A Brief History of the FDA c Mark W. Mugler 1996 "It is seldom that liberty of any kind is lost all at once." (David Hume) "The road to Hell is paved with good intentions." (anonymous) The following brief history is adapted from U.S. Food and Drug Administration, Milestones in U.S. Food and Drug Law History, 1995, which can be found on the FDA web page. You should read it. The enthusiasm with which the authors trumpet the successive incursions of the FDA on the liberties of U.S. citizens is morbidly entertaining. This history focuses on FDA regulation of drugs, medical devices, food additives, and nutritional supplements. It minimizes coverage of FDA regulation of food (except as it affects regulation of food additives and nutritional supplements), cosmetics, animal drugs and feeds. It also minimizes coverage of regulation of pesticides, consumer products, and drug abuse, which are former FDA missions now assigned to other, equally unpalatable agencies. 1848 DRUG IMPORTATION ACT requires U.S. Customs inspection to stop entry of adulterated drugs from overseas. Note the strict construction of the Federal Government's involvement in interstate commerce. 1897 TEA IMPORTATION ACT provides for Customs inspection of all tea entering U.S. ports, at the expense of the importers. 1902 The BIOLOGICS CONTROL ACT is passed to insure purity and safety of serums, vaccines, and similar products used to prevent or treat diseases in humans. In 1970, regulation of biologics is transferred to the FDA. 1879-1906 U.S. Department of Agriculture investigates food adulteration and pushes for a national food and drug law. Former USDA officials organize lobbying efforts to secure a federal law against the misbranding and adulteration of foods and drugs. More than 100 food and drug bills are introduced in Congress. In 1902, Congress appropriates funds to establish food standards and to study the effects of chemicals on digestion and health. Shocking disclosures are made of the use of poisonous preservatives and dyes in foods and cure-all claims for worthless and dangerous patent medicines. An early example of the Iron Septagon at work. 1906 The original FOOD AND DRUGS ACT prohibits interstate commerce in misbranded and adulterated foods, drinks and drugs. The Department of Agriculture is authorized to seize unsafe substances and prosecute violators. Note that in the good old days, "misbranded" meant that the label did not accurately describe the contents, and "adulterated" meant that the claimed ingredients had been diluted, (as flour might be diluted by pea meal). The intent of the act was to provide penalties for consumer fraud and to prevent injury and death from poisons. 1911 In U.S. v. JOHNSON, the Supreme Court rules that the 1906 Food and Drugs Act did not prohibit false therapeutic claims but only false and misleading statements about the ingredients or identity of a drug. The decision is consistent with the intent of the act to prevent consumer fraud. 1912 In the first in a long, sorry history of plugging "loopholes" (one generation's compromise being the next generation's loophole), Congress enacts the SHERLEY AMENDMENT to overcome the ruling in U.S. v. Johnson. It prohibits labeling medicines with false therapeutic claims intended to defraud the purchaser, a standard difficult to prove, as shown in subsequent court cases. 1914 In U.S. v. LEXINGTON MILL AND ELEVATOR COMPANY, the Supreme Court rules that foods containing poisonous or deleterious ingredients are illegal when the quantity of such ingredients may be injurious. The decision is a compromise: it does not require proof of actual injury; on the other hand, the mere presence of such an ingredient is not sufficient to make a food illegal. 1924 In U.S. v. 95 BARRELS ALLEGED APPLE CIDER VINEGAR, the Supreme Court rules that the Food and Drugs Act condemns every statement, design or device which may mislead or deceive, even if technically true. This decision is notable because the Supreme Court, by legislating from the bench, begins to erode the Sherley Amendment principle of intent to defraud, a process continued in 1938 and thereafter. The decision is also notable for the government's use of seizure (asset forfeiture) as a tool to prevent allegedly unsafe products from entering interstate commerce (note that the defendant in the case is 95 barrels). The government was gripped with seizure fever 40 years before the War on Drugs. 1927-88 The Iron Septagon succeeds in creating a nexus for a petty regulatory dictatorship and in nurturing its growth over the years. A separate law enforcement agency is formed in 1927, first known as the Food, Drug, and Insecticide Administration and then, in 1930, as the Food and Drug Administration (FDA). FDA is transferred from the Department of Agriculture to the Federal Security Agency (later known as the Department of Health, Education and Welfare) in 1940, then to the Public Health Service, which in turn is incorporated, along with most of HEW, into the Department of Health and Human Services. In 1988, the FOOD AND DRUG ADMINISTRATION ACT officially establishes FDA as an agency of the Department of Health and Human Services with a Commissioner of Food and Drugs appointed by the President with the advice and consent of the Senate. 1933-38 The petty regulatory dictatorship rolls up its sleeves and gets to work. FDA recommends a complete revision of the "obsolete" 1906 Food and Drugs Act. A five-year legislative battle ensues. In 1937, an elixir of sulfanilamide contining a poisonous solvent kills 107 persons, mostly children, dramatizing the need to establish drug safety before marketing and to enact the pending food and drug law. 1938 THE FEDERAL FOOD, DRUG, AND COSMETIC (FDC) ACT replaces the 1906 act. It contains new provisions extending control to cosmetics and therapeutic devices; requiring new drugs to be shown safe before marketing--starting a new system of drug regulation; eliminating the pesky Sherley Amendment requirement that intent to defraud must be proved in drug misbranding cases; providing that safe tolerances be set for unavoidable poisonous substances; authorizing factory inspections; and adding the remedy of court injunctions to the previous penalties of seizures and prosecutions. 1939-40 FDA regulations create a class of drugs which may be dispensed only by prescription and only for stated uses. FDA hangs its hat on its mandate to stop "misbranding" (once intended to stop consumer fraud, as you may recall) and on act language stating that labels must state the uses for which drugs are recommended or prescribed. Ipso facto, by FDA logic, some drugs must be prescribed in the first place, and FDA must approve the stated uses! These regulations wrest the choice of drug therapies from the consumer and place it in the hands of the cartel. (After a 12-year struggle, the Alberty Food decision in 1950 and the Durham Humphrey amendment in 1951 will endorse and codify FDA's regulatory action). 1941 INSULIN AMENDMENT requires FDA to test and certify purity and potency of this life-saving drug for diabetes. 1943 In U.S. v. DOTTERWEICH, the Supreme Court rules that the responsible officials of a corporation, as well as the corporation itself, may be prosecuted for violations. It need not be proven that the officials intended, or even know of, the violations. This kind of decision, of course, casts a pall over innovation. 1944 PUBLIC HEALTH SERVICE ACT covers a broad spectrum of health concerns, including regulation of biological products and control of communicable diseases. 1945 PENICILLIN AMENDMENT requires FDA testing and certification of safety and effectiveness of all penicillin products. Later amendments extended this requirement to all antibiotics. (In 1983 such control was deauthorized as unnecessary, the Kefauver-Harris amendments of 1962 having required drug company testing and FDA approval prior to marketing.) 1948 MILLER AMENDMENT AFFIRMS that the Federal Food, Drug, and Cosmetic Act applies to goods that have moved in interstate commerce all the way to the ultimate consumer. Whereas consumer fraud and public safety could be carried only so far, the link to interstate commerce, an "elastic" clause in the Constitution if ever there was one, will prove most useful to the regulatory cartel in the years to come. 1950 In ALBERTY FOOD PRODUCTS CO. v. U.S., the court of appeals rules that the directions for use on a drug label must include the purpose for which the drug is offered. Therefore, a worthless remedy cannot escape the law by not stating the condition it is supposed to treat. This decision and the amendments of the following year provide FDA the basis for its current policies restricting "unapproved" or "off-label" uses of drugs, as well as the corollary policy of prohibiting health claims for non-drugs. (By FDA logic, non-drugs become "drugs" if a health claim is made for them and, if the provider has not run the regulatory gauntlet, the health claim thereupon becomes an unapproved use and the distribution of the "drug" is prohibited). See 1939-40. 1951 "DELANEY COMMITTEE" starts congressional investigation of the safety of chemicals in foods and cosmetics, laying the foundation for effective controls over pesticides, food additives, and colors. DURHAM-HUMPHREY AMENDMENT defines the kinds of drugs that cannot be safely used without medical supervision and restricts their sale to prescription by a licensed practitioner. See 1939-40, 1950. 1952 In U.S. v. CARDIFF, the Supreme Court rules that the factory inspection provision of the 1938 act is too vague to be enforced as criminal law (see factory inspection amendment, 1953). 1953 FACTORY INSPECTION AMENDMENT "clarifies" previous law and requires FDA to give manufacturers written reports of conditions observed during inspections and analyses of factory samples. Inspections now can be used as a hammer. Another "loophole" closed. 1958 FOOD ADDITIVES AMENDMENT enacted, requiring manufacturers of new food additives to establish safety. The Delaney proviso prohibits the approval of any food additive shown to induce cancer in humans or animals. 1959 U.S. CRANBERRY CROP recalled three weeks before Thanksgiving for FDA tests to ensure freedom from aminotriazole, a weedkiller found to cause cancer in laboratory animals. Recall that the FDA has both seizure and injunction power and considers itself a law enforcement agency as well as a regulatory agency. 1960 COLOR ADDITIVE AMENDMENTS enacted, requiring manufacturers to establish the safety of color additives in foods, drugs and cosmetics. 1962 THALIDOMIDE, a new sleeping pill, is found to have caused birth defects in thousands of babies born in western Europe. News reports on the role of Dr. Frances Kelsey, FDA medical officer, in keeping the drug off the U.S. market, arouse public support for stronger drug regulation. KEFAUVER-HARRIS DRUG AMENDMENTS PASSED to ensure greater drug safety. For the first time, drug manufacturers are required to prove to FDA the effectiveness of their products before marketing them. On might ask, how does the requirement to show effectiveness ensure greater drug safety? Why not beef up the safety protections? The answer is that the effectiveness provisions, by limiting market entry, enable FDA to exert more complete control over the smaller universe of drugs that can pass the effectiveness hurdle. The public got snookered again. Talk about consumer fraud! On the other hand, perhaps it is reassuring to think that the FDA has our interests at heart, denying us the use of medicines that might harm us so we won't have to sue the mean old drug companies should we in fact be harmed, and it's merely a coincidence that the mean old drug companies, in return for being shielded from lawsuits by FDA preemption, become completely beholden to FDA (and to the Congresspersons who oversee FDA's exercize of its powers) for their continued ability to sell their products. 1966 FDA CONTRACTS with the National Academy of Sciences/National Research Council to evaluate the effectiveness of 4,000 drugs approved on the basis of safety alone between 1938 and 1962. The motivation is clear: to build a case for retroactively applying Kefauver-Harris to already approved drugs, create media sensations, and press for laws "clarifying" Kefauver-Harris. FAIR PACKAGING AND LABELING ACT requires all consumer products in interstate commerce to be honestly and informatively labeled, with FDA enforcing provisions on foods, drugs, cosmetics, and medical devices. 1970 In UPJOHN v. FINCH the Court of Appeals upholds enforcement of the 1962 drug effectiveness amendments by ruling that commercial success alone does not constitute substantial evidence of drug safety and efficacy. 1972 OVER-THE-COUNTER DRUG review begun to enhance the safety, effectiveness and appropriate labeling of drugs sold without prescription. 1973 THE SUPREME COURT upholds the 1962 drug effectiveness law and endorses FDA action to control entire classes of products by regulations rather than to rely only on presumably more time-consuming litigation. EARLY 1970's Faulty intrauterine devices and cardiac pacemakers arouse public interest in better regulation of medical devices. See 1976. 1976 MEDICAL DEVICE AMENDMENTS passed to ensure safety and effectiveness of medical devices, including diagnostic products. The amendments require manufacturers to register with FDA and follow quality control procedures. Some products must have pre-market approval by FDA; others must meet performance standards before marketing. VITAMINS AND MINERALS (PROXMIRE) AMENDMENTS stop FDA from establishing standards limiting potency of vitamins and minerals in food supplements or regulating them as drugs based solely on potency. If you thought your vitamins and minerals are protected by the Proxmire amendments, you are wrong. If the manufacturer or distributor dares to make a therapeutic claim, FDA has been known to seize the offending substance as an unapproved drug. More later. 1983 ORPHAN DRUG ACT enables FDA to speed up and stremaline approval and marketing of drugs needed for treating rare diseases, which otherwise would not be profitable. The first of many amendments necessitated by FDA's hammerlock on market entry (see also 1984 and 1992). 1984 FINES ENHANCEMENT LAWS of 1984 and 1987 amend the U.S. Code to greatly increase penalties for all federal offenses. The maximum fine for individuals is now $100,000 for each offense and $250,000 if the violation is a felony or causes death. For corporations, the amounts are doubled. Thank you, Uncle Sam, I feel safer now. DRUG PRICE COMPETITION AND PATENT TERM RESTORATION ACT expedites the availability of less costly generic drugs by permitting FDA to approve applications to market generic versions of brand-name drugs without repeating the research done to prove them safe and effective. At the same time, the brand-name companies can apply for up to five years longer patent protection for the new medicines they developed to make up for time lost while their products were going through FDA's approval process. 1985 AIDS TEST FOR BLOOD approved by FDA in its first major action to protect patients from infected donors. 1986 CHILDHOOD VACCINE ACT requires patient information on vaccines, gives FDA authority to recall biologics, and authorizes civil penalties. 1987 THE PRESCRIPTION DRUG MARKETING ACT bans the diversion of prescription drugs from legitimate commercial channels. Congress finds that the resale of such drugs leads to the distribution of mislabeled, adulterated, subpotent, or counterfeit drugs to the public. The new law requires drug wholesalers to be licensed by the states; restricts reimportation from other countries; and bans sale, trade or purchase of drug samples, and traffic or counterfeiting of redeemable drug coupons. LATE 1980's Fractures of the Bjork-Shiley convexo-concave heart valve are reported. See 1990. 1990 NUTRITION LABELING AND EDUCATION ACT requires all packaged foods to bear nutrition labeling and all health claims for foods to be consistent with terms defined by the Secretary of Health and Human Services. The law preempts state requirements as to food standards, nutrition labeling, and health claims. SAFE MEDICAL DEVICES ACT requires medical device user facilities such as hospitals and nursing homes to report promptly to FDA incidents that reasonably suggest a probability that a medical device caused or contributed to the death, serious illness, or serious injury of a patient. The act requires manufacturers to conduct post-market surveillance on devices that are permanent implants and whose failure may cause serious health consequences or death, and to establish methods for tracing and locating patients depending on such devices. The act authorizes FDA to order device product recalls, to issue "stop use" notices to health professionals and user facilities, and to impose civil penalties (fines) after administrative hearings. EARLY 1990's Reports of leaking silicone gel breast implants prompt FDA to undertake a hyperagressive enforcement campaign. 1992 GENERIC DRUG ENFORCEMENT ACT imposes debarment and other penalties for illegal acts involving approval of abbreviated drug applications. PRESCRIPTION DRUG USER FEE ACT requires drug and biologics manufacturers to pay fees for drug and biologics applications and supplements. In addition, these firms must pay an annual establishment fee and annual product fees. FDA will use these funds to hire more reviewers to assess applications. Drug companies suppported this extortion, figuring they would lose less in fees than in foregone profits from FDA stonewalling and delay. 1994 DIETARY SUPPLEMENT HEALTH AND EDUCATION ACT establishes specific labeling requirements, provides a regulatory framework, and authorizes FDA to promulgate good manufacturing practice regulations for "dietary supplements" and "dietary ingredients" and classifies them as food. The act also establishes a commission to recommend how to regulate label claims. 1996 Facing House and Senate committee bills that would force it to streamline its procedures for drug and device approval, the FDA employs a classic political divide and conquer strategy: it approves streamlined procedures only for AIDS drugs, cancer drugs, and certain medical devices, thereby appeasing key interest groups and undercutting efforts to achieve broader reform.