By John P. Swann, Ph.D.
FDA History Office
(from George Kurian, ed., The Historical Guide to American Government (New York: Oxford University Press, 1998))
The U S. Food and Drug Administration is a scientific, regulatory, and public health agency that oversees items accounting for 25 cents of every dollar spent by consumers. Its jurisdiction encompasses most food products (other than meat and poultry), human and animal drugs, therapeutic agents of biological origin, medical devices, radiation-emitting products for consumer, medical, and occupational use, cosmetics, and animal feed. The agency grew from a single chemist in the U.S. Department of Agriculture in 1862 to a staff of approximately 9,100 employees and a budget of $1.294 billion in 2001, comprising chemists, pharmacologists, physicians, microbiologists, veterinarians, pharmacists, lawyers, and many others. About one-third of the agency's employees are stationed outside of the Washington, D. C. area, staffing over 150 field offices and laboratories, including five regional offices and 20 district offices. Agency scientists evaluate applications for new human drugs and biologics, complex medical devices, food and color additives, infant formulas, and animal drugs. Also, the FDA monitors the manufacture, import, transport, storage, and sale of about $1 trillion worth of products annually at a cost to taxpayers of about $3 per person. Investigators and inspectors visit more than 16,000 facilities a year, and arrange with state governments to help increase the number of facilities checked.
Beginning as the Division of Chemistry and then (after July 1901) the Bureau of Chemistry, the modern era of the FDA dates to 1906 with the passage of the Federal Food and Drugs Act; this added regulatory functions to the agency's scientific mission. The Bureau of Chemistry's name changed to the Food, Drug, and Insecticide Administration in July 1927, when the nonregulatory research functions of the bureau were transferred elsewhere in the department. In July 1930 the name was shortened to the present version. FDA remained under the Department of Agriculture until June 1940, when the agency was moved to the new Federal Security Agency. In April 1953 the agency again was transferred, to the Department of Health, Education, and Welfare (HEW). Fifteen years later FDA became part of the Public Health Service within HEW, and in May 1980 the education function was removed from HEW to create the Department of Health and Human Services, FDA's current home. To understand the development of this agency is to understand the laws it regulates, how the FDA has administered these laws, how the courts have interpreted the legislation, and how major events have driven all three.
States exercised the principal control over domestically produced and distributed foods and drugs in the 19th century, control that was markedly inconsistent from state to state. Federal authority was limited mostly to imported foods and drugs. Adulteration and misbranding of foods and drugs had long been a fixture in the American cultural landscape, though the egregiousness of the problems seemed to have increased by the late 19th century (or at least they became more identifiable). By this time science had advanced significantly in its ability to detect this sort of fraud. Also, legitimate manufacturers were becoming more concerned that their trade would be undermined by purveyors of deceitful goods. Quinine-containing cinchona bark powder could be made less therapeutically effective--and much more profitable--by cutting it with just about anything, alum and clay masked poor wheat flour and thus netted a heftier return for the unethical company, and sufferers of any number of serious or self-limited diseases were relieved only of their finances by vendors of worthless nostrums. Even the so-called ethical drug firms were guilty of this practice.
The Division of Chemistry began investigating the adulteration of agricultural commodities as early as 1867. When Harvey Washington Wiley arrived as chief chemist in 1883, the government's handling of the adulteration and misbranding of food and drugs took a decidedly different course, which eventually helped spur public indignation at the problem. Wiley expanded the division's research in this area, exemplified by Foods and Food Adulterants, a ten-part study published from 1887 to 1902. He demonstrated his concern about chemical preservatives as adulterants in the highly publicized "poison squad" experiments, in which able-bodied volunteers consumed varying amounts of questionable food additives to determine their impact on health. And Wiley unified a variety of groups behind a federal law to prohibit the adulteration and misbranding of food and drugs, including state chemists and food and drug inspectors, the General Federation of Women's Clubs, and national associations of physicians and pharmacists.
While Wiley was stumping for a law, muckraking journalists such as Samuel Hopkins Adams exposed in vivid detail the hazards of the marketplace. In fact, the nauseating condition of the meat-packing industry that Upton Sinclair captured in The Jungle was the final precipitating force behind both a meat inspection law and a comprehensive food and drug law. Since 1879 nearly 100 bills had been introduced in Congress to regulate food and drugs; on 30 June 1906 President Roosevelt signed the Food and Drugs Act, known simply as the Wiley Act, a pillar of the Progressive era.
This act, which the Bureau of Chemistry was charged to administer, prohibited the interstate transport of unlawful food and drugs under penalty of seizure of the questionable products and/or prosecution of the responsible parties. The basis of the law rested on the regulation of product labeling rather than pre-market approval. Drugs, defined in accordance with the standards of strength, quality, and purity in the United States Pharmacopoeia and the National Formulary, could not be sold in any other condition unless the specific variations from the applicable standards were plainly stated on the label. Foods were not defined according to analogous standards, but the law prohibited the addition of any ingredients that would substitute for the food, conceal damage, pose a health hazard, or constitute a filthy or decomposed substance. Interpretations of the food provisions in the law led to many, sometimes protracted, court battles. If the manufacturer opted to list the weight or measure of a food, this had to be done accurately. Also, the food or drug label could not be false or misleading in any particular, and the presence and amount of eleven dangerous ingredients, including alcohol, heroin, and cocaine, had to be listed. The bureau's regulatory emphasis under Wiley centered on foods, which he believed posed a greater public health problem than adulterated or misbranded drugs. Wiley generally held a dim view of chemical additives to foods, championing an approach that considered most to be unnecessary adulterants. On this he clashed often with Secretary of Agriculture James Wilson, and on occasion President Roosevelt himself had to decide government policy on food regulation. Wiley's personal administrative authority under the act was diluted early on when Wilson created a Board of Food and Drug Inspection in 1907 to establish agency policy in enforcing the law. Similarly, the creation of the Referee Board of Consulting Scientific Experts in the following year to advise the department on safety issues associated with food additives undercut Wiley's scientific authority. The bureau had been developing informal standards for many foods in collaboration with outside experts since 1903, an activity that continued after the 1906 act. However, courts differed on the role these informal standards could play in cases. Separate laws established standards for some specific foods, such as apples and butter, as well as for canned foods.
After Wiley's resignation in 1912, the bureau devoted more effort to drug regulation, with some emphasis on the so-called patent medicines. While the law was much clearer about drug standards than standards for foods, misbranding was the source of considerable controversy in the regulation of drugs. A year earlier the Supreme Court ruled that the law did not--contrary to the government's interpretation--apply to false therapeutic claims. An amendment in the year of Wiley's resignation attempted to correct the language of the law. But it put the bureau in the difficult position of attempting to prove in court that manufacturers of drugs labeled with false therapeutic claims intended to defraud consumers. The bureau lost several cases against egregious products, but seizures of misbranded and adulterated drugs nevertheless increased in the 1920s and 1930s.
With the election of Franklin Roosevelt and the death in 1930 of the embodiment of the 1906 act--Wiley--the FDA now had a receptive ear to petition for needed changes in the law: legally mandated quality and identity standards for foods, prohibition of false therapeutic claims for drugs, coverage of cosmetics and medical devices, clarification of the FDA's right to conduct factory inspections, and control of product advertising, among other items. A new generation of muckraking journalists and consumer protection organizations aided in pushing a reluctant Congress to sponsor a bill to replace the old law. The FDA itself exemplified the state of affairs in the marketplace by assembling a collection of products that illustrated shortcomings in the 1906 law. It included Banbar, a worthless "cure" for diabetes that the old law protected; Lash-Lure, an eyelash dye that blinded many women; numerous examples of foods deceptively packaged or labeled; Radithor, a radium-containing tonic that sentenced users to a slow and painful death; and the Wilhide Exhaler, which falsely promised to cure tuberculosis and other pulmonary diseases. A reporter dubbed this exhibit "The American Chamber of Horrors," a title not far from the truth since all the products exhibited were legal under the existing law.
Languishing in Congress for five years, the bill that would replace the 1906 was ultimately enhanced and passed in the wake of a therapeutic disaster in 1937. A Tennessee drug company marketed a form of the new sulfa wonder drug that would appeal to pediatric patients, Elixir Sulfanilamide. However, the solvent in this untested product was a highly toxic chemical analogue of antifreeze; over 100 people died, many of whom were children. The public outcry not only reshaped the drug provisions of the new law to prevent such an event from happening again, it propelled the bill itself through Congress. FDR signed the Food, Drug, and Cosmetic Act on 25 June 1938.
The new law brought cosmetics and medical devices under control, and it required that drugs be labeled with adequate directions for safe use. Moreover, it mandated pre-market approval of all new drugs, such that a manufacturer would have to prove to FDA that a drug were safe before it could be sold. It irrefutably prohibited false therapeutic claims for drugs, although a separate law granted the Federal Trade Commission jurisdiction over drug advertising. The act also corrected abuses in food packaging and quality, and it mandated legally enforceable food standards. Tolerances for certain poisonous substances were addressed. The law formally authorized factory inspections, and it added injunctions to the enforcement tools at the agency's disposal.
Enforcement of the new law came swiftly. Within two months of the passage of the act, the FDA began to identify drugs such as the sulfas that simply could not be labeled for safe use directly by the patient--they would require a prescription from a physician. The ensuing debate by the FDA, industry, and health practitioners over what constituted a prescription and an over-the-counter drug was resolved in the Durham-Humphrey Amendment of 1951. From the 1940s to the 1960s, the abuse of amphetamines and barbiturates required more regulatory effort by FDA than all other drug problems combined. Furthermore, the new law ushered in a flood of new drugs applications, over 6,000 in the first nine years, and 13,000 by 1962.
A new drug law in that year, the Kefauver-Harris Amendments, derived in large part from hearings held by Senator Estes Kefauver. As with the 1938 act, a therapeutic disaster compelled passage of the new law; in this case the disaster was narrowly averted. Thalidomide, a sedative that was never approved in this country, produced thousands of grossly deformed newborns outside of the United States. The new law mandated efficacy as well as safety before a drug could be marketed, required FDA to assess the efficacy of all drugs introduced since 1938, instituted stricter agency control over drug trials (including a requirement that patients involved must give their informed consent), transferred from the Federal Trade Commission to the FDA regulation of prescription drug advertising, established good manufacturing practices by the drug industry, and granted the FDA greater powers to access company production and control records to verify those practices. Three years later Congress gave the FDA enhanced control over amphetamines, barbiturates, hallucinogens, and other drugs of considerable abuse potential in the Drug Abuse Control Amendments of 1965. That function was consolidated with similar responsibilities in 1968 under an organization that gave rise to the Drug Enforcement Administration.
The first food standards to be issued under the 1938 act were for canned tomato products; by the 1960s about half of the food supply was subject to a standard. As food technology changed and the number of possible ingredients--including fortifying nutrients--grew, the agency developed recipe standards for foods, lists of ingredients that could lawfully be included in a product. A food that varied from the recipe would have to be labeled an imitation. Following hearings in the early 1950s under Representative James Delaney, a series of laws addressing pesticide residues (1954), food additives (1958), and color additives (1960) gave the FDA much tighter control over the growing list of chemicals entering the food supply, putting the onus on manufacturers to establish their safety. While tolerances could be established for many chemicals, a provision of the 1958 law, the Delaney Clause, banned any carcinogenic additive.
FDA pursued numerous cases of food misbranding in the 1950s and 1960s, most deriving from false nutritional claims and unscientific enrichment, with mixed success in the courts. In 1973, following hearings the agency convened to address the vitamin fortification of foods and the claims made for dietary supplements, the FDA issued regulations for special dietary foods, including vitamins and minerals. The public response to these regulations helped lead Congress in 1976 to prohibit the FDA from controlling the potency of dietary supplements, although the agency maintained authority to regulate enriched foods.
Cosmetics and medical devices, which the Post Office Department and the Federal Trade Commission had overseen to a limited extent prior to 1938, came under FDA authority as well after 1938. While pre-market approval did not apply to devices, in every other sense the new law equated them to drugs for regulatory purposes. As the FDA had to deal with both increasing medical device quackery and a proliferation of medical technology in the post-World War II years, Congress considered a comparable device law when it passed the 1962 drug amendments. The legislation having failed to develop, the Secretary of HEW commissioned the Study Group on Medical Devices, which recommended in 1970 that medical devices be classified according to their comparative risk, and regulated accordingly. The 1976 Medical Device Amendments, coming on the heels of a therapeutic disaster in which thousands of women were injured by the Dalkon Shield intrauterine device, provided for three classes of medical devices, each requiring a different level of regulatory scrutiny--up to pre-market approval.
The 1938 act required colors to be certified as harmless and suitable by the FDA for their use in cosmetics. The 1960 color amendments strengthened the safety requirement for color additives, necessitating additional testing for many existing cosmetics to meet the new safety standard. The FDA attempted to interpret the new law as applying to every ingredient of color-imparting products, such as lipstick and rouge, but the courts rebuffed this proposal.
Another agency responsibility, veterinary medicine, had been stipulated since the 1906 act; foods included animal feed, and drugs included veterinary pharmaceuticals. Likewise, animal drugs were included in the provisions for new drugs under the 1938 law and the 1962 drug amendments. However, the Food Additives Amendment of 1958 had an impact too, since drugs used in animal feed were also considered additives--and thus subject to the provisions of the food additive petition process. The Delaney Clause prohibiting carcinogenic food additives was modified by the DES proviso in 1962, named for diethylstilbestrol, a hormone used against miscarriages in humans and to promote growth in food-producing animals. The proviso permitted the use of possible carcinogens in such animals as long as residues of the product did not remain in edible tissues. The Animal Drug Amendments of 1968 combined veterinary drugs and additives into a unified approval process under the authority of the Bureau of Animal Drugs in the FDA.
In the late 1960s and 1970s the FDA lost some of its responsibilities but acquired many more. Shortly after the FDA became a part of the Public Health Service, the Department of Health, Education, and Welfare transferred several functions administered by other PHS agencies to the FDA, including regulation of food on planes and other interstate travel carriers, control over unnecessary radiation from consumer and professional electronic products, and pre-market licensing authority for therapeutic agents of biological origin. The latter originated under the predecessor of the National Institutes of Health in the Biologics Control Act of 1902, which followed the deaths of thirteen children from a tetanus-tainted batch of diphtheria antitoxin in St. Louis, and nine pediatric fatalities from similar circumstances in Camden, New Jersey. Congress had authorized the FDA to regulate consumer products such as potential poisons, hazardous toys, and flammable fabrics in a number of laws dating back to 1927, but this function was transferred to the Consumer Product Safety Commission in 1973.
Changes in the work of the FDA have come rapidly in the past 20 years, shaped at least in part by political pressure, consumer activism, and industry involvement. Patient advocacy groups influenced a law to stimulate industry interest in developing so-called orphan drugs for rare diseases, and they played a role in the agency's development of accelerated techniques for drug approval, beginning with drugs for AIDS. Congress passed a law that simultaneously extended patent terms to account for time consumed by the drug approval process and facilitated the approval of generic human and animal drugs to offer a lower-cost alternative to brand name pharmaceuticals. Also, Congress instituted procedures for industry to reimburse the FDA for review of drugs and biologics to speed the agency's evaluations.
Other laws have mandated reporting of adverse reactions to medical devices, post-market monitoring of implants and other devices that pose a serious health risk, recall authority for the FDA over medical devices, and certification and annual inspection of mammography facilities. Among food regulatory issues in the past two decades, Congress issued a singular prohibition against the FDA's banning saccharin under the Delaney Clause on the grounds that the sweetener had been shown to cause cancer in laboratory animals; instead, saccharin would have to carry a label warning. In 1990 Congress passed the Nutrition Labeling and Education Act, which completely reformulated the way food products convey basic nutritional information. Four years later, after intense lobbying by the dietary supplement industry, Congress permitted supplements to carry substantiated statements about the role of such products in health, provided they issued a disclaimer that FDA had not evaluated the statements. Moreover, the FDA rather than industry had the burden of proving that a dietary supplement was misbranded or adulterated.
The burgeoning interest in reinventing government and regulatory reform in the 1990s very much included the FDA, with the greatest interest focusing on the agency's time spent in evaluating therapeutic and other products. These were by no means original developments, at least as far as FDA was concerned. Numerous Congressional investigations, external and internal committee reports, independent fact-finding missions, and other venues of inquiry have studied the agency's mission and needs through much of the past century: precisely what one would expect for one of the oldest consumer regulatory agencies in the government, with such a broad responsibility for the public health, sometimes covering issues that have polarized large segments of American society. Such issued included sodium benzoate, sulfur dioxide, and other food preservatives during the Wiley era; Banbar in the 1930s; aminotriazole-tainted cranberries in the 1950s; vitamins in the 1970s; and breast implants in the 1990s. But these and other high visibility cases were just a small fraction of the agency's work, arcane to most of the public, but nevertheless a key ingredient in 20th century U.S. history.
Selected Additional Readings: www.fda.gov/opacom/morechoices/sources.html
Information from the Food and Drug Administration