that it is likely MDMA MDMA's similarity to other drugs with a therefore hold that the Administrator's Corp. v. NLRB, 340 U.S. 474, 477, 71 S.Ct. high potential for abuse. For instance, 456, 459, 95 L.Ed. 456 (1951)). The Court "will have the same potentiality for abuse method is not arbitrary and capricious.¹⁴ as such drugs." House Committee Report, Grinspoon agrees that MDMA is a member has further explained this lenient standard The question remains, of course, whether of review, stating that 'the possibility of supra, at 4601. In support of his conclu- of a family of psychoactive drugs, but dis- the evidence collected by the Administrator sion, the Administrator made 46 numbered putes the validity of the inference drawn drawing two inconsistent conclusions from is sufficient to justify his conclusion that the evidence does not prevent an adminis- findings related to MDMA's similarity to from the similarity by the Administrator. MDMA has a high potential for abuse. trative agency's findings from being sup- other drugs with a high potential for According to Grinspoon, "chemical similari- ported by substantial evidence." Id. abuse. These findings were based on sci- ty is not necessarily a good guide to the Since Dr. Grinspoon has also challenged (quoting Consolo v. Federal Maritime entific evidence concerning the chemical actual effects of a compound in the human this aspect of the scheduling determination as arbitrary and capricious, we turn next to Commission, 383 U.S. 607, 620, 86 S.Ct. structural similarity between MDMA and body." Petitioner's Brief at 37. Grinspoon 1018, 1026, 16 L.Ed.2d 131 (1966)). In oth- other Schedule I and II drugs; the similar notes that of the 28 known phenethyla- a discussion of this issue. pharmacological effects of MDMA and mines, 17 were not scheduled under the 13. The Administrator also considered that the ceives as the current low level of MDMA abuse these other drugs; animal drug discrimina- CSA as late as December 1983. Even a United Nations Commission on Narcotic Drugs "on the streets." For example, Grinspoon notes tion studies; animal self-administration subsequent review of these 17 substances has placed MDMA in Schedule I of the Conven- in his brief that the statistics above concerning the 41 evidentiary exhibits identified as MDMA studies; and recent studies of the neuro- by the World Health Organization's Expert tion on Psychotropic Substances and that MDMA occupies the same schedule in the Cana- toxic effects of MDMA and related drugs Committee on Drug Dependence resulted in during the period 1972-1985 are insignificant dian Food and Drug Act as MDA and LSD. 51 when one considers that MDMA accounted for on rats. Based on this evidence, the Ad- a recommendation that only nine of the Fed.Reg. 36,559 (1986). only one ten-thousandth of all DEA exhibits ministrator found, among other things, substances be scheduled by member na- 14. In addition to the evidence comparing compiled during this period. Likewise, the five that (1) MDMA is the N-methyl analogue of tions. Eight were thought harmless MDMA to other substances with a high potential laboratories with the potential to manufacture for abuse, the Administrator also considered MDMA account for only a minute fraction of MDA and retains the psychomimetic prop- enough to remain unscheduled.¹⁵ Also, re- evidence related to the "actual" abuse of MDMA the 2400 laboratories seized by the DEA from erties of MDA; (2) MDMA produces phar- ferring to the Administrator's finding that and made several findings in this regard. See 1972-1983. Furthermore, Grinspoon challenges macological effects in common with both MDMA, like MDA and amphetamine, is a 51 Fed.Reg. 36,557-36,558 (1986). These find- the finding that MDMA has been associated with ings reveal, among other things, that: (1) be- overdose deaths as "seriously suspect." central nervous system ("CNS") stimulants central nervous system stimulant, Grin- tween 1972 and April 1985, DEA laboratories While we appreciate Dr. Grinspoon's point like amphetamine and hallucinogens like spoon asserts that this evidence of pharma- identified 41 exhibits of MDMA, consisting of that MDMA abuse is low relative to other drugs MDA in animals; (3) MDMA and MDA cological similarity proves nothing. Sever- 60,000 dosage units; (2) from July 1985, when that seem to be more popular "on the street," we MDMA was temporarily placed in Schedule I produce the same spectrum of pharmaco- al other substances also fit this description, do not believe that this fact precludes the Ad- ministrator from finding that MDMA has a high logical effects in mice, dogs, and monkeys including caffeine and six of the eight pursuant to the Administrator's emergency scheduling powers, up to the time that the final when observed during toxicity studies; (4) phenethylamines that are neither currently potential for abuse. Grinspoon's argument rule was promulgated, 14 MDMA exhibits, con- overlooks the importance of the term "poten- MDMA, like MDA, amphetamine, and controlled nor recommended for control by sisting of 35,000 dosage units, had been identi- tial" in section 812(b)(1)(A) and runs contrary fied by DEA laboratories; (3) DEA has encoun- methamphetamine, produces neurotoxic ef- WHO. Based on this, Grinspoon concludes tered five laboratories capable of clandestinely to the explicit intent of Congress that the Ad- fects when administered to animals; (5) that the mere fact that a substance is a producing kilogram quantities of MDMA; (4) ministrator "not be required to wait until a the estimate of one DEA witness Is that street number of lives have been destroyed or substan- MDMA and MDA may both produce the CNS stimulant does not necessarily imply distribution of MDMA has increased from 10,- tial problems have already arisen before desig- same neurotoxic effects to serotonergic that it has a high potential for abuse. 000 dosage units in 1978 to 30,000 dosage units nating a drug as subject to the controls of the nerves in humans; (6) in drug discrimina- In addition, Dr. Grinspoon (1) attacks the per month in 1985; (5) according to Dr. Grin- bill." House Committee Report, supra, at 4602. tion tests, rats trained to recognize amphet- Administrator's other findings concerning spoon himself, MDMA is being taken by a grow. So long as the Administrator can marshal sub- ing number of people, particularly students and stantial evidence to demonstrate that MDMA is amine also recognized MDA and MDMA, MDMA's LD-50 rating 16 as being irrele- young professionals, in a casual and recreation- sufficiently similar to scheduled drugs with a al manner; and (6) MDMA is reported to have "high potential for abuse," we will sustain his 15. These eight are clobenzorex, fenbutrazate, 16. "LD-50" signifies the dose of a given drug been associated with two overdose deaths. determination regardless of existing levels of furfenorex, morazone, para-oxyamphetamine, that will kill 50% of the animals treated with 4-bromo-2,5-dimethoxyphenethylamine. N.N- that dose. Dr. Grinspoon attacks these findings of actual actual abuse. dimethylamphetamine, and N-ethyl-3,4-methy- abuse, focusing on the need to assess the relative lenedioxyamphetamine. level of actual abuse and stressing what he per- 896 828 FEDERAL REPORTER, 2d SERIES GRINSPOON v. DRUG ENFORCEMENT ADMIN. 897 Cite as 828 F.2d 881 (1st Clr. 1987) vant to the "potential for abuse" inquiry; the impact of a scheduling decision on legit- MDMA have available avenues by which to section 811(b) request for a scientific and (2) discounts the importance of findings imate research amounts to arbitrary and pursue such research." Id. medical evaluation; neglected to consult that MDMA is neurotoxic when adminis- capricious action on the part of the Admin- Second, and more importantly, Dr. Grin- any organization of medical professionals tered to rats; (3) questions the relevancy of istrator because he did not weigh all rele- spoon has identified nothing in the CSA, its or even the FDA's own panel of experts, the findings related to animal drug discrim- vant factors in making his decision. Motor legislative history, or its implementing reg- the Drug Abuse Advisory Committee; and ination studies; and (4) asserts that the Vehicle Manufacturers Association v. ulations that can be read to require the simply rubber-stamped the Administrator's Administrator has incorrectly interpreted State Farm Mutual Insurance Co., 463 Administrator to consider the impact of a conclusion by adopting the section 811(c) the results of two animal self-administra- U.S. 29, 42-43, 103 S.Ct. 2856, 2866, 77 scheduling determination upon legitimate eight-factor analysis already performed by tion studies. We have reviewed Dr. Grin- L.Ed.2d 443 (1983). To buttress his conten- scientific research. From our review of the DEA. There is also evidence that FDA spoon's item-by-item analysis closely, but tion, Grinspoon recites a litany of legal, the CSA, we can only conclude that Con- analysts failed to forward a letter received administrative, and practical obstacles that gress has already weighed the costs and from the National Institute of Drug Abuse, find no basis sufficient to overturn the hinder researchers seeking to conduct ex- benefits of legitimate research on danger- which stated that the evidence cited by the Administrator's decision. Grinspoon's rein- DEA did not support the existence of abuse terpretation of the scientific evidence be- periments with Schedule I drugs. These ous drugs and has determined, in a cate- obstacles include mandatory FDA approval gorical manner, that if the three Schedule I potential in animals, to either the FDA fore the agency surely demonstrates that the available evidence does not inexorably of research involving Schedule I sub- criteria are satisfied, see 21 U.S.C. Commissioner or the Assistant Secretary of stances, 21 C.F.R. § 1301.42(a)-(c); manda- § 812(b)(1), then the substance should be HHS prior to the issuance of the HHS lead to a conclusion that MDMA is similar to drugs possessing a high potential for tory special registration with the DEA, 21 subject to Schedule I controls even if this recommendation to the Administrator." abuse. But, faced with such uncertainty, C.F.R. §§ 1301.33, 1301.42; mandatory re- action will create administrative and other [4] Despite these alleged procedural we must defer to the conclusion reached by porting and security procedures beyond burdens for researchers. Here there is no shortcomings, we fail to see how the proce- the Administrator, even if we may have those required for drugs placed in Sched- dispute that the Administrator considered dure followed by HHS tainted the Adminis- favored Dr. Grinspoon's approach had we ules II through V; unavoidable bureaucrat- all of the section 812(b)(1) criteria in arriv- trator's determination. The CSA does not studied the evidence in a de novo fashion. ic delays; and other adverse impacts due to ing at his final rule, so we are left with a specify the steps to be taken by HHS; it In reaching this conclusion, we follow the the grave concern caused by a substance's situation in which there can be no com- simply requires the Administrator to re- well-established maxim that "[w]here the placement in Schedule I, such as difficulty plaint that the Administrator failed to con- quest from the Secretary of HHS a scien- agency presents scientifically respectable sider any relevant factor. tific and medical evaluation. 21 U.S.C. in obtaining volunteers for clinical studies evidence which the petitioner can contin- and, for academic researchers, difficulty in § 811(b). Moreover, the HHS recommen- ually dispute with rival, and we will as- C. Reliance Upon HHS Evaluation And dation to schedule a substance is not bind- securing approval from institutional review sume, equally respectable evidence, the Recommendation. boards. ing 18 and, indeed, serves to trigger an ad- court must not second-guess the particular Dr. Grinspoon's final dissatisfaction with ministrative hearing at which interested way the agency chooses to weigh the con- [3] Again, we do not doubt that Dr. the final rule is the Administrator's alleged persons may introduce evidence to rebut flicting evidence or resolve the dispute." Grinspoon has correctly identified several reliance on the conclusions recommended the Secretary's scheduling recommenda- Asarco, Inc. v. OSHA, 746 F.2d 483, 490 ways in which the placement of MDMA in by HHS on the criteria enumerated in sec- tion. Ultimately, of course, responsibility (9th Cir.1984) (quoting United Steelwork- Schedule I will impede his research and the tion 812(b)(1). Grinspoon argues that the rests with the Administrator, not HHS, to ers of America v. Marshall, 647 F.2d 1189, efforts of other researchers interested in determination by the Secretary of HHS ensure that the final rule rests on permissi- 1263 (D.C.Cir.1980), cert. denied, 453 U.S. exploring the possibility of clinical uses for was arbitrary and capricious and not in ble legal standards and substantial evi- 913, 101 S.Ct. 3148, 69 L.Ed.2d 997 (1981)). MDMA. We must conclude, nevertheless, accordance with law, and that all relevant dence. It is true that the Administrator We find this maxim to have particular that the existence of such hurdles does not scientific and medical evidence was not be- twice mentioned the HHS recommendation force in a case such as this because, as one render the Administrator's scheduling deci- fore the Secretary at the time of the deter- in his final rule, once in relation to the court has explained, "[a]ppellate courts sion arbitrary and capricious. First, it is mination. The record, in fact, reveals that "accepted medical use" criterion and once have neither the expertise nor the re- simply untrue that the Administrator failed HHS performed in a less than admirable in relation to the "high potential for abuse" sources to evaluate complex scientific to consider the impact on medical research fashion in making its recommendation to criterion. With regard to the first mention, claims." Thompson Medical Co. v. FTC, that would be caused by a decision to place the Administrator. The record indicates however, we have already determined that 791 F.2d 189, 196 (D.C.Cir.1986), cert. de- MDMA in Schedule I. In the final rule, the that HHS failed to look beyond its own this aspect of the case must be remanded nied, - U.S. 107 S.Ct. 1289, 94 Administrator states explicitly that he files upon receiving the Administrator's and reconsidered because the Administra- L.Ed.2d 146 (1987). "read with interest the comments from var- 17. Dr. Grinspoon also complains that the Acting 18. According to section 811(b), the HHS recom- ious parties in the record concerning the Assistant Secretary of Health concluded errone- mendation is binding as to "scientific and medi- B. Impact Of Scheduling On Research. effect placement of MDMA into Schedule I ously that MDMA had a "high" potential for cal" matters, but not with respect to the appro- Dr. Grinspoon also takes issue with the would have on legitimate research into the abuse because the recommendation of FDA's priate schedule in which to place a particular Administrator's alleged failure to consider substance." 51 Fed.Reg. 36,559 (1986). Deputy Commissioner described MDMA's poten- substance. The exception to this rule is that, "if tial for abuse as "significant," rather than the Secretary recommends that a drug or other evidence tending to show that placement of After several paragraphs discussing the "high." In light of the fact that the FDA Deputy substance not be controlled. the Attorney Gener- MDMA in Schedule I would strongly dis- contours of the additional Schedule I con- Commissioner recommended placement of al shall not control the drug or other sub- courage medical research on the drug. trols, the Administrator concludes that MDMA in Schedule I, we attribute no signifi- stance." 21 U.S.C. § 812(b) (emphasis sup- cance to this semantic argument. plied). Grinspoon contends that failure to consider "those who wish to conduct research with 898 828 FEDERAL REPORTER, 2d SERIES FURMAN V. CIRRITO 899 Cite as 828 F.2d 898 (2nd Clr. 1987) tor interpreted the statutory language in a owners of partnership pursuant to RICO ate" purchase of partnership at higher Before VAN GRAAFEILAND, manner that is contrary to the intent of statute. The United States District Court price was inadequate to establish that oth- NEWMAN and PRATT, Circuit Judges. Congress. Because, on remand, the Ad- for the Southern District of New York, er firm made offer to purchase. 18 U.S. ministrator will not be able to rely on lack Irving Ben Cooper, J., 578 F.Supp. 1535, C.A. §§ 1961-1968. VAN GRAAFEILAND, Circuit Judge: of FDA approval to demonstrate the ab- dismissed action for failure to state claim, 3. Commerce =82.72 This is an appeal from an order of the sence of an accepted medical use, we need and appeal was taken. The Court of Ap- Allegations by minority partners that United States District Court for the South- not discuss any possible reliance on the peals, 741 F.2d 524, affirmed. On petition their signatures on written contract for ern District of New York (Cooper, J.) HHS recommendation regarding the ab- for writ of certiorari, the United States sale of partnership assets were coerced by granting appellees' motion under Fed.R. sence of an accepted medical use. With Supreme Court, 105 S.Ct. 3550, vacated. criminal conduct on part of majority part- Civ.P. 12(b)(1) and (6) to dismiss appellants' regard to the second mention, we believe that the Administrator's conclusion that Following vacation, 779 F.2d 36, and on ners and that minority partners were complaint, and from the judgment entered MDMA has a high potential for abuse is remand, the district court concluded that "forced to accept employment" on unfavor- pursuant thereto. For the reasons that amply supported by a substantial amount complaint failed to allege any continuity of able terms was too conclusory to support follow, we affirm. of independent evidence. Because we be- activity and dismissed RICO cause of ac- charge of criminal wrongdoing in order to lieve that the Administrator's finding with tion, and appeal was again taken. The maintain action under RICO statute; each Appellants' complaint states three causes of action, two that are state law claims of regard to MDMA's potential for abuse is Court of Appeals, Van Graafeiland, Circuit partner had right to negotiate on his or her justified even in the absence of the HHS Judge, held that: (1) sale of partnership behalf whether, and on what terms, he or partnership fraud and breach of fiduciary recommendation to place MDMA in Sched- assets did not constitute wrongdoing to she was willing to become associated with duty and a third grounded on the Racke- support RICO action; (2) majority partners purchasing partnership, and even if minori- teer Influenced and Corrupt Organizations ule I, we hold that any reliance on the HHS were not guilty of any criminal conduct ty partners lacked sufficient sophistication Act (RICO), 18 U.S.C. §§ 1961-68. It twice evaluation by the Administrator consti- tutes, at most, harmless error. based on alleged failure to promptly inform to know that they could not be bonded over has been dismissed by the district court. For the foregoing reasons, the rule is to purchasing partnership without their The first dismissal was based on appel- minority partners that they would be re- vacated and remanded to the Adminis- consent, they made no allegation of any- lants' failure to allege a separate, distinct quired to sign written contract with pur- trator for further proceedings consistent thing that prevented them from refusing to racketeering enterprise injury. 578 chasing partnership; and (3) even if minori- sign contract unless they received more F.Supp. 1535 (S.D.N.Y.1984). This Court's with this opinion. ty partners spelled out some form of crimi- favorable treatment. 18 U.S.C.A. §§ 1961- affirmance of that decision, 741 F.2d 524, nal fraud on part of majority partners, they was vacated by the Supreme Court, 473 1968. KEY NUMBER SYSTEM failed to allege pattern of racketeering ac- U.S. 922, 105 S.Ct. 3550, 87 L.Ed.2d 672 tivity conducted in affairs of "enterprise." 4. Commerce =82.72 (1985), on the basis of its holdings in Sedi- Assuming that minority general part- ma, S.P.R.L. v. Imrex Co., 473 U.S. 479, Affirmed. ners' complaint spelled out some form of 105 S.Ct. 3275, 87 L.Ed.2d 346 (1985), and George C. Pratt, Circuit Judge, filed criminal fraud on part of majority partners American Nat'l Bank & Trust Co. v. Har- Aaron J. FURMAN, Martin J. Joel, Jr., dissenting opinion. in selling partnership assets, complaint oco, Inc., 473 U.S. 606, 105 S.Ct. 3291, 87 Alvin Katz, Francis P. Maglio, Harvey failed to allege pattern of racketeering ac- L.Ed.2d 437 (1985) (per curiam). Following Sheid, Everard M.C. Stamm and Robert tivity conducted in affairs of "enterprise" remand to the district court, appellees C. Stamm, Plaintiffs, to enable minority partners to maintain 1. Partnership 70, 97 moved to dismiss for failure to allege a Martin J. Joel, Jr., Harvey Sheld, RICO action; at time allegedly wrongful Rights and obligations of partners, as "pattern of racketeering activity", 18 Everard M.C. Stamm and Robert acts occurred, majority partners were not between themselves, are fixed by terms of U.S.C. § 1962(c), or, in the alternative, to C. Stamm, Plaintiffs-Appellants, functioning as continuing unit in ongoing partnership agreement; even terms which compel arbitration pursuant to the Federal organization, as they were acting solely on V. permit self-dealing by partner will be en- Arbitration Act, 9 U.S.C. 1-14. Relying their own to prevent alleged enterprise John CIRRITO, Harold S. Coleman, John forced. on Sedima, supra, 473 U.S. at 496 n. 14, from being ongoing, continuing unit A. Miller, Francis G. Rea, Peter M. Toc- 105 S.Ct. at 3285 n. 14; id. at 527-28, 105 through sale of partnership. 18 U.S.C.A. zek and A.J. Yorke, Defendants-Appel- 2. Commerce -82.72 S.Ct. at 3289-90 (Powell, J., dissenting), §§ 1961-1968. lees. Allegations by minority shareholders and cases that followed, the district court No. 18, Docket 86-7283. of partnership to effect that majority mem- held that racketeering activity must be con- bers committed mail fraud in selling assets Seymour Shainswit, New York City (Coo- tinuous and related in order to constitute a United States Court of Appeals, Second Circuit. of partnership was frivolous, and thus per Cohen Singer Ecker & Shainswit and pattern and must be ongoing or occur in could not support action brought pursuant Steven E. Levitsky, New York City, of more than one criminal episode. Although Argued Oct. 20, 1986. to RICO statute; partnership agreement counsel), for plaintiffs-appellants. the district court felt that appellees' al- Decided Sept. 1, 1987. gave absolute and sole discretion to majori- Max Gitter, New York City (Paul, Weiss, leged acts were related, it concluded that ty members to sell partnership assets, and Rifkind, Wharton & Garrison and Dorothy the complaint failed to allege any continui- further, allegation that principal of another E. Roberts, New York City, of counsel), for ty of activity, and dismissed the RICO Minority general partners of partner- ship brought civil claim against majority brokerage firm was "prepared to negoti- defendants-appellees. cause of action. The district court held Federal Register / Vol. 57. No. 59 / Thursdav. March 26. 1992 / Notices 1049 Tanif Act of 1930. On February 4. 1992. FOR FURTHER INFORMATION CONTACT: DEA's interpretation of the term the Commission scheduled a public Joseph H. Detimar. (202) 927-5660. (TDD "currently accepted medical use in hearing in connection therewith for for hearing impaired: (202) 927-5712. treatment in the United States." March 26. 1992. On March 17. 1992. the SUPPLEMENTARY INFORMATION: Alliance for Cannabis Therapeutics V. Commission received notice of Additional information is contained in DEA. 930 F.2d 936. withdrawal from the only scheduled the Commission's decision. To purchase Following a review of the entire witness for the hearing scheduled for a copy of the fuil decision. write to. call. record in this matter. and a March 26. 1992. Therefore. the public or pick up in person from: Dynamic comprebensive re-examination of the hearing in connection with this Concepts. Inc.. room 2229. Interstate relevant statutory standard. I conclude investigation (scheduled to be held Commerce Commission Building. that marijuana has no currently beginning at 9:30 a.m. on March 26. 1992. Washington. DC 20423. Telephone: (202) accepted medical use and must remain at the U.S. International Trade 289-4357/4359. (Assistance for the in Schedule I. Further hearings are Commission Building. 500 E Street. SW.. hearing impaired is available through unnecessary since the record is Washington DC). is cancelled. TDD services (202) 927-5721.) extraordinarily complete. all parties h EFFECTIVE DATE: March 20. 1992. Decided March 11. 1992. ample opportunity and wide latitude 1 FOR FURTHER INFORMATION CONTACT: By the Commission. Chairman Philbin. Vice present evidence and to brief all Edward Carroll (202-205-1819). Office of Chairman McDonaid. Commissioners relevant issues. and the narrow questi Public Affairs. U.S. International Trade Simmons. Phillips. and Emmett. on remand centers exclusively on this Commission. Hearing impaired persons Sidney L Strickland. r., Agency's legal interpretation of a can obtain information on this study bv Secretary. statutorily-created standard. contacting the Commission's TDD !FR Doc. 92-7017 Filed 3-25-92: 045 ami Summary of the Decision terminal on (202-205-1810). BILLING CODE 7035-01- By order of the Commission Does the marijuana plant have any currently accepted medical use in Dated: March 24. 1992. treatment in the United States. within Kenneth R. Mason. DEPARTMENT OF JUSTICE the meaning of the Federal Controlle Secretary. Drug Enforcement Administration Substances Act. 21 U.S.C. 801. et seq. FR Duc 92-7160 Filed 3-25-92. 8.45 and Put simply. is marijuana good medici: BILLING CODE 7020-02-M [Docket No. 86-221 for illnesses we all fear. such as mult. sclerosis (MS). glaucoma and cancer? Marijuana Scheduling Petition: Denial The answer might seem obvious INTERSTATE COMMERCE of Petition; Remand based simply on common sense. COMMISSION AGENCY: Drug Enforcement Smoking causes lung cancer and othe (Finance Docket No. 32016| Administration. Justice. deadly diseases. Americans take the ACTION: Final order. medicines in pills. solutions. sprays. Sioux & Western Railroad Co.- shots. drops. creams and sometimes Construction Exemption-Charles SUMMARY: This is a final order of the suppositories. but never by smoking. County, Mo; Notice Administrator of the Drug Enforcement medicine prescribed for us today is Administration (DEA) concluding the smoked. AGENCY: Interstate Commerce plant material marijuana has no With a little homework. one can le Commission. currently accepted medical use and that marijuana has been rejected as ACTION: Notice of exemption. denying the petition of the National medicine by the American Medical SUMMARY: Pursuant to 49 U.S.C. 10505. Organization for Reform of Marijuana Association. the National Multiple the Interstate Commerce Commission Laws (NORML) to reschedule marijuana Sclerosis Society. the American conditionally exempts from the prior from Schedule I to Schedule il of the Claucoma Society. the American Controlled Substances Act. approval requirements of 49 U.S.C. 10901 Academy of Ophthalmology the the construction by the Sioux & Western EFFECTIVE DATE: March 26. 1992. American Cancer Society. Not one Railroad Company of approximately 2 FOR FURTHER INFORMATION CONTACT: American health association accepts miles of rail line between the Sioux Office of Congressional and Public marijuana as medicine. Plant and a Union Pacific Railroad Affairs. 202-307-7363. For the last half century. drug Company line in Charles County. MO. evaluation experts at the United Sta: SUPPLEMENTARY INFORMATION: DATES: The exemption will not become Food and Drug Administration (FDA Background have been responsible for protecting effective until the environmental process :s completed. At that time. the On December 21. 1989. the former Americans from unsafe and ineffect Commission will issue a further decision Administrator of DEA. following new medicines. Relying on the same addressing the environmental matters rulemaking on the record. which scientific standards used to judge al. and establishing an effective date for included a hearing before an other drugs. FDA experts repeatedly the exemption. if appropriate. Petitions administrative law judge. issued a final have rejected marijuana for-medical in reopen must be filed by April 15. 1992. order concluding the plant material Yet claims persist that marijuana ADDRESSES: Send pleadings referring to marijuana has no currently accepted medical value. Are these claims true medical use. and denying the petition of What are the facts? Finance Docket No. 32016 to: NORML to reschedule marijuana from Between 1987 and 1988. DEA and :1 Office of the Secretary. Case Control Schedule 1 to Schedule II of the NORML under the guidance of an Branch. Interstate Commerce Cummission. Controlled Substances Act. 54 FR 63767. administrative law judge. collected Washington. DC 20423. 'I Petitioner S representative: John R. Moim. On April 26. 1991. the United States relevant information on this subject Esquire. Troutman. Sanders. Lockerman Court of Appeals for the District of Stacked together it stands nearly fiv and Ashmore. 1400 Candler Building. 127 Columbia Circuit remanded the matter feet high. is there reliable scientific Peachtree Street. NE.. Atlanta. GA 30303. to the Administrator for clarification of evidence that marijuana is medicall 10500 Federal Register / Vol. 57. No. 59 / Thursday. March 26. 1992 / Notices effective. If it has medical value. do its blood pressure if they experiment with "Randamized Double Blind Comparis benefits outweight its risks? What do marijuana. For MS and glancoma of Delta-9-Tetrahydrocannabinol (TH) America's top medical and scientific patients who must take medications for and Marijuana As Chemotherapy experts say? Would they prescribe it for the rest of their lives, experimenting Antiemetics," (Meeting Abstract) 3 their patients. their families. their with marijuana poses the additional Proceedings of the Annual Meeting of friends? risks of lung cancer. emphysema. the American Society of Clinical As the current Administrator of Drug bladder cancer and leukemia. Oncology 91 (1984). Enforcement. and as a former United Many risks remain unknown. During the 1970's and 1980's. a num States District Judge. I have made a Marijuana contains over 400 separately of states set up research programs to detailed review of the evidence in this identified chemicals. No one knows all record to find the answers. give marijoana to cancer and glaucom the effects of burning these chemicals There are significant short-term side patients. on the chance it might help. together and inhaling the burnt mix. Are effects and long-term risks linked to Some people point to these programs these risks outweighed by medical proof of marijuana's usefulness. smoking marijuana. Marijuana is likely benefits? to be more cancer-causing than tobacco: Unfortunately. all research is not There are scientific studies showing damages brain cells: causes lung necessarily good scientific research. pure THIC (Delta-9- problems. such as bronchitis and These state programs failed to follow Tetrahydrocannabinol). one of the many responsible scientific methods. Patier emphysema: may weaken the body's chemicals found in marijuana. has some antibacterial defenses in the lungs: took marijuana together with their effect in controlling nausea and lowers overall blood pressure. which regular medicines. so it is impossible vomiting. Pure THC is pharmaceutically could adversely affect the supply of say whether marijuana helped them. made in a clean capsule form. called Observations or results were not blood to the head: causes sudden drops Marmol. and is evailable for use by the in blood pressure (orthostatic scientifically measured. Procedures medical community. More information hypotension). rapid heart beat were so poor that much critical resea on Marimol can be found in the data were lost or never recorded. (tachycardia). and heart palpitations: "Physicians" Desk Reference. available suppresses futeinizing bormone in most libraries. Although these programs were well- secretion in women. which affects the Since marijuana contains THC. you intentioned. they are not scientific pr production of progesterone. an might think marijuana also would be of anything. important female hormone: causes effective. However. the effect of taking a Some people refer to a study by anxiety and panic in some users drug in combination with other Doctor Thomas Ungerleider as proof because of its mind-altering effects: chemicals is seldom the same as taking marijuana reduced nausea in bone produces dizziness. trouble with just the pure drug. As already noted. marrow transplant patients. thinking. trougle with concentrating. marijuana contains over 400 other Unfortunately. Doctor Ungerleider fatigue. and sleepiness: and impairs chemicals. not just THC. There are no neglected to follow responsible motor skills. reliable scientific studies that show scientific methods in his study. Like As a plant. marijuana can contain marijuana to be significantly effective in state programs. it proves nothing. Dc bacteria capable of causing serious controlling nausea and vomiting. People Ungerleider chose not to publish his infections in humans. such as refer to the Sallan study as proving study evidently because of its seriou salmonella enteritidis. Klebsiella marijuana's effectiveness. They are weaknesses. He admitted as much " pneumoniae. group D Streptoccoccus mistaken. The study involved questioned under oath. and pathogenic aspergillus. pure THC not marijuana. People refer to Those who say there are reliable Several of these risk stand out. The the Chang study to support marijuana's scientific studies showing marijuana immune systems of cancer patients are effectiveness. They also are mistaken. an effective drug for teating nausea weakened by radiation and Doctor Chang tested the combination of vomiting are wrong. No such studies chemotherapy. leaving them susceptible pure THC and marijuana to treat nausea exist. in infection. If they experiment with and vomiting. The preliminary results he Our nation's top cancer experts re marijuana to control nausea. they risk got were probably due to the THC. not marijuana for medical use. Doctor D weakening their immune systems further the marijuana. Because he tested the S. Ertinger. a professor of oncology and exposing themselves to the combination. we cannot tell just what the Johns Hopkins University Schoo infection-causing bacteria in the plant. It effects can be attributed to marijuana Medicine. an author of over 100 IS estimated. for example. that at alone. People cite a third study. done by scholarly articles on cancer treatme: Memorial Sloan-Kettering Cancer Doctor Levitt. as proof marijuana is and a nationally respected cancer Center 60 patients die each year from effective. They are mistaken. Doctor expert. testified: pathogenic aspergilhus infections. Levitt compared marijuana to THC in Glaucoma patients face possible There is no indication that marijuana controlling nausea and vomiting. and he blindness caused by very high fluid concluded that THC was the more effective in treating nausea and vomiting pressures within their eyes. If they resulting from radiation treatment or oth effective drug. causes. No legitimate studies have been experiment with marijuana to lower A librarian can help locate copies of conducted which make such conclusions their eye fluid pressure. it can cause thes studies should you want to see dramatic drops in their blood pressure them for yourself. Sallan. et al.. Doctor Richard J. Gralla. a profes' and reduce the blood supply to their "Antiemetic Effect of Delta-9- of medicine at Cornell University heads. Glaucoma experts testified this Tetrahydrocannibinol in Patients Medical College. an associate atten reduced the blood supply to the optic Receiving Cancer Chemotherapy." 293 physician at the Memorial Sloan- nerves and could speed up. rather than New England Journal of Medicine 795- Kettering Cancer Center. and an ex. slow down. their loss of eyesight. 797 (1975): Chang. et al_ "Delta-9- in cancer research. testified: MS. glaucoma and cancer patients Tetrahydrocannabinol as an Antiemetic Most experts would say. and our stud who have undiagnosed heart problems in Cancer Patients Receiving High-Dose support. that the cannabinoide in genera risk heart palpitations. very rapid heart Methotrexate," 91 Annais of Internal not very effective against the major caur beats and sudden dramatic drops in Medicine 819-824 (1979): Levill et ai. nausea and vomiting. Federal Register / Vol. 57, No. 59 / Thursdav. March 26. 1992 / Notices 10: Doctor Gralla added: Glaucoma." 87 Ophthalmology 222-228 Doctor George Spaeth is the Direct I have found that because of the negative (1980) of the Glaucoma Service at Wills Eye side effects and problems associated with Unusally large doses or marijuana Hospital in Philadelphia. the largest marijuana most medical oncoiogists were needed in these three studies to service in the United States devoted and researchers have little interest in achieve the desired effect. Heavy researching and treating glaucoma a: manyuana for the treatment of nausea and marijuana use produces dizziness. to teaching other doctors about this vomiting in their patients. trouble with thinking. impaired motor disease. Doctor Spaeth is President C Doctor John Laszlo. Vice President of skills. fatigue and sleepiness. The 1976 the American Glaucoma Society. He Research for the American Cancer study by Doctors Hepler. Frank and professor of ophthalmology. the edito Society. an expert who has spent 37 Petrus emphasized "Our subjects were a scholarly eye journal (Ophthalmic years researching cancer treatments. sometimes too sleepy to permit Surgery). and the author of over 200 and who has written a leading textbook measurement of intraocular pressures research articles on glaucoma. He on the subject. "Antiemetics and Cancer 3 hours after intoxication." If a testified: Chemotherapy." testified there is not glaucoma patient were to smoke I have not found any documentary enough scientific evidence to justify marijuana 8 to 10 times every day for evidence which indicates that a single pa using marijuana to treat nausea and the rest of his life. would he be alert and has had his or her natural history of the vomiting. Not one nationally-recognized energetic enough to live a relatively disease altered by smoking marijuana. cancer expert could be found to testify normal life? Would he develop other on marijuana's behalf. diseases? No scientific studies exist to Amputees and victims of MS can To be an effective treatment for answer these questions. Robert Randall suffer from extreme muscle spasms. glaucoma. a drug must: (i) Lower the claims to have saved his sight by claimed marijuana is useful in treati pressure within the eye (intraocular smoking 8 to 10 marijuana cigarettes spasticity. Three unusually small. pressure). (ii) for prolonged periods of every day. Under oath he admits he inconclusive studies have tried using time. and (iii) actually preserve sight stars at home most days. follows no pure THC. not marijuana. to treat Ivisual fields). Five scientific studies are daily schedule or routine. and has not spasticity. D.J. Petro and C. Ellenber cited as evidence marijuana IS an held a regular job in over 15 years. He "Treatment of Human Spasticity wit effective glaucoma treatment. Those also has avoided having a Delta-9-Tetrahydro-cannabinol. 21 who cite these studies are mistaken comprehensive medical examination Journal of Clinical Pharmacology 41: These studies tested pure THC. not since 1975. 416S (1981) (included only nine marijuana. W.D. Purnell and J.M. Cregg. patients). Two of the studies are me: No scientific studies have shown "Delta-9-Tetrahydorcannabinol. abstracts. or short digests. without r marijuana can reduce eye pressure over Euphoria and Intraocular Pressure in detail. Hanigan. Destee & Troung Al long periods of time. Man." 7 Annals of Ophthalmology 921- B45. Clin. Pharmacol. Ther. 198 (198 No scientific studies have shown 923 (1975): M. Perez-Reyes. D. Wagner. (included only five patients). and M.E. Wall. and K.H. Davis. "Intravenous marijuana can save eyesight. Sandyk. Cannoe. Stern and Snider Administration of Cannabinoids on America's top glaucoma experts reject Abstr. PP 331. 36 Neurology 342 (198 Intraocular Pressure." The marijuana as medicine. Doctor Keith (included only three patients). Pharmacology of Marijuana 829-832 Green is a professor of Ophthalmology No scientific studies exist which 1 (M.C. Braude and S. Szara eds. 1976): who serves. or has served. on the marijuana to relieve spasticity. J.C. Merritt. S.M. McKinnon. J.R. editorial boards of eight prestigious eye National experts on MS reject Armstrong. G. Hatem. and L.A. Reid. journals (Ophthalmic Research. Oftalmo marijuana as medicine. Doctor Ken: "Oral Delta-9-Tetrahydrocannabinol in Abstracto. Current Eye Research. P. Johnson is Chariman of the Hyperogeneous Glaucomas." 12 Annals Experimental Eye Research. Department of Neurology at the of Ophthalmology 947 (1980): K. Green Investigative Opthalmology. American University of Maryland School of and M. Roth. "Ocular Effects of Topical Journal of Ophthalmology. Archives of Medicine. He manages that Marylar Administration of Delta-9- Ophthalmology. and Survey of Center for MS. one of the most activ Tetrahydrocannabinol in Man." 100 Ophthalmology). Doctor Green has MS research and treatment centers conducted extensive basic and clinical Archives of Ophthalmology 265-267 the United States. He sits on the (1982): and WM. Jay and K. Green. research using marijuana and THC to editiorial boards of noted medical Multiple-Drop Study of Topically treat glaucoma patients. He has journals related to MS (Neurology a Applied 1% Delta-9- authored over 200 books or research Journal of Neuroimmunology). He is Tetrahydrocannabinol in Human Eyes." articles in ophthalmology and is a highly author of over 100 scientific and me 101 Archives of Ophthalmology 591-593 respected expert on this subject. Doctor articles on MS. Doctor Johnson has Green testified: (1983). spent most of his long career Threee studies show very heavy doses There is no scientific evidence that researching MS and has diagnosed of marijuana. taken for short periods of indicates that marijuana is effective in treated more than 6.000 patients wir time. can reduce eye pressure. R.S. regulating the progression of symptoms MS. Doctor Johnson testified: Hepler. I.M. Frank. and T.J. Ungerleider. associated with glaucoma. It is clear At this time. I am not aware of "Pupillary Constriction After Marijuana that there is no evidence that marijuana use legtimate medical research in which Smoking. 74 American Journal of prevents the progression of visual loss in marijuana was used to treat the sympto Ophthalmology 1185-1190 (1972): R.S. glaucoma. The quantities of the drug multiple sclerosis. To conclude th. Hepier. I.M. Frank. and R. Petrus. required to reduce intraocular pressure in marijuana IS therapeutically effective W "Ocular Effects of Marijuana Smoking." glaucoma sufferers are large. and would conducting rigorous testing would be require the inhalation of at least six The Pharmacology of Marijuana 815-824 professionally irresponsible. marijuana cigarettes each day. (1976): and J.C. Merritt. W.J. Crawford. Smoking is not a desirable form of treatment Doctor Stephen Reingold is Assis P.C. Alexander. A.L. Anduze and S.S. for many reasons [M]arijuana has Vice President of Research for the Gelbart. "Effect of Marijuana on little potential future as a glaucoma National Multiple Sclerosis Society Intraocular and Blood Pressure in medication. which spends over $7 million each 10502 Federal Register / VoL 57. No. 59 / Thursday. March 26. 1992 / Notices on MS research. Only the Federal sight yet be has taken standard testing. Weinberger V. Hynson. Etc. Government spends more. Doctor glaucoma drugs continuously since 1972 U.S. 609. 639: Reingold testified: There is DO objective way to tell from [Mapressions or beliefs of physicians. I could find no actual published research these stories whether it is marijuana matter how fervently held. are treachere which has used marijuana la the that is helpful. or the proven. traditional existing research using THC. the results were medicines. Even these users can never Nearly half the doctors who testif inconclusive In the absence of any know for sure for NORML are psychiatrists. They well-designed. well-controlled research Third. any mind-altering drug that not specialize in treating or research the National Multiple Sclerosis Society produces euphoria can make a sick cancer. glaucoma or MS. One is a does not endorse or advocate its use person think he feels better. Stories from general practitioner who works as a patients who claim marijuana helps wellness counselor at a health spa. Doctor Donald H. Silberberg is them may be the result of the mind- Under oath he admits to using every Chairman of the Department of altering effects of the drug. not the illegal. mind-altering drug he has ev Neurology at the University of results of improvements in their studied. and he prides himself on Pennsylvania School of Medicine and conditions. recommending drugs that would ne' Chief of the Neurology Service at the Fourth. long-time abusers of be recommended by medical school Hospital of Pennsylvania. Doctor marijuana are not immune to illness. reputable physicians. Another is a Silberberg is on the editorial board of Many eventually get cancer. glaucoma. general practitioner who quit practi Annals of Neurology and is President of MS and other diseases. People who in 1974. He admits he has not kept 1 the National Medical Advisory Board become dependent on mind-altering new medical and scientific informa. for the National Multiple Sclerosis drugs tend to rationalize their behavior. about marijuana for 18 years. Society. He has been actively They invent excuses. which they can Only one of the doctors called by researching and treating MS for most of come to believe. to justify their drug NORML is a nationally-recognized his career. has written over 130 medical dependence. Stories of marijuana's expert. Doctor John C. Merritt is a articles on MS and is Co-Director of a benefits from sick people with a prior board-certified ophthalmologist an large MS research center at the history of marijuana abuse may be researcher who has authored articl University of Pennsylvania. Doctor based on rationalizations caused by the use of marijuana and cannabine Silberberg testified: drug dependence. not on any medical to reduce eye pressure. He is in pri- I have not found any legitimate medical or benefits caused by the drug. Robert practice and sees mostly children scientific works which snow that marijuana Randail. for example. admits under oath suffer from glaucoma. Doctor Mem is medically effective LD treating to becoming a regular user in 1968. four testified. "[M]arijuana is a highly multiple sclerosis or spasticity. The years before he showed the first signs effective IOP-lowering drug which long-term treatment of the symptoms of of. and was diagnosed as having. multiple scierosis through the use of be of critical value to some glaucar glaucoma. Since then he has smoked marijuana could be devastating. [T]he patients who. without marijuana. P use of (marysana). especially for long-term marijuana 8 to 10 times every day. progressively go blind." The last treatment would be worse than the A century ago many Americans relied scientific study using marijuana in original disease itself. on stories to pick their medicines. glaucoma patients. published by D especially from snake oil salesmen. The only favorable evidence that Mernal in 1979. concluded: Thanks to scientific advances and to the could be found by NORML and DEA passage of the Federal Food. Drug and It IS because of the frequency end Be consists of stories by marijuana users with which the untoward events OCCURT Cosmetic Act (FDCA) in 1906. 21 U.S.C. who claim to have been helped by the that marijuana inhalation is not an idea 301 et seq.. we now rely on rigorous drug. Scientists call these stories therapeutic modality for glaucoma pati scientific proof to assure the safety and anecdotes. They do not accept them as effectiveness of new drugs. Mere stories One year later. in 1980. Doctor N reliable proofs. The FDA's regulations. are not considered an acceptable way 10 gave the following testimony. unde for exampie. provide that in deciding judge whether dangerous drugs should oath. before the United States Con whether a new drug is a safe and be used as medicines House Select Committee on Name: effective medicine. "isolated case There are doctors willing 10 testify Abuse and Control: reports will not be considered." 21 that marijuana has medical uses For me to sit here and say that the to CFR 314.126(e). Why do scientists NORML found over a dozen to tesufy in pressure effects occurred repeatedly. d consider stories from patients and their this case. We have a natural tendency to and day out I have no data. and neithe doctors to be unreliable? believe doctors. We assume their anyone else. and that IS the real crux σ First. sick people are not objective opinions are entitled to respect But natter. When we are talking about tree scientific observers. especially when If what if a docto' is giving an opinion disease like glaucoma. which LS a chron comes to their own health We all have beyond his professional competence? disease. the real issue IS. does the man heard of the placebo effect. Patients Evaluating the safety and effectiveness repearediv lower the intraocular prease have a tendency to respond to drugs as have shown you no studies. and of drugs is a specialized area Does the they believe is expected of them. knowledge there is no data to that effe doctor have this specialized expertise? Imagine how magnified this placebo Is he familiar with all the published Doctor Merritt was unable to ex effect can be when a suffering person scientific studies? Or is he improperly under oath. the contradictory posi experiments on himself. praying for basing his opinion on mere stories or he has taken on this subject. some relief. Many stories no doubt are anecdotal evidence? Does be really Each of NORML's doctors testifi due to the placebo effect. not to any real know what he is talking about? Does he opinion is based on the published medical effects of manjuana. have a personal motive to exaggerate as scientific studies. With one except Second. most of the stories come from lie? Questions like these led the United none of them could identify under people who took marijuana at the same States Supreme Court. in 1973. to warn the scientific studies they swore th time they took prescription drugs for about the opinions of doctors concerning relied on Only one had enough their symptoms. For example, Robert the value of drugs as medicine. when knowledge to discuss the scientific Randall claims marijuana has saved his not supported by rigorous scientific technicalities involved. Eventually Federal Register / Vol. 57. No. 59 / Thursday. March 26. 1992 / Notices 1050 one admitted he was basing his opinion began away from anecdotal evidence to "grandfathered" drugs. They need not on anecdotal evidence, on stories he objectively conducted scientific meet modern standards for safety and heard from patients. and on his research. away from uninformed effectiveness. impressions about the drug. opinions of lay persons and local A fifth group of drugs was accepted Sadiy. Doctor Ivan Silverberg. an doctors to expert opinions of specialists for research use only. not for use in oncologist from San Francisco, trained to evaluate the safety and treatment of patients. 21 U.S.C. 355(i) exaggerated while on the witness stand. effectiveness of drugs. and away from (so-called "IND or approved At first he swore "there is voluminous totally democratic decision-making to investigational new drugs") medical research which shows oversight by the Federal Government. Drugs intended for medical use and marijuana is effective in easing nausea By 1969. Congress had developed shipped interstate are subject to Feder and vomiting." Pushed on cross- detailed Federal statutory criteria under seizure under the FDCA if they do not examination to identify this voluminous the FDCA to determine whether drugs within one of the above accepted sets research. Doctor Silverberg replied. are acceptable for medical use. Those groupings. It seems fair to say that "Well I'm going to have to back deemed acceptable can be marketed seizable drugs were rejected by off a little bit from that." How far would nationally. Those deemed unacceptable Congress for medical uses. Doctor Silverberg back off? Was he are subject to Federal seizure if in enacting the Controlled Substanc aware. at least, of the approximate marketed interstate. The FDCA is a very Act in 1970. could Congress have number of scientific studies that have complex regulatory scheme not easily intended to create a totally new Feder been done using marijuana to treat summarized. However, it is fair to say standard for determining whether dru: nausea? Under oath. he replied. "I would that drugs falling into one of four FDCA have accepted medical uses? Or did doubt very few. But. no. I'm not." categories were accepted by Congress Beyond doubt. the claims that Congress intend to rely on standards for medical use. had developed over the prior 64 years marijuana is medicine are false, First. Congress accepted new drugs dangerous and cruei. under the FDCA? There is nothing in which have been approved by FDA's Controlled Substances Act. its Sick men. women and children can be experts as safe and effective for use in fooled by these claims and experiment legislative history. or its purposes tha treatment. based on substantial with the drug. Instead of being helped. would indicate Congress intended to scientific evidence. 21 U.S.C. 321(p) and they risk serious side effects. If they depart radically from existing Federa 355 (so-called "NDA-approved drugs"). law. neglect their regular medicines while Second. Congress accepted those trying marijuana, the damage could be drugs "generally recognized, among Indeed. it seems likely that the core irreversible. It is a cruel hoax to offer experts qualified by scientific training standards developed under the FDCA false hope to desperately ill people. and experience to evaluate the safety represent a long-term consensus of Those who insist marijuana has and effectiveness of drugs. as safe and expert medical and scientific opinion medical uses would serve society better effective," based on substantial conterning when a drug should be by promoting or sponsoring more scientific evidence. 21 U.S.C. 321(p) and accepted by anyone as safe and legitimate scientific research. rather effective for medical use. 355: Weinberger V. Bentex than throwing their time. money and Pharmaceuticals, Inc.. 412 U.S. 645 Fortunately. there is a way to rhetoric into lobbying. public relations (1973). An acronym for this category is corroborate what Congress intended. campaigns and perennial litigation. "human GRASE drugs" (Generally Congress did more than just announc Clarification of Currently Accepted Recognized As Safe and Effective). criteria for scheduling drugs of abuse under the Controlled Substances Act. Medical Use These drugs achieve acceptance through rigorous scientific proof. through a past Congress applied those criteria to an The Controlled Substances Act of history of widespread use in treatment initial listing of drugs that it placed in 1970 divides the universe of all durgs of in the United States. and through the original five schedules of the Act abuse into five sets or schedules. Drugs recognition by a consensus of drug NDA-approved drugs were placed in Schedule I are subject to the most experts outside the FDA. Congress into Schedules II. III. IV an severe controis, because they have a Third. Congress accepted for use in of the Act. For example, pethidine (a high potential for abuse and no currently veterinary medicine those drugs known as meperidine) received New accepted medical use in treatment in the "generally recognized. among experts Drug Application (NDA) approval in United States. 21 U.S.C. 812 (b)(1). Drugs qualified by scientific training and 1942 Congress put it into Schedule of abuse which have currently accepted experience to evaluate the safety and II(b)(14). Methamphetamine had an medical use in treatment in the United effectiveness of animal drugs. as safe approved NDA. Congress put it into States are placed in Schedules II. III. IV and effective." based on substantial Schedule III(a)(3). I am not aware of and V. Regrettably. the Controlled scientific evidence. 21 U.S.C. 321(w) and drug with an approved NDA that Substances Act does not speak directly 355. An acronym for these is "animal Congress originally put into Schedule to what is meant by "currently accepted GRASE drugs." They achieve Drugs with medical uses, but with medical use." acceptance through rigorous scientific approved NDA's also were placed by A century before the Controlled evidence and through recognition by a Congress into Schedules II. III. IV an Substances Act was enacted. the consensus of drug experts outside the For example. cocaine was put into determination of what drugs to accept FDA. Unlike human GRASE drugs. Schedule ll(a)(4). Codeine combinati as medicine was totally democratic and animal GRASE drugs need not have a were put into Schedules III(d)(1) and totally standardless. Each patient and past history of widespread use. Morphine combinations were put int each physician was free to decide for Finally. Congress accepted those Schedule III(d)(8). Phenobarbital wa himself. often based on no more than drugs marketed prior to 1938 which had put into Schedule IV(11). Barbiturate anecdotal evidence. This state of affairs been subject to the 1906 provisions of were put into Schedule III(b)(1). became unsatisfactory to a majority of the FDCA. provided these very old drugs Amphetamines were put into Sched the American people. in 1906. Congress retain their exact formulations and are III(a)(1). intervened with the passage of the Food. never promoted for new uses. 21 U.S.C. The Court of Appeals for the First Drug and Cosmetic Act (FDCA). A shift 321(p) and (w). These are politically Circuit was correct when it decided 10504 Federal Register / Vol. 57, No. 59 / Thursday. March 26. 1992 / Notices Grinspoon V. DEA. 828 F.2d 881 (1987) 8. Recognition and use of the substance by risks. there must be adequate stuc that NDA approval is not the only a substantial segment of the medical all methods reasonably applicable method by which drugs can achieve practitioners in the United States. show the pharmacological and Federal recognition as having medical Some uncertainty remains over the toxicological effects of the drug. 2 uses. Congress put both GRASE drugs precise meaning and application of parts 314.125(b)(2). This includes anima and pre-1938-grandfathered drugs into of this test. Therefore. the Court of studies and clinical trials in large Schedules II. III. IV and V of the CSA. Appeals for the District of Columbia numbers of humans. 21 CFR 312.21 Drugs recognized under the FDCA for Circuit remanded these proceedings for studies need not be well-controlle research use only. not for use in a further explanation. In addition to they must be adequate. Edison treatment. such as alphacetylmethadol addressing those parts of the test that Pharmaceuticals Co. V. FDA. 600 and marijuana. were placed by Congress concerned the Court of Appeals. it 837 (D.C. Cir. 1979). Short term (ac into Schedule 1. would be useful to clarify the entire test. studies of a drug intended to treat Unfortunately, Federal records are not pinpoint its origins. and identify which term (chronic) illnesses. such as complete enough to do a comprehensive elements are both necessary and glaucoma or MS. are clearly inade mathematical mapping. tracing every sufficient to establish a prima facie case United States V. Naremco. Inc.. 55 drug in the initial Controlled Substances of currently accepted medical use. This 1138. 1143 (8th Cir. 1977). The seco Act schedules back to its legal status is not an effort to change the substantive element of our eight-point test. na under the FDCA. Nevertheless. law. The statutory meaning of currently "the toxicology and pharmacolog determining legislative intent does not accepted medical use remains the same substance in animals." should be require mathematical certainty. as enacted by Congress in 1970. My clarified as follows: Probability based on circumstantial purpose simply is to clarify this evidence, on samplings. and on Agency's understanding of the law. There must be adequate pharmacoi and toxicological studies. done by all inductive reasoning can suffice. A The Drug's Chemistry Must Be methods reasonably applicable. on th especially when there is nowhere else to Known and Reproducible of which it could fairly and responsib turn. concluded. by experts qualified by SC The pattern of initial scheduling of The ability to recreate a drug in training and experience to evaluate 1: drugs in the Controlled Substance Act. standardized dosages is fundamental to and effectiveness of drugs. that the st viewed in light of the prior legal status testing that drug and to using it as a is safe for treating a specific. recogni: of these drugs under the FDCA. medicine. Knowing the composition. disorder. properties. methods of production. and convinces me that Congress equated the It must be emphasized that wh term "currently accepted medical use in methods of analysis of a drug is existence of adequate safety test essential to reproducing it in treatment in the United States" as used separate analytical question. the in the Controlled Substances Act with standardized dosages. To be GRASE or ultimate determination of wheth the core FDCA standards for acceptance to receive NDA approval. a drug's drug is safe for a specific use is Γ. of drugs for medical use. chemistry must be known and distinct issue. Safety and effectiv reproducible. See e.q.. 21 CFR This is not to say that every FDCA are inextricably linked in a risks 314.50(d)(1) and 314.126(b)(7)(d): Dorovic requirement for GRASE status. or for benefits calculation. A determina V. Richardson. 749 F.2d 242. 251 (7th Cir. NDA approval. is pertinent to that a drug is ineffective is tantar 1973). The listing of a drug in a current scheduling determinations under the to a determination that it is unsa edition of one of the official compendia Controlled Substances Act. There are United States V. Rutherford. 442 normally satisfies this requirement. 21 differences. But the core FDCA criteria (1970). U.S.C. 321(j): 21 CFR 314.50(d)(1). appear to have guided the Congress in The first element of our eight-point The scheduling criteria of the the decisions it made concerning the test. namely. "scientifically determined Controlled Substances Act appe initial scheduling of drugs in the Act. treat the lack of medical use and and acccepted knowledge of its These same core FDCA criteria served chemistry." should be clarified to read: safety as separate consideration: as the basis for an eight-point test used rulings of this Agency purported The substance's chemistry must be by my predecessor as Administrator to safety as a distinct factor. 53 FR scientifically established to permit it to be describe drugs with currently accepted (February 22. 1988). In retrospect reproduced into dosages which can be medical uses. 54 FR 53783 (December 29. inconsistent with scientific realit standardized. The listing of the substance in 1989): a current edition of one of the official Safety cannot be treated as a sep compendia. as defined by section 201(i) of the analytical question. 1. Scientifically determined and accepted Food. Drug and Cosmetic Act. 21 U.S.C. knowledge of its chemistry: 321(j). is sufficient generally to meet this C There Must Be Adequate and 2 The toxicology and pharmacology of the requirement. Controlled Studies Proving Effice substance in animals: 3. Establishment of its effectiveness in Acceptance of this knowledge will be Since 1962. Congress has prohi humans through scientifically designed discussed elsewhere. the FDA to approve an NDA unle clinical trials: applicant submits adequate. well B. There Must Be Adequate Safety 4. General availability of the substance and contolled. well-designed. well- Studies information regarding the substance and its conducted. and well-documentec use: No drug can be considered safe in the studies. performed by qualified 5. Recognition of its clinical use in abstract. Safety has meaning only when investigators. which prove the ef generally accepted pharmacopeia. medical judged against the intended use of the of a drug for its intended use. 21 references. jounals or textbooks: drug. its known effectiveness. its known 355(d): 21 CFR 314.126. Similarly. 6. Specific indications for the treatment of and potential risks. the severity of the cannot be considered GRASE un recognized disorders: illness to be treated. and the availability is supported by this same quanti 7. Recognition of the use of the substance of alternative therapies. Hess & Clark quality of scienfitic proof. 21 CFI by organizations or associations of Division of Rhodia. Inc. V. FDA. 495 F.2d 314.200(e)(i): Weinberger V. Hyns physicians: and 975. 993 (D.C. Cir. 1974). To know the Etc.. 412 U.S. 609. 629 (1973). Federal Register / Vol. 57, No. 59 1. Thursday, March 26. 1992 ! Notices 105 Studies involving related. but not requirements in the FDCA since 1938. the Controlled Substances Act does no identical. drugs are irrelevant. United the only body of opinion that counts is authorize the Attorney General. nor b States v. Articles of Food & Drug. 518 that of experts qualified by scientific delegation the DEA Administrator. to F.2d 743. 747 (5th Cir. 1975). Studies training and experience to evaluate the make the ultimate medical and policy involving the same drug combined with safety and effectiveness of drugs. 21 decision as to whether a drug should ! other drugs are irrelevant. United States U.S.C. 321 (p) and (w). used as medicine. Instead. he is limite V. Articles of Drug Promise From this. one would conclude that to determing whether others accept a Toothpaste. 626 F.2d 564. 570 (7th Cir. expert acceptance of a drug as safe and drug for medical use. Any other 1987). Incomplete studies are effective for its intended use is essential construction would have the efect of insufficient. United States V. Articles of to a drug having a currently accepted reading the word "accepted" out of th Food & Drug. supra. Uncontrolled medical use under the CSA. How statutory standard. Since Congress studies are insufficient. 21 U.S.C. 355(d): widespread must this expert acceptance recognized NDA-approved drugs as Cooper Labs V. FDA. 501 F.2d 772, 778 be? having currently accepted medical use (D.C. Cir. 1974). Statistically To be GRASE. a drug must be without any need for a national insignificant studies are insufficient. 21 "generally recognized" among experts consensus of experts. FDA acceptanc CFR 312.21. 314.50(d)(6) and as safe and effective for its intended of a drug through the NDA process 314.126(b)(7). Poorly designed studies use. The drug must be known or familiar would seem to satisfy the Controlled are insufficient. 21 CFR 314.126(b)(2). to the national community of relevant Substances Act. And. since Congress Poorly conducted studies are experts. United States V. Articies of recognized GRASE drugs as having insufficient. 21 CFR part 58-Good Drug* "Furestrol Vaginal currently accepted medical uses. Laboratory Practices. Poorly Suppositories. 294 F. Supp. 1307, 1309 without the need for NDA approval. documented studies are insufficient. 21 (N.D. Ca. 1968) off'd. 415 F.2d 390 (5th acceptance of a drug by a national CFR 312.58 and 314.200(e)(4). Studies by Cir. 1969). To determine if a drug is consensus of experts also would seer investigators who are not qualified. both known to the community of experts. satisfy the Act. to conduct and to evaluate them are courts have looked to whether there is widely available scientific literature When a drug lacks NDA approval insufficient. 21 U.S.C. 355(d). Moreover. about the drug. Premo Pharmaceutical is not accepted by a consensus of since scientific reliability requires a double examination with similar results. Laboratories. Inc. V. United States. 629 experts outside FDA. it cannot be fou one valid study is insufficient. There F.2d 795. 803 (2d Cir. 1980), whether it is by the Attorney General or his delega must be two or more valid studies which widely taught in medical schools. to have a currently accepted medical corroborate each other. See 1]. Lemmon Pharmaceuticals Co. V. use. To do so would require the O'Reilley "Food and Drug Richardson. 319 F. Sup. 375, 378 (E.D. Pa. Attorney Genral to resolve complex 1970). and whether it is widely scientific and medical disputes amon Administration" 13-55 n.12 (1985). discussed by experts. United States V. experts. to decide the ultimate medic Lay testimonials. impressions of policy question. rather than merely physicians. isolated case studies. Bentex Ulcerine. 469 F. 2d 875. 880 (5th random clinical experience. reports 80 Cir. 1972). determine whether the drug is accept lacking in details they cannot be The recognition of a drug as GRASE by others. scientifically evaluated. and all other need not be universal. General Because the recognition of a drug 1 forms of anecdotal proof are entirely recognition is sufficient. United States V. non-experts is irrelevant to GRASE irrelevant. 21 CFR 314.126(e): 41 Cartons* *Ferro-Lac. 420 F.2d 1126. status. to NDA approval. and to Weingerger V. Hynson. Etc.. 412 U.S. 1132 (5th Cir. 1970). The Supreme Court currently accepted medical use unde 609. 630 (1973). has interpreted this to mean a consensus the Controlled Substances Act. point Element three of our eight-point test. of experts is familiar with and accepts a seven and eight of our eight-point tes drug as safe and effective. Weinberger should be combined and restated as namely. "establishment of its effectiveness in humans through V. Hynson. Etc.. 412 U.S. 609. 629 (1973). follows: scientifically designed clinical trials." However. if there is a serious dispute The drug has a New Drug Application should be restated as: among the experts. a drug cannot be (NDA) approved by the Food and Drug considered GRASE. United States V. An Administration pursuant to the Food. Dru There must be adequate. well-controlled. Article of Food Coco Rico. 752 F.2d and Cosmetic Act. 21 U.S.C. 355. Or. a well-designed. well-conducted and well- 11. 15 (1st Cir. 1985): Merrit Corp. V. consensus of the national community of documented studies. including clinical Folsom. 165 F. Supp. 418. 421 (D.D.C. experts. qualified by scientific training ar investigations. by experts qualified by 1958). experience to evaluate the safety and scientific training and experience to evaluate the safety and effectiveness of drugs. on the During the NDA process. the FDA effectiveness of drugs. accepts the safety effectiveness of the substance for use in basis of which it could fairly and responsibly may reach out to the expert community treating a specific. recognized disorder. i. be concluded by such experts that the for its views. 21 CFR 314.103(c)(3). The material conflict of opinion among exper: substance will have the intended effect in FDA need not determine that a drug is preciudes a finding of consensus. treating a specific. recognized disorder. generally known and accepted by the D. Acceptance by Qualified Experts Is expert community. Nor must the FDA This restatement also incorporates Required develop a consensus of opinion among component of part one of our eight-p outside experts. The FDA has both the test concerning "accepted knowledg The opinions of lay persons are totally experts and the statutory mandate to its chemistry." irreievant to whether a drug is GRASE resolve conflicts over the safety and or meets NDA requirements. The E. The Scientific Evidence Must Be efficacy of new drugs. Weinberger V. observations and opinions of medical Widely Available Bentex Pharmaceuticals. Inc.. 412 U.S.C practioners who are not experts in 638. 653 (1973). Nothing in the FDCA. nor in FDA evaluating drugs also are irrelevant to In drafting the Controlled Substances regulations. requires that scientific whether a drug IS GRASE or meets NDA Act. Congress appears to have evidence supporting an NDA be requirements. Weinberger V. Hynson. accommodated. rather than chosen from published. This stems from the fact I Etc.. 412 U.S. 609. 619 (1973). By explicit these different FDCA standards. Clearly, a consensus of experts outside FDA 10506 Federal Register / Vol. 57. No. 59 / Thursday. March 26. 1992 / Notices not required for NDA approval. In As the Court of Appeals points out. compendia. as defined by section 201 contrast. most courts have held that a requiring a material history of past use Food. Drug and Cosmetic Act. 21 U.S drug cannot be considered GRASE in treatment before recognizing a drug 321(i). is sufficient generally to meet unless the supporting scientific evidence as having a currently accepted medical requirement. appears in the published scientific and use. would permanently freeze all (ii) There Must Be Adequate Safety medical literature. Without published Schedule I drugs LETER Schedule I. 930 studies. it would be difficult for the There must be adequate pharmacc F.2d at 940. Clearly. Congress did not community of experts outside FDA to and toxicological studies done by ali intend this result Moreover. the use of reasonably applicable on the basis 0 develop an informed acceptance of a the word "currently" before the term it couid fairly and responsibly be con drug for medical use. Cooper Labs Inc. v. "accepted medical use" would indicate by experts qualified by scientific trai FDA. 501 F.2d 772. 786 (D.C. Cir. 1974). Congress rejected the human GRASE experience to evaluate the safety an Point four of the eight-point test requirement of past material use in effectiveness of drugs. that the subst focuses. in part. on the "general treatment. I conclude that the general safe for treating a specific. recognize disorder. availability of information regarding the availability of a drug is irrelevant to substance and its use." This should be whether it has a currently accepted (iii) There Must Be Adequate and W. clarified to read: medical use in treatment within the Controlled Studies Proving Efficacy In the absence of NDA approval. meaning of the Controlled Substances There must be adequate. well-con: information concerning the chemistry. Act. well-designed. well-conducted and V pharmacology. toxicology and effectiveness documented studies. including clinic G. Recognition in Generally Accepted of the substance must be reported. published. investigations. by experts qualified t Texts Is Irreievant scientific training and experience to or otherwise widely available. in sufficient Point five of the eight-point test deals the safety and effectiveness of drugs detail to permit experts. qualified by scientific training and experience to evaluate with "recognition of its clinical use in basis of which it could fairly and res be concluded by such experts. that 1 the safety and effectiveness of drugs. to fairly generally accepted pharmacopeia. substance will have its intended eff and responsibly conclude the substance IS medical references, journals or treating a specific. recognized disoro sate and effective for use in treating a textbooks.' The fisting of a drug in an specific. recognized disorder. official compendium is sufficient to (iv) The Drug Must Be Accepted by Experts F. General Availability 0' a Drug Is show Its chemistry is scientifically Irrelevant established. This appears in my The drug must have a New Drug clarification to point one. The Application (NDA) approved by the Drug Administration. pursuant to the The second component of point four of requirement that information concerning Drug and Cosmetic Act. 21 U.S.C. 35 the eight-point test involves the the chemistry. pharmacology. toxicology consensus of the national communit "general availability of the substance" and effectiveness of the substance be experts. qualified by scientific train for use in treatment. The second reported. published or otherwise widely experience to evaluate the safety an component of point eight focuses on available. is explained adequately in effectivenss of drugs. must accept it "use of the substance by a substantial revised point four. To the extent the and effectiveness of the substance o segment of the medical practitioners in scheduling of a drug directly influences treating a specific. recognized disoro the United States." These elements its recognition in publications. this material conflict of opinion among e justifiably concerned the Court of precludes a finding of consensus. element is subject to the same criticism Appeals. leading to the remand in this identified by the Court of Appeals (v) The Scientific Evidence Must Be Available case. concerning point four. Therefore. this Under the FDCA. a human GRASE should not be treated as a distinct In the absence of NDA approval. drug must have a material history of requirement. information concerning the chemistr pharmacology. toxicology and effect past use in treatment in the United H. Specific Recounized Disorders Are of the substance must be reported. F States. 21 U.S.C. 321(p)(2) (which has the Referent or otherwise widely available in sul otherwise than in such detail to permit experts. qualified by investigations. been used to a material II is impossible to judge the safety and scientific training and experience to extent or a material time): Weinberger effectiveness of a drug except in relation the safety and effectiveness of drug: 1. Hynson. Etc.. 412 U.S. 609. 631 (1973). to a specific intended use. A drug cannot and responsibly conclude the substa Rigorous scientific proofs and current obtain NDA approval or GRASE status safe and effective for use in treating enanimous acceptance by the medical except in relation to the treatment of a specific. recognized disorder. and scientific community are not enough specific. recognized disorder. This is an Together these five elements for a human drug to be GRASE. Tri-Bio essential aspect of whether a drug has constitute prima facie evidence Labs. Inc. V. United States. 836 F.2d 135. currently accepted medical use. Rather drug has currently accepted me 142 n.8 (3d Cir. 1987). The general than standing alone. this requirement in treatment in the United States availability of a drug for use in will be more clearly understood by interest of total clarity. let me en treatment is a factor courts have incorporating it into the other critical those proofs that are irrelevant considered to determine if a human drug elements. determination of currently accep is GRASE. To summarize. the five necessary medical use. and that will not be In contrast. a drug can achieve current elements of a drug with currently considered by the Administrato. acceptance for human medical use accepted medical use in treatment in the United States are: (i) Isolated case reports: through the NDA process without a past (ii) Clinical impressions of practit. history of use in treatment. Also. animal (i) The Drug's Chemistry Must Be Known and drugs can become accepted as CRASE Reproducible (iii) Opinions of persons not quali scientific training and experience to without any past historv of medical use. The substance's chemistry must be the safetv and effectiveness of the 5 Given this conflict in FDCA standards. scientifically established to permit it to be at issue: which did Congress choose when reproduced into dosages which can be (iv) Studies or reports so lacking 1. drafting the CSA? standardized. The being of the substance in as to preciude responsible scientific a current edition of one of the official evaluation: Federal Register / Vol. 57. No. 59 1 Thursday. March 26. 1992 / Notices 1 (v) Studies or reports involving drug effectiveness. and the limited data how smoking or burning the plant substances other than the precise substance available on its risks. as reflected in the at issue: material affects the composition of (vi) Studies or reports involving the published scientific studies. He also these chemicals. It is not possible 1 substance at issue combined with other drug emphasized the importance of this data reproduce the drug in dosages which substances: to the conclusions reached by experts can be considered standardized by (vii) Studies conducted by persons not concerning the drze 54 FR 53783. I take currently accepted scientific criter qualified by scientific training and experience this to mean that under initial factor Marijuana is not recognized in any to evaluate the safety and effectivness of the (4)(b). he believed the information substance at issue: current edition of the official compt available to experts is insufficient for (viii) Opinions of experts based entirely on 21 U.S.C. 321(j). unrevealed or unspecified information: them responsibly and fairly to conclude Second. adequate safety studies (1x) Opinions of experts based entirely on the marijuana is safe and effective for not been done. All reasonably theoretical evaluations of safety or use as medicine. applicable pharmacological and effectiveness. Marijuana is not recognized as toxicological studies have not been medicine in generally accepted Bad Medicine By Any Standard carried out. Most of the chronic an: pharmacopeia. medical references and studies have been conducted with My predecessor as DEA Adminstrator textbooks. as noted by my predecessor. or intravenous THC. not with mari developed and relied upon an eight- 54 FR 53784. I take this to mean. under Pharmacological data on marijuan: point test to determine whether initial factor (5). that he determined that bioavailability. metabolic pathway marijuana has accepted medical uses. 54 marijuana's chemistry is neither known. pharmacokinetics in inadequate. S FR 53783 (December 29. 1989): nor reproducible. as evidenced by its in humans are too small and too fe 1. Scientifically determined and accepted absence from the official pharmacopeia. Sophisticated epidemiological stud knowledge of its chemistry: Finally. my predecessor concluded. marijuana use in large populations ! the toxicology and pharmacology of the under initial factor (8)(a). that the vast required. similar to those done for substance in animals: majority of physicians does not accept 3 Establishment of its effectiveness in tobacco use. Far too many questio marijuana as having medical use. 54 FR humans through scientifically designed remain unknown for experts fairly 53784. Along the way. he found that clinical trials: responsibly to conclude marijuana highly respected oncologists and 4. General availability of the substance and safe for any use. information regarding the substance and i!s antiemetic researchers reject marijuana for use in controlling nausea and Third. there are no adequate. Wt use: 5. Recognition of its clincial use in vomiting. 54 FR 53777. that experts controlled scientific studies provin generally accepted pharmacopeia. medical experienced in researching glaucoma marijuana is effective for anything references. journals or textbooks: medications reject marijuana for use in Fourth. marijuana is not accepte 6. Specific indications for the treatment of treating glaucoma. 54 FR 53779. and that medical use in treatment by even recognized disorders: noted neurologists who specialize in respectable minority, much less a 7. Recognition of the use of the substance treating and conducting research in consenus. of experts trained to ev: by organizations or associations of spasticity reject marijuana for use by drugs. The FDA's expert drug eval physicians: and 8. Recognition and use of the substance by MS patients, 54 FR 53780. I take this to have rejected marijuana for medic mean my predecessor found no national No NDA has been approved by FT d substantial segment of the medical consensus of qualified experts accepts marijuana. The testimony of natio: practitioners in the United States. The Court of Appeals remanded the marijuana's value as medicine. recognized experts overwhelmingi decision of my predecessor for Certainly I cannot know my rejects marijuana as medicine. predecessor's unstated reasoning. compared to the scientifically emp clarification of what role factors (4). (5) However. I have reviewed the entire testimony of the psychiatrists. a end (8) of the initial eight-point test record de novo. and I am convinced that wellness counselor and general played in his reasoning. For ease of discussion. these factors can be divided his application of the initial eight-point practitioners presented by NORM as follows: test to this record correctly resulted in Fifth. given my conclusions on F the conclusion that marijuana has no one. two and three. it follows that (4)(a) General availability of the currently accepted medical use in published scientific evidence is nc substance treatment in the United States. adequate to permit experts to fairi (4)(b) General availability of Therefore. I adopt in their entirety the responsibly conclude that marijua information regarding the substance and its findings of facts and conclusions of law safe and effective for use in huma: use: reached by the former Administrator in A failure to meet just one of the (5) Recegnition of its clinical use in generally accepted pharmacopeia. medical his final order of December 21. 1989. 54 points precludes a drug from havir references. journals or textbooks: FR 53767. currently accepted medical use. (8)(a) Recognition of the substance Pursuant to the remand of the Court of Marijuana fails all five points of th by a substantial segment of the medical Appeais. I have condensed and clarified NORML has argued. unsuccessi practitioners in the United States: and the initial standard into a five-point test. that the legal standard for current (8)(b) [U]use of the substance by a substantial segment of the medical My application of the refined. five-point accepted medical use should be W test to this record is set out briefly a respectable minority of physicia practitioners in the United States. below. accepts the drug. The key to this I have found no evidence indicating First. marijuana's chemistry is neither medical malpractice defense is th: nitial factors (4)(a) or (8)(b) played any fully known. nor reproducible. Thus far. minority opinion must be recogniz role in my predecessor's decision. In over 400 different chemicals have been respectable. as competent. by mer light of my understanding of the legal identified in the plant. The proportions of the profession. standard involved. these factors are and concentrations differ from plant to In the absence of reliable evide: irrelevant to whether marijuana has a plant. depending on growing conditions. adequately establishing marijuana currently accepted medical use. age of the plant. harvesting and storage chemistry. pharmacology. toxicolo My predecessor emphasized the lack factors. THC levels can vary from less and effectiveness. no responsible of scientific evidence of marijuana's than 0.2% to over 10%. It is not known physician could conclude that ma: 10508 Federal Register / Vol. 57. No. 59 / Thursday. March 26. 1992 ! Notices is safe and effective for medical use. To may also participate in a public meeting Waste Management and quote Doctor Kenneth P. Johnson. being derb to solicit oral comments on Decommissioning. Office of Nuclear Chairman of the Department of the proposed guidance document. Material Safety and Safeguards. U.S. Neurology at the University of Interested individuals will be given an Nuclear Regulatory Commission. Maryland. and the author of over 100 oppentunity to speak for fifteen minutes Washington. DC 20555. telephone (36 scientific and medical articles on MS: at this meeting. This time allowance 504-2568 or. Reid Rosnick. Mixed W. "To conclude that marijuana is may be extended. on request for good Coordinator. Permits and State therapeutically effective without cause. if the schedule of speakers Programs Division. Office of Solid conducting rigorous testing would be permits this extension. Waste. U.S. Environmental Protectio professionally irresponsible." DATES: The agencies will accept written Agency. 401 M Street SW.. Washingt By any modern scientific standard. comments until May 26. 1992. DC 20460. telephone (202) 260-4755. marijuana is no medicine. Individuals submitting comments after Under the authority vested in the Dated at Rockville. MD this 19th day 0: this date cannot be assured that the March. 1992. Attorney General by section 201(a) of agencies will be able to afford their the Controlled Substances Act. 21 U.S.C. For the U.S. Nuclear Regnlatory comments full consideration in any Commission 811(a). and delegated to the revisions that may be made to the Administrator of the Drug Enforcement Robert M. Bernero. proposed guidance document. Administration by regulations of the The public meeting to solicit oral Director. Office of Nuciear Material Safe Department of justice. 28 CFR 0.100tb). and Sojeguards. comments on the proposed guidance the Administrator hereby orders that document will be held on April 14. 1992. For the U.S. Environmental Protection marijuana remain in Schedule 1 as listed from 8:30 a.m. until 4:30 p.m. at the Agency. in 21 CFR 1308.11(d)(14). MayBower/Stouffer Hotel. New York Sylvia K. Lowrance. Dated: March 18. 1992. Room 1127 Connecticut Avenue NW_ Director. Office of Solid Waste. Robert C. Bonner. Washington. DC 20036. telephone (202) (FR Doc. 92-7031 Filed 3-25-92 8:45 am( Administrator. 347-3000. BILLING CODE 7590-01-M (FR Doc. 92-6714 Filed 3-25-92: e 45 ami ADDRESSES: Copies of the proposed BILLING CODE 4410-09-M guidance document may be obtained by contacting Dominick A. Orlando. NRC OFFICE OF MANAGEMENT AND Mixed Waste Project Manager. Division BUDGET NUCLEAR REGULATORY of Low-Level Waste Management and COMMISSION Decommissioning. Office of Nuclear Circular No. A-76: Performance of ENVIRONMENTAL PROTECTION Material Safety and Safeguards. U.S. Commercial Activities; Amendmen AGENCY Nuclear Regulatory Commission. Washington. DC 20555. telephone (301) AGENCY: Office of Management and Proposed Guidance Document on the 504-2566. Budget. Testing of Mixed Radioactive and Written comments on the proposed ACTION: Issuance of Transmittal Hazardous Waste guidance document should be directed Memorandum No. 11. amending OM AGENCIES: Nuclear Regulatory to David L Meyer. Chief. Regulatory Circular No. A-76. "Performance of Commission. Environmental Protection Publications Branch. Division of Commercial Activities." Agency. Freedom of Information and ACTION: Notice of availability and Publications Service. Office of SUMMARY: This notice contains request for public comment Administration. U.S. Nuclear Regulatory Transmittal No. 11. dated February Commission. Washington. DC 20555 or 1992. to OMB Circular No. i SUMMARY: The Nuclear Regulatory hand delivered to the Commission's Performance of Commercial Commission (NRC) and the offices at 7920 Norfolk Avenue. Activities." Environmental Protection Agency (EPA) Bethesda. MD between the hours of 7:45 This Transmittal Memorandum are jointly issuing a proposed guidance a.m. and 4:14 p.m. on Federal workdays. updates the Federal pay raise document on the testing of mixed Requests to speak at the public assumptions and inflation factors u radioactive and hazardous waste (mixed meeting should be submitted. in writing. for computing the Government's in- waste). This guidance document was to EPA. The written request should be house personnel and non-pay cost developed to assist mixed waste addressed to Reid Rosnick. Mixed increases for Fiscal Years 1992 thro generators in identifying and performing Waste Coordinator. Permits and State 1997. The Federal pay raise assump the testing required under the Federal Programs Branch. Office of Solid Waste and the non-pay category rates are regulations that implement the Resource (OS-342). U.S. Environmental Protection contained in the President's Budget Conservation and Recovery Act Subtitle Agency. 401 M Street SW.. Washington. Fiscal Year 1993. The factors contal C hazardous waste program and to DC 20460. Interested speakers should in OMB Circular No. A-76. Transm ensure that employee radiation include in the written request a Memorandum No. 10. dated Februa exposures are maintained As Low As statement identifying the topics to be 1991. are outdated. Reasonably Achievable (ALARA). The addressed in their presentations. the The revision does not require an: agencies are soliciting comments from names and affiliations of the agency to (1) create or maintain a interested members of the regulated individual(s) that will speak. and the duplicate control/monitoring/repor community. the States. and the public. amount of time the speaker(s) will system OF (2) adopt any additional Interested individuals may provide require. A transcript of the oral controls. not presently in complian the agencies with their comments on the proceedings will be included in the with Federal Acquisition Regulatio proposed guidance document by record for this action. (FAR). forwarding their written comments to FOR FURTHER INFORMATION CONTACT: FOR FURTHER INFORMATION CONTAC the NRC at the address listed in the Dominick A. Orlando. Mixed Waste Mr. David Childs. Federal Services "ADDRESSES" section. Interested parties Project Manager. Division of Low-Level Branch. General Management Divis JAN. -23 96(TUE) 16:16 P. 002 rederal Register / Vol. 49, No. 195 / Friday. October 5. 1984 1 Rules and Regulations 38307 ACTION Finale rule. (A) and (C) of the CSA. This allows for DEPARTMENT OF JUSTICE the Issuance of a temporary order SUMMARY: This final rule is issued by Drug Enforcement Administration controlling a substance in Schedule IV the Administrator of the Drug or V. depending upon whichever is most 21 CFR Part 1308 Enforcement Administration to appropriate to carry out the minimum temporarily place twenty-one (21) United States obligations. within the Schedules of Controlled Substances; benzodiazepine substances into Temporary Placement of Schedule IV of the Controlled time period required by paragraph 7 of article 2 of the Convention, that is. Bromazepam, Camazepam, Clobazam, Substances Act (CSA) (21 U.S.A. 801 et within 180 days after the date of the Clotiazepam, Cloxazolam, seq.). The 21 benzodiazepine substances CND communication. The findings Delorazepam, Estazolam, Ethyl are bromazepam. camazepam. pursuant to sections 261 (a). (b) and Lofiasepate, Fludiazepam, clobazam. clotiezepam. cloxezolam. Flunitrazepam, Haloxazolam, delorasepam. estaxolam. ethyl 202(b) which concern an assessment of Kelazolam, Loprazolam, loflazepate. fludiazepam. Dunitrazepam, the abuse potential for each of the 21 haloxezolem. ketezolam. loprazolam. benzodiazepines are neither established Lormetazepam, Medazapam, Nimetazepam, Nitrazepara, formetazepam. medazepam. nor required for this temporary nimetezepam. nitrazepam. nordiazepam. scheduling order. Nordiazepam, Oxazolam, Pinazepam, and Tetrazepam Into Schedule IV oxazolam, pinezepam. and tetraxepam. On Wednesday. August 1. 1984, a This temporary scheduling action is notice was published in the Federal AGENCY: Thrug Enforcement required in order for the United States to Register (40 FR 30748-9) proposing to Administration Justice. discharge its obligations under the temporarily place the 21 Convention on Psychotropic Substances. benzodiazepines into Schedule IV of the 1971. The effects of this rale will be to CSA. By this action. the United States require that the manufacture. would be in compliance with the drug distribution. dispensing security. control treaty, the Convention on registration, record keeping. reporting. Psychotropic Substances, 1871. All inventory. exportation and importation Interested persons were given until of each of the 21 benzodiazapines are August 31. 1984 to submit any comments subject to controls for Schedule IV or objections regarding the proposal. No substances. The temporary scheduling comments or objections were received order for each substance shall remain in in response to the proposal nor were effect unill the process of permanent there any requests for a hearing. scheduling. pursuant to sections 201 (a) Therefore, under the authority vested and [b] (21 U.S.C. 811 (a) and (b)) of the in the Attorney General by section CSA, is completed. 201(d)(4) (A) and (C) of the CSA (21 EFFECTIVE DATE: November 5. 1964. U.S.C. 811(d)(4) (A) and (C)) and delegated to the Administrator of the FOR FURTHER INFORMATION CONTACT: Drug Enforcement Administration by Howard McClain. Jr.. Chief. Drug regulations of the Department of Justice Control Section, Drug Enforcement (28 CFR Part 0.100). the Administrator Administration, Washington. DC 20537. hereby orders that paragraph (c) of Telephone: (202) 633-1366. I 1308.14 be amended by revising the list SUPPLEMENTARY INFORMATION of controlled substances to read as List of Subjects in 21 CFR Part 1300 follows: Administrative practice and procedure. Drug traffic control 4 1308.14 Scheckde IV. Narcotics, Prescription drugs. By notice of March 29, 1984. the (c) Secretary-General of the United Nations (1) Alprazolam 2882 advised the Secretary of State of the (2) Barbital 2145 United States that the Commission on (3) Promezepam 2748 Narcotic Drugs (CND) has decided that (4) Camazepam 2749 the above 21 benzodiazepine substances (5) Chloral betaine 2480 be added to Schedule IV of the (8) Chloral hydrate 2465 (7) Chlordiaxepaxide 2744 Convention on Psychotropic Substances, (8) Clobazam 2751 1971. (9) Clonezepam 2737 In e letter dated May 1. 1984. the (10) Clorazepate 2758 Assistant Secretary for Health. on (11) Clotiazepam 2732 behalf of the Secretary of the (12) Cloxaxwism 2753 Department of Health and Human (13) Delorazapam 2754 Services (DHHS). advised the (14) Diszepam 2785 Administrator of the Drug Enforcement (15) Estazolam US Administration that the 21 (16) Ethchlorvynel 2540 (17) Ethinamete 2545 benzodiezepines be controlled in CSA [18] Ethyl loflazepate 2758 Schedule IV, using authority provided (19) Fludiazepam 2759 by sections 201(d)(3)(B) and 201(d)(4) (20) Flunitrazepam 2783 JAN. -23' 96 (TUE) 16:17 P. 003 (21) Flurazepam 2767 since none have attained accepted (22) Halaxepam 2782 medical use in treatment status in the (23) Haloxasolam 2071 United States. as would be indicated by (24) Ketazolam 3772 (25) Loprazolam 2773 approvel of a new drug application by (26) Lorazepam 2885 the Foods and Drug Administration. (27) Lormetezepem 2774 7. Importation and Exportations. All (28) Mebutamate 2000 importation and exportation of each of (28) Medazapam 2836 the 21 benzodiazepines shall be in (30) Meprobamate 2820 compliance with Part 1312 of Title 21 of (32) Methohexital 2284 the Code of Federal Regulations. (32) Mathylphenobarbitsl (mephobarbital) 8. Criminal Liability. The 2250 (33) Niruetazepam 2837 Administrator, Drug Enforcement (34) Nitrazepam 2834 Administration. hereby orders that any (35) Nordiazepen 2838 activity with respect to each of the 21 (36) Oxazepam 2835 benzodiezepines not authorized by. or in (37) Oxazolam 2839 violation of. the Controlled Substances (38) Paraidehyde 2585 Act or the Controlled Substances Import (39) Petrichloral 2591 (40) Phenoberbital 2285 and Export Act. conducted after (43) Pinazepam 2883 (November 5. 1984) shall be unlawful. (42) Prazepam 2764 except that any person who is not now (43) Temazepam 2925 registered to handles each (44) Telrazepam 2688 benzodiazepine but who is entitled to (45) Triazolam 2887 registration under such Acts may continue to conduct normal business or Effective Dates for applicable professional practice with any of the 21 regulations: benzodiazepines between the date on All regulations applicable to each of which this rule is published and the date the 21 benzodiazepines as temporarily which the person obtains or is denied controlled substances in Schedule IV of the CSA are effective on November 5. registration provided that the application for such registration is 1984, except " otherwise provided submitted on or before November 5. below: 1. Registration Any person who 1984. manufactures. distributes. imports or Pursuant to 5 U.S.C. 605(b). the exports any of the 21 benzodiazepines Administrator certifies that the or who engages in research or conducts placement of the 21 benzodiazepines Instructional activities, must apply for into Schedule IV of the CSA will have registration by November 5. 1984. to no impact upon small businesses or conduct such activities in accordance other entities whose interests must be with Parts 1301 end 1311 of Title 21 of considered under the Regulatory the Code of Federal Regulations. Flexibility Act (Pub. L 96-354). This 2. Security. Each of the 21 action involves the initial control of benzodiazepines must be manufactured. substances with no legitimate medical distributed and stored in accordance use in the United States and must be with " 1301.71-1301.76 of Title 21 of the carried out in order to fulfill United Code of Federal Regulations. States international treaty obligations. 3. Labeling and Packaging All labels in any event. and labeling for commercial containers of each of the 21 benzodiazepines must In accordance with the provisions of comply with the requirements of 21 U.S.C. 811(d), this scheduling action is " 1302.03-1302.05 and 1302.06 of Title a formal rulemaking that is required by 21 of the Code of Federal Regulations by United States obligations under February 4, 1985. international convention. that 16. the 4. Inventory. Every registrant required Convention on Psychotropic Substances. to keep records who possesses any 1971. Such formal proceedings are quantity of any of the 21 conducted pursuant to the provisions of benzediazepines must lake inventories 5 U.S.C. 556 and 557, and as such. have pursuant to = 1304.11-1304.19 of Title been exempted from the consultation 21 of the Code of Federal Regulations, of requirements of Executive Order 12991 all stocks of these substances on hand. (46 FR 13193). 5. Records and Reports. All Dated: October 1. 1984. registrants required to keep records and submit reports pursuant to Part 1304 of Francis M. Mullen. fre Title 21 of the Code of Federal Administrator. Drug Enforcement Regulations shall do so regarding each Administration of the 21 benzodiazepines. a. Prescriptions. None of the 21 IFR Dec 04-28360 Filed 19-4-04: as am) benzodiatepines can be prescribed BILLING CODE 4410-00-18 98TH CONGRESS REPT. 98-835 2d Session HOUSE OF REPRESENTATIVES Part 1 DANGEROUS DRUG DIVERSION CONTROL ACT OF 1984 JUNE 12, 1984.-Ordered to be printed - Mr. HUGHES, from the Committee on the Judiciary, submitted the following REPORT [To accompany H.R. 5656 which on May 15, 1984, was referred jointly to the Committee on the Judiciary and the Committee on Energy and Commerce] [Including cost estimate of the Congressional Budget Office] The Committee on the Judiciary, to whom was referred the bill (H.R. 5656) to amend the Controlled Substances Act to strengthen the authority to prevent diversion of controlled substances, and for other purposes, having considered the same, report favorably there- on with an amendment and recommend that the bill as amended do pass. The amendment is as follows: Strike out all after the enacting clause and insert in lieu thereof the following: That (a) this Act may be cited as the "Dangerous Drug Diversion Control Act of 1984". (b) Whenever in sections 2 through 14 an amendment or repeal is expressed in terms of an amendment to, or repeal of, a section or other provision, the reference shall be considered to be made to a section or other provision of the Controlled Sub- stances Act, and whenever in sections 15 through 21 an amendment or repeal is ex- pressed in terms of an amendment to, or repeal of, a section or other provision, the reference shall be considered to be made to a section or other provision of the Con- trolled Substances Import and Export Act. SEC. 2. (a) Section 102 (21 U.S.C. 802) is amended by redesignating paragraphs (14) through (29) as paragraphs (15) through (30), respectively, and by adding after para- graph (13) the following: "(14) The term 'isomer' means the optical isomer, except as used in schedule I(c) and schedule II(a)(4). As used in schedule I(c), the term 'isomer' means the optical, positional, or geometric isomer. As used in schedule II(a)(4), the term 'isomer' means the optical or geometric isomer." (b) Paragraph (17) (as so redesignated) of section 102 is amended to read as fol- lows: "(17) The term 'narcotic drug' means any of the following whether produced di- rectly or indirectly by extraction from substances of vegetable origin, or independ- 31-006 o 10 The Subcommittee felt that these concerns were meritorious and narrowed the scope fo the factor to apply to "such other conduct which may threaten the public health and safety." This change sat- isfactorily responds to those concerns. Seizing drugs of an out-of-business registrant The American Pharmaceutical Association and the American Veterinary Medical Association expressed concern that a minimum 90-day period before the Attorney General could destroy the con- trolled substances sealed or seized from an out-of-business regis- trant provided for in H.R. 4698 was too short. The Subcommittee took these meritorious concerns into consideration in revising sec- tion 8 by lengthening the period of time and adding certain protec- tive procedures. Emergency scheduling The proposal for emergency scheduling was subject to extensive comment and concern by the American Medical Association, the American Pharmaceutical Association, the American Veterinary Medical Association and the Pharmaceutical Manufacturers Asso- ciation. All of these concerns were based on a perception that drugs currently used in medical treatment might be subject to temporary control by the Attorney General who would take into consideration principally law enforcement issues. Consequently, several witnesses urged that the bill permit emergency scheduling only if there were affirmative concurrence of the Secretary of Health and Human Services. Indeed, it appeared that the Administration had this un- derstanding of its proposal in view of the testimony of the Depart- ment of Health and Human Services. The Subcommittee believed that these concerns raised significant questions about the impact an emergency scheduling authority would have on the manufacture and distribution of drugs that are currently used in medical treatment. In examining the particular substances for which the scheduling action was most necessary, the Subcommittee concluded that limiting the authority only to sub- stances that have no currently accepted medical use in treatment addressed both the legitimate concerns of those in the health care industry and the principal danger to the public health. Registration of importers and exporters The original version to these amendments (H.R. 4698) included two sections (sections 19 and 21) that were designed to eliminate the cross-references from the Controlled Substances Import and Export Act (section 1008 (a) and (c)) (21 U.S.C. 958 (a) and (c)) to the Controlled Substances Act (section 303(a) and (d) (21 U.S.C. 823 (a) and (d)) with respect to the registration criteria for importers and exporters. At full Committee markup of the Subcommittee's reported bill, those sections were deleted because by eliminating language that related to the manufacture of drugs, they created the appearance of a change in policy although no policy change was intended. The current law is settled, and does not need to be revised to re- solve any ambiguity. The Administration and the affected parties 11 urged that the current law be retained. The Committee agreed and struck out those two sections. Hearing on application for registration to import Schedule I and II substances The Administration had urged that section 1008(h) (21 U.S.C. 958(h)) be amended to eliminate a right for registered bulk manu- facturers to intervene in the application of a party to become an importer of Schedule I or II substances. A recent proceeding under this section lasted for several years and involved a commitment of several thousand hours of DEA staff time. The Administration sug- gested that the hearing did not substantially contribute to the de- termination of the legal and factual issues involved. The Committee believes that the opportunity for public hearings in these matters are important and should be retained. The ques- tions of additional registration often involves economic questions concerning the adequacy of competitive conditions for which expert testimony can be valuable. Therefore, the Committee deleted that portion of section 22 of the Subcommittee's reported bill which would have eliminated the right to a public hearing. This action re- tains current law. The Committee, however, wants to express its concern that these hearings not be permitted to be used for purposes of unreasonable delay in the consideration of meritorious applications for registra- tion. The Committee urges that these matters be resolved expedi- tiously. SECTION-BY-SECTION ANALYSIS Section 1. Short Title: The Dangerous Drug Diversion Control Act of 1984. Section 2. (a) The term "isomer" is defined to eliminate the po- tential ambiguity regarding different types of isomers used in the definitions of various controlled substances. (b) ine term "marrin tring" in for added clarity with respect to the derivatives of opium and opiates and Newly the included derivatives in of coca leaves, including cocaine and ecgomme. the term are "poppy straw", and "concentrate of poppy straw", major narcotic raw materials that are imported into the United States. (c) Schedule II(A)(4) is amended to explicitly include as a deriva- tive of coca leaves cocaine and ecgonine and their salts, isomers, derivatives and salts of isomers and derivatives. Coupled with the definition of the term "isomer", as used in this paragraph of Sched- ule II. defenses to prosecutions under the Act with respect to co- caine will be precluded from raising what has been called the "isomer defense." Section 3. This section creates a new procedure for scheduling substances on an expedited and temporary basis which have no currently accepted medical use in treatment in the United States when they are found by the Attorney General to pose an imminent hazard to the public health. This new procedure is intended by the Committee to apply to what has been called "designer drugs", new chemical analogs or 12 variations of existing controlled substances, or other new sub- stances, which have a psychedelic, stimulant or depressant effect, and have a high potential for abuse. Examples of such drugs include PCE and PHP which have been clandestinely developed and manufactured to imitate the effects of the controlled psychedelic drug, PCP. Other substances, fentanyl analogs, have been developed and marketed illicitly as "synthetic heroin". In other cases, substances which have been known to chemists for some time, are "discovered" by illicit drug researchers to have psychedelic effects. The substance, MPPP, is an example, which is similar to the schedule II drug, meperidine (Demerol). In 1982, illicitly manufactured MPPP was sold in California. It was contaminated in the course of its improper manufacture with a re- lated toxic chemical, MPTP, which caused Parkinson's disease-like symptoms in the users. Over 140 cases of MPTP induced Parkin- son's Disease symptoms have been confirmed. The MPPP/MPTP incident appears to have been single incident. However, the ability to establish controls on MPPP, if its production for drug abuse were to be encountered more often, would be important to protect the public health and to prosecute those who wantonly risk the public health. Section 3 of the bill adds a new subsection (h) to the section re- lating to scheduling. Paragraph (1) provides that the Attorney General by order may schedule a substance in Schedule I without regard to the require- ment of 21 U.S.C 811(b) relating to the Secretary of Health and Human Services if the scheduling is necessary to avoid an immi- nent hazard to the public safety. The order may only be issued after 30 days have elapsed from the date of publication of a notice of intention to issue such a order in the Federal Register along with the grounds upon which such an order is to be issued. The order may only be issued after 30 days have elapsed from the date the Attorney General transmits notice of the proposed order to the Secretary of Health and Human Serv- ices. The two 30-days periods may be concurrent. Paragraph (2) provides that the scheduling shall expire at the end of 1 year from the issuance of the order. However, if a rule- making proceeding to schedule the substance has been initiated pursuant to section 201(a)(1) (21 U.S.C. 811(a)(1)), the Attorney Gen- eral may extend the temporary scheduling for up to 6 months. Paragraph (3) provides that the Attorney General in finding that a substance poses an imminent hazard to the public safety shall consider three factors in paragraphs (4), (5) and (6) of section 201(c): The substance's "history and current pattern of abuse"; "The scope, duration and significance of abuse"; "What, if any, risk there is to the public health"; and include in the consideration actual abuse, diversion from legitimate channels, and clandestine importation, manufacture, or distribution. Paragraph (4) provides that the Attorney General transmit to the Secretary of Health and Human Services notice of the order to schedule a substance that he proposes to issue. The Attorney Gen- eral is directed to take into consideration any comments submitted by the Secretary in response to the transmitted notice. The Attor- ney General's authority to issue a temporary scheduling order is List of Substances placed in "Temporary Scheduling to Avoid Imminent Hazards to Public Safety" Pursuant to 21 U.S.C. 811 (h) Methcathinone Sch : Aminorex Scn I Alpha-Ethyltryptamine Sch I 4-bromo-2,5-dimethoxyphenethylamine Sch I Thenylfentanyl Sch I Benzylfentanyl Sch I N,N-Dimethylamphetamine Sch I 4-Methylaminorex Sch I Beta-Hydroxy-3-methylfentanyl Sch I Acetyl-alpha-methylfentanyl Sch = Alpha-methylthiofentanyl Sch I Beta-hydroxyfentanyl Sch I 3-methylthiofentanyl Sch I Thiofentanyl Sch I 3,4-methylenedioxy-N-ethylamphetamine Sch I N-hydroxy-3,4-methylenedioxyampetamine Sch I Para-fluorofentanyl Sch I N-ethyl MDA Sch I N-hydroxy MDA Sch I 3,4-methylenedioxymethamphetamine Sch I 3-methylfentanyl Sch I 1-methyl-4-pheny1-4-propionoxypiperidine (MPPP) Sch I 1-(2-phenethyl)-4-pheny1-4-acetoxypiperidi (PEPAP) Sch - : Rohypnol Talking Points - Chemical name - flunitrazepam - The drug is a benzodiazepine, the same class as valium - The pill is 10 times strong than valium - The pill is round, flat, and the size of an antacid. The word "roche" (pronunced "RO- shay") with an encircled 2 are embosed on the tablet. - given as sleep aid or for the sedation of psychotics; in Latin American countries, it is used as a sediation for patients undergoing surgery - Slang terms - "roofies, "poor man's Quaalude, "ruffies", "roach", "forget pill", "Mexican valium", "Date rape drug" - Side effects - hallucinations - respiratory problems - sleep disturbances - anexity - amensia - reduces inhibitions - combined with alcohol, the pills have an added depressant effect - Some men have been known to give this drug to women in an alcoholic drink so he can sexually dominate her after the pill takes effect and she will not recall the incident - Dangerous pill since October, 1990 I Always classified as illegal in US - Produced in US by Roche, an American-Swiss pharmaceuticals company - Shipped to oversees markets - Usually re-enters US through traditional heorin and cocaine routes - Who uses the pill - teenagers - very cheap - price ranges from $.50 to $3 per pill - does not cause nausea or easily detectable in UAs - Kids get drunk quickly and it lasts longer - Easily available in all-night dance clubs, schools - gangs - used as part of initiation rites - used in gang rapings, which can also be part of an initiation rite - heroin addicts - enhances sedating effects of lower-purity heroin - cocaine addicts - use it ot parachute down from a binge - these two substances were found in grunge singer body, Curt Corbain, blood samples after a suicide attempt in Europe - Substance has caused two deaths in Texas - used primarily in the South January 10, 1996 Presidential Memorandum on the drug, Rohypnol Proposed Action President signs a Memorandum to the Attorney General to schedule Rohypnol as a Schedule I substance (subjecting it to the strongest possible restrictions under the law) under the Drug Abuse and Prevention Control Act. Purpose This drug is widely used by adolescents, the one age segment in which drug use is increasing. Senator Biden recently wrote a report on youth drug use, which addresses the use of this drug and he is proposing legislation to increase the restrictions on this drug. This Presidential Memorandum will show action and leadership -- that he is willing to address the growing youth drug use problem head-on, do all within his power to curb its use, and not wait for the legislative process to accomplish a goal that he can implement immediately. Background Rohypnol is a drug that has recently hit the youth scene and has quickly become popular. It was first documented in the U.S. in June 1993 by the National Institute on Drug Abuse. Its use incredibly pervasive in South Florida and its use by teenager has now been reported in 30 States. Rohypnol is classified as a depressant, and as such, it can be fatal if combined with alcohol. Although it is marketed legally in many countries around the world, it has no legal use in the United States. Where Rohypnol is available legally, it is primarily used as sedative/hypnotic to treat insomnia and for some anastethetic procedures. Rohypnol has been widely reported as used for date rape. In fact, in many areas and in a number of newspaper accounts, Rohypnol has been referred to as a "date rapte drug." The most famous example of Rohypnol overdose made the news when Kurt Cobain, lead singer of the rock band Nirvana, attempted suicide with a near fatal mixture of champagne and Rohypnol (Cobain was more successful the next time when he used a shotgun). Biden -- what does his bill actually say? What does changing to Schedule I really mean? Do we the authority to only do it temporarily? What are the steps that need to occur to schedule it "temporarily"? Who manufactures this drug and where? How many DEA busts have occurred in Florida and other States w/ regards to this drug? DRAFT ROHYPNOL - STATEMENT OF THE PROBLEM The abuse of Rohypnol (flunitrazepam), a Schedule IV controlled substance, was first documented in June 1993. At that time, Rohypnol was only seen in South Florida; since then, according to DEA reports, use of the drug has spread throughout the South and investigative cases have now been reported in 32 states and Puerto Rico. It is a drug that is often abused by our nation's youth and is often associated with date rape. Rohypnol has been described as 10 times as potent as diazepam (Valium) on a weight basis. Rohypnol slows psychomotor performance and induces amnesia, muscle relaxation and sleep. Its use may lead to the development of physical and psychic dependence. Rohypnol is marketed extensively worldwide but is not manufactured or available for medical use in the United States. DEA reports that Rohypnol is being publicized on the Internet with advice being given how to import into the U.S. The importation of Rohypnol as well as other prescription medication, is generally allowed regardless of citizenship or residency. The Code of Federal Regulations, 21 CFR 1311.27 allows an individual to import prescription drugs in his possession which he has lawfully obtained for his personal medical use or for administration to an animal accompanying him, providing the following conditions are met: (a) The controlled substance is in the original container in which it was dispensed to the individual; and (b) The individual makes a declaration to an appropriate official of the U.S. Customs Service stating: (1) That the controlled substance is possessed for his personal use, or for an animal accompanying him; and (2) The trade or chemical name and the symbol designating the schedule of the controlled substance if it appears on the container label, or, if such name does not appear on the label, the name and address of the pharmacy or practitioner who dispensed the substance and the prescription number, if any. U.S. Customs allows individuals to enter the drug at ports of entry when crossing into the U.S. when proper documentation, per 1311.27, is presented. FDA regulations permit individuals a 3 month supply for "personal use". DEA reports that many individuals are abusing this regulation by acquiring a three month supply daily in Mexico and then stock pile the drug in the United States. P.02/12 82:61 9661-22-833 DRAFT -2- The Rohypnol problem is further enhanced in that a traveller may properly declare at the port, but if later stopped in the U.S., the drugs may be seized by state authorities and the violator is subject to arrest. This is occurring in the State of Texas. For a prescription to be valid in the State of Texas it must have been issued by a doctor licensed and registered in Texas, or in another state if the doctor has a current Drug Enforcement Administration registration number and can legally prescribe controlled substances in that state. A prescription issued for a controlled substance by a doctor in Mexico is NOT VALID in Texas unless the doctor meets the above criteria. U.S. Customs does not enforce this state law. U.S. Customs has seized over the past quantities of the drug Rohypnol at U.S. Customs mail facilities. Regulations do not allow the mailing of the drug; it must accompany the individual when entering the United States. In South Florida, the drug is arriving primarily from Colombia via international mail services or commercial airlines with overnight mail appearing to be the preferred method of importation. Although the previous drug czar, Mr. Lee Brown, in December 1995, stated that this is a not a national problem, Federal, State and Local law enforcement agencies believe it is and that abuse of Rohypnol is likely to increase. CUSTOMS ACTION PLAN TO ADDRESS THE ROHYPNOL PROBLEM: OBJECTIVE: Prohibit or restrict entry of prescription drugs into the United States. In partnership with other law enforcement agencies and with local communities, decrease the number of crimes related to prescription drug abuse. SHORT TERM: A series of enforcement initiatives and enhancements designed to increase Customs enforcement efforts, thereby increasing the amounts of prescription drugs voluntarily surrendered to Customs and/or seized by local law enforcement agencies. Obtain or force compliance by the travelling public and thereby reduce the abuse problem. P.00/12 19:28 9661-22-833 DRAFT -3- 1) A letter from the President to Justice and Treasury is anticipated advising agencies of the level of abuse of the prescription drug Rohypnol. This letter most likely will advise that Treasury and Justice agencies should become proactive in addressing this problem. Customs should be proactive and write a letter (see attached) to DEA Administrator Constantine urging both agencies to work together to change regulations regarding the entry of prescription drugs into the United States. Tasking: Commissioner's office Start Date: February 22, 1996 2) Seek cooperation with FDA. Do FDA regulations override DEA regulations? Can they be easily changed? Tasking: Office of Field Operations, Office of Investigations Start Date: February 22, 1996 3) A letter should be written from U.S. Customs to Texas Department of Public Safety (DPS) advising DPS of Customs requirements to allow prescription drugs into the U.S, based on 21 USC 1311.27. This puts U.S. Customs on record with Texas DPS as recognizing the problem exists and what we can and will attempt to do about it. Tasking: Office of Investigations, Office of Field Operations Start Date: February 1996 4) Commissioner Weise should seek ONDCP support to recognize this as a national problem. Comment: In December 1995 was quoted as stating that this was not a national problem. Dr. Brown opposed - General McCaffrey may support Tasking: Commissioner's office Start Date: February 1996 2.00/12 19:29 9661-22-833 DRAFT -4- 6) Posting of flyers (see Del Rio example) Generic poster in English and Spanish on reverse side. This flyer would be posted at all POE's on the Southwest border and in Customs offices nationwide. Tasking: Office of Field Operations, Office of Investigations Start Date: February 1996 7) Media blitz per Port Director, Laredo suggestion. Work with local news stations, radio and newspapers along with other law enforcement agencies (ONDCP/State (s) /DEA/USC/FDA) to publicize increased efforts in enforcing the importation and unlawful distribution of prescription drugs Question: ONDCP Funding? Tasking: CMC (Public Affairs), Port Directors, Office of Investigations Start Date: February 1996 8) Seek cooperation with local law enforcement agencies in those states where it is against that State's law to bring prescription drugs into that state. Post a state law enforcement officer in Customs secondary. Question: Legal? For all prescriptions? Tasking: Office of Field Operations, Office of Investigations, Chief Counsel Start Date: February 1996 9) Initiate outreach efforts with local schools and the community. This would be a state/federal partnership. Tasking: Office of Investigations Start Date: March 1, 1996 P.00/12 19:29 9661-22-833 DRAFT -5- 10) Commissioner Weise to release a statement to the press regarding increased Customs efforts in partnership with other law enforcement agencies Tasking: Commissioner's office Start Date: March 1, 1996 11) Explore changes to Customs policy/authority to enforce state law. Can we enforce State law? Do we want to enforce State law? Can we use discretion? (Example: Allow for the Elderly/AIDS patient/Cancer, etc). Tasking: Office of Field Operations, Office of Investigations, Chief Counsel Start Date: March 1996 LONG TERM: Seek legislative change to the Controlled Substance Schedules for prescription drugs and/or in regulations regarding the importation of personal use quantities by residents/non- residents. Obtain compliance by the American public and thereby reduce the drug abuse problem nationally. Assist in a community policing effort to decrease crimes related to prescription drug abuse. 1) Support DEA's efforts to reschedule prescription drugs as a Schedule I drug. Comment: A change from Schedule IV to Schedule I is not likely to happen, however, DEA has stated they will begin this process. Tasking: Office of Investigations, Office of Field Operations DEA Start Date: February 13, 1996 - Continuing 219090'd 62:61 9661-22-833 DRAFT -6- 2) Seek Congressional support (Kiki De la Garza/Kasselbaum) for changes in law or regulations. Comment: Kasselbaum has asked for FDA reform. Tasking: Office of Congressional Affairs, Office of Field Operations, Office of Investigations, DEA and FDA Start Date: March 1, 1996 - continuing 3) Seek Change in 21 CFR 1311.27 and Customs regulations as follows: - Limit quantities to a 30 day supply per declaration, instead of the current 90 day allowance for controlled substances in general - Limit the exemption for entry of controlled substances for personal use to the standard "once in a 30 day" period which is currently 148.36). in effect for the $400 personal exemption (19 CFR - requirement for a 48 hour stay abroad to be eligible for the $400 personal exemption should be required for the exemption for entry of controlled substances for personal use, except in specifically defined cases (19 CFR 148.35 9a) ) - Require a written declaration for each entry of controlled substances for personal use (19CFR 148.13). - If not successful in placing prescription drugs in Schedule I, then seek a change in regulations allowing only non-residents to import prescription drugs for personal use. U.S. citizens would not be allowed to import for personal use unless a prescription can be obtained from a U.S. medical doctor. - In partnership with FDA enforce FDA labelling requirements in that if prescription drugs do not contain the following required information, entry will be denied: 21/20'd 19.29 9661-22-833 DRAFT -7- - description, indications of usage, contraindications, warnings, adverse, reactions, drug abuse and dependence, (if a controlled substance must so indicate), overdosage, dosage and administration. The physician's name and prescription number must appear on the container. Comment: Downside: AIDS/ELDERLY/Cancer/Financial considerations Enforceable? - Would involve seeking cooperation from other countries Tasking: Office of Field Operations, Office of Investigations in partnership with other agencies Start Date: February 22, 1996 - continuing 5) Through NAFTA negotiations, require Mexico to have their physicians log prescription dispensed and require identification to fill all prescriptions. Require that Mexican FDA police physicians and pharmacies to ensure that they are not allowing an individual to acquire more than a 3 month supply over a 3 month period. Comment: Realistic? NAFTA issues? Tasking: Office of Field Operations (NAFTA Task Force) Office of Investigations, Foreign Operations Start Date: March 1996 - continuing 6) Customs Attache to work closely with Mexican authorities to make known the prescription drug abuse problem in the United States and how Mexican authorities can work with the United States in stopping the problem Tasking: Customs Attache, Mexico Start Date: March 1996 - continuing 21/80'd FEB-22-1996 19:30 DRAFT -8- TEST Begin February 26, 1996 media blitz, posting of flyers, outreach and stationing of local law enforcement officers at ports of entry in the southwest border ports of Laredo, Del Rio, McAllen, Brownsville, El Paso. Evaluate after 90 days. Measure effectiveness Our effectiveness will be measured by: 1. The extent of cooperation by Mexican authorities 2. The extent of cooperation by U.S. law enforcement agencies, federal, state and local and Congressional members 3. The extent of cooperation with the local communities 4. Subsequent changes in monitoring dispensing of prescription drugs by Mexican authorities. 5. A change in the Controlled Substance Schedules, placing prescription drugs in Schedule I. REALISTIC? Not likely. 6. A change in regulations which would allow a 30 day supply of prescription drugs for non residents, NONE for U.S. residents unless a prescription can be obtained from a U.S. doctor. 7. A change in policy which would allow Customs to enforce state laws regarding prescription drugs 8. Changes in Customs policy - requiring a written CF 6059-B 9. Monitor seizure statistics and crime statistics. Is there a decrease in crime related to prescription drug abuse. Are seizures going down as the community is educated regarding abuse of the drug Rohypnol and other prescription drugs. 21/60'd FEB-22-1996 19:30 DEPARTMENT OF THE TREASURY THE U.S. CUSTOMS SERVICE DEL RIO. TEXAS NOTICE EVEN THOUGH A RETURNING UNITED STATES RESIDENT DECLARES MEDICATIONS CONTAINING CONTROLLED SUBSTANCES TO U. S. CUSTOMS AND CUSTOMS ALLOWS THE IMPORTATION. POSSESSION OF CERTAIN CONTROLLED SUBSTANCES IN THE STATE OF TEXAS MAY BE ILLEGAL. UNDER TEXAS LAW FOR A PRESCRIPTION CONTAINING CERTAIN CONTROLLED SUBSTANCES TO BE VALID IT MUST HAVE BEEN ISSUED BY A DOCTOR LICENSED AND REGISTERED IN TEXAS, OR IN ANOTHER STATE IF THE DOCTOR HAS A CURRENT DRUG ENFORCEMENT ADMINISTRATION NUMBER AND CAN LEGALLY PRESCRIBE CONTROLLED SUBSTANCES IN THAT STATE. A PRESCRIPTION ISSUED FOR A CONTROLLED SUBSTANCE BY A DOCTOR IN MEXICO IS NOT VALID IN TEXAS UNLESS THE DOCTOR MEETS THE ABOVE CRITERIA. QUESTIONS SHOULD BE DIRECTED TO A TEXAS DEPARTMENT OF PUBLIC SAFETY OFFICER. PORT DIRECTOR OF CUSTOMS DEL RIO, TEXAS 210) 703-2012 SEPLT TO PORT DIRECTOR -CE, BOX AM FEB-22-1996 19:30 21/01'd DRAFT The Honorable Thomas A. Constantine Administrator Drug Enforcement Administration Washington, D.C. 20537 Dear Mr. Constantine: The U.S. Customs Service and the Drug Enforcement Administration have each independently identified an issue which must be jointly addressed by our two agencies. Specifically, I am referring to the practice of importing, under the guise of for "personal use", small amounts of prescription medicines. Our respective agencies have identified the drug "Rohypnol" as one such drug, and others, which are being imported into the United States (U.S.) through our various ports of entry, most notably along the Southwest border. Rohypnol is not sold in the U.S., and has become a drug of abuse in Florida, Texas and in numerous other U.S. localities. I have been informed that a joint USC/DEA meeting was held on February 13, 1996 at your headquarters to discuss this problem. It appears the basis for allowing "personal use" quantities of prescription drugs into the U.S. is derived from Chapter 21 Code of Federal Regulations, Section 1311.27. This regulation, combined with Food and Drug Administration guidelines which define personal use as a 90 day supply, is enabling those individuals who are so inclined to abuse the system. To make matters worse, certain States, such as Texas, prohibit possession of prescribed drugs which do not conform to State regulations, which are legally imported through Customs under 21 CFR 1311.27. My staff is exploring alternatives within the Customs Regulations which would enable U.S. Customs to intercept these types of prescription drugs. However, unlike alcohol, there are no provisions to enforce state controls on other controlled substances. At this time, there does not appear to be any basis within the Customs Regulations to prevent abuses and importations utilizing this "loophole" in the Federal regulations. I am aware that it is no small undertaking, but it appears the only permanent solution to preventing abuses of prescription medicines is to rewrite 21 CFR 1311.27. P.11/12 02:00 9661-22-333 TOTAL P.12 It is refreshing to see that our two agencies continue to undertake joint strategies and initiatives to address common problems. ot Please call upon me if I or the Customs Service can be of assistance in helping you garner support for effecting the on necessary changes to the Federal Regulations. We must continue to closely coordinate this matter, as the Customs ou. Service must insure that any changes to 21 CFR 1311.27 are enforceable at our ports of entry. -us j h Sincerely, S in dE il George J. Weise Commissioner Me tc VE 'C' Pm 9 21 m P.12/12 19:31 9661-22-833 EXECUTIVE OFFICE OF THE PRESIDENT 22-Feb-1996 06:17pm TO: BURKE_D FROM: Mark Kleiman Crim. Just. 495 SUBJECT: Re: Conference Dennis: Rescheduling Rohypnol is probably only a partial solution. You might want to talk to Susan and get her thoughts. In any case, there's lots of prevention stuff to do, and methamphetamine is a much bigger problem, possibly a very big one indeed. In my previous I forgot to mention methcathinone, which is still a third problem. BOTEC could put together a pretty good emerging-drugs issues-and-options paper by conference time if we got going right away; one option would be to have CASA pay for it and BOTEC do it as a contractor for them. Aside from coerced-abstinence stuff (establishing coerced abstinence as a national policy, requiring states to make measurements and do plans as a condition of getting their crime and drugs money, creating legislation to make it a reality in federal probation and pretrial) I'm a little thin on legislative ideas. 1. Resources (people and research money) for ONDCP. This should be easy. 2 Restore some of the CSAT (treatment) demonstration-program money, some of the HUD drug-elimination money, some of the DoEd drug-free schools and communities money, with a requirement that ONDCP evaluate these programs and report to Congress in eighteen months about what's worth doing and what isn't. Argument: it's silly not to do something about these problems; if the money isn't currently being used right, let ONDCP sort it out. Maybe the Education money should be converted back from block grants, which have been abused, to categorical grants- in-aid, so Riley can make people spend it for the right stuff. But I think the HUD money has been well spent. 3 Authorize/require NIDA to conduct studies on drug trafficking, drug markets, and all aspects of drug abuse control including enforcement. Authorize/require CSAP to mount programs on preventing dealing as well as drug abuse. I know all of this is boring. I'll try to come up with something interesting. Mark