FDA Overview

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FDA Overview

Introduction: History of Food and Drug Regulation

The Food and Drug Administration (FDA), established in 1930 as a part of the US Department of Health and Human Services (HHS), regulates products accounting for roughly 25% of the United States gross national product.

You may not realize the number of products you use in a given day that are regulated by the FDA. The label on the juice you drink for breakfast, the cosmetics you apply before work, the array of dietary supplements you take before dashing out the door, the food you feed your pets, the aspirin you take after a long day, and the contact lenses you place on your eyes are all regulated by this Rockville, Maryland-based agency. Because of the FDA, Americans largely can take for granted that these products are safe.

By examining the history of food and drug regulation, you can get a sense of the breadth of the agency’s mission and the forces that have led to the agency’s present size and role as one of the world’s most respected public health agencies. (An extensive bibliography included at the end of this article provides detailed references.)

Until the 20th century, drugs were regulated primarily by state and local governments. Drugs "could be bought and sold like any other consumer good" (US Regulatory Affairs History, Chapter 1). Regulation became more stringent as medical technology improved and high-profile incidents highlighted the need for at least some degree of government monitoring of these products.

Virus-Toxin Law of 1902: One of the first such incidents was associated with a vaccine. After patients suffered injuries from diphtheria vaccine "contaminated with tetanus," Congress passed the Virus-Toxin law (also referred to as the Biologics Control Act), that required licensing of biologics establishments, inspections of vaccine manufacturers, and premarket approval of vaccines and other products (Hyman, 1998; CBER, Commemorating, 2002; CBER, CBER Vision, 2002). This law also is referred to as the Biologics Control Act.
Food and Drug Act of 1906: As the new century began, widely publicized reports began to highlight severe problems in our country’s food and drug industry. One of the most dramatic of these reports was Upton Sinclair’s book, The Jungle, which graphically illustrated problems in the nation’s meat processing industry. Samuel Hopkins Adams’ magazine articles concerning what he called the Great American Fraud sparked similar concerns about fraudulent patent medicines containing dangerous ingredients such as alcohol, cocaine, morphine, and opium advertised by their makers as cures for diseases such as cancer and tuberculosis. These and other reports, along with extensive lobbying by Dr. Harvey Wiley, then director of the USDA’s Bureau of Chemistry, the eventual precursor to the FDA, spurred Congress to pass and President Theodore Roosevelt to sign the 1906 Food and Drug Act.
The 1906 Act prohibited the marketing of adulterated (meaning, contaminated) and misbranded food and drugs. Under the Act, such products were subject to seizure by the government. However, the law did not limit the claims a manufacturer can make with respect to their product as long as the product was correctly identified. The Act also did not require premarket inspections and approval.
Federal Food, Drug and Cosmetic Act [FD&C Act] of 1938: In 1937, nearly 100 people died after ingesting a product called Elixir Sulfanilamide, which was prepared using a chemical called diethylene glycol.
- Although the manufacturer technically violated the 1906 Act because the product was called an elixir (by definition this is supposed to contain alcohol, and this product did not), the company’s failure to test the product for safety and to label the product adequately were not violations of the law.
- The 1938 Act was passed to ensure that such a tragedy would not occur again. Among other things, the 1938 Act did the following: compelled manufacturers to demonstrate to the FDA the safety of new drugs prior to marketing; allowed the FDA to inspect manufacturing facilities; set tolerances for certain substances such as pesticides; extended FDA regulation to color additives and cosmetics; allowed the FDA to seek injunctions from courts; and provided detailed legal definitions of drug, devices, cosmetics, and labeling (US Regulatory Affairs History, Chapter 1; Hyman, 1998; Janssen, 1981). For instance, a drug is defined under section 201(g) of the Act as "articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals" and "articles (other than food) intended to affect the structure or any function of the body of man or other animals."
Durham-Humphrey Amendment of 1951: In 1951, the Act was amended to formally distinguish between prescription and over-the-counter drugs. Until that time, all drugs could be purchased over-the-counter by consumers. Prescription drugs were required to contain a warning that the drugs could be dispensed legally only with the authorization of a health professional.
Food Additive Amendment of 1958 and Color Additive Amendments of 1960: These amendments required premarket approval by the FDA of food components and color additives not "generally recognized as safe" by the scientific community. A food additive is defined in section 201(s) of the Federal Food, Drug and Cosmetic Act as "any substance the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting any food" unless it is generally recognized as safe based on scientific studies or historical use of the substance in foods. Manufacturers submit petitions to the agency with safety information about the additive, and, if approved, the FDA publishes a regulation in the Federal Register "specifying conditions of use" for the product (FDA Almanac: Center for Food Safety and Applied Nutrition, 1997). In 1960, a similar law was passed regarding color additives in foods, drugs, and cosmetics. Color additives are defined in section 201(t) as dyes or pigments that are "capable (alone or through reaction with other substances) of imparting color" to a food, drug, cosmetic, or part of the human body which the product affects or is applied to.
- The use of additives that are shown to be carcinogenic (cancer-causing) in animals or humans is prohibited under the Delaney Clause, a provision of both the Food Additives Amendment of 1958 and the Color Additives Amendments of 1960.
- The Food Quality Protection Act of 1996 exempted pesticide residues from the Delaney Clause but requires that there be reasonable certainty of no harm to consumers for pesticide residues in raw and processed foods.
Kefauver-Harris Amendment of 1962: Reports of birth defects in European nations caused by thalidomide, a drug about to be introduced into the United States, highlighted the need for more FDA regulation. Among other things, the amendment requires drug manufacturers to show the effectiveness of their products as well as their safety, to report adverse events to the FDA, and to ensure that their advertisements to physicians disclose the risks as well as the benefits of their products. Informed consent was required from participants in clinical studies. The FDA also was given jurisdiction over prescription drug advertising. In addition, the agency was required to approve a regulatory submission known as a new drug application before a company could market a new drug and be allowed to issue good manufacturing practice guidelines governing how drugs were to be manufactured. Inspection of drug manufacturers was mandated every 2 years.
Medical Device Amendments of 1976: The Amendments clarified the definition of device and categorized medical devices based on risk. Medical devices were required to meet certain performance standards and mandates recordkeeping and adverse event reporting. The amendments revised the definition of medical device as defined in section 201(h) of the Act and defined a device as "an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar related article, which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purpose."
Anti-Tampering Regulations: In 1982, 7 people died after Tylenol capsules were contaminated with cyanide. Tylenol maker Johnson & Johnson recalled $100 million worth of the product and introduced "tamper-resistant" packaging. After similar incidents in 1986, the company replaced capsules with caplets, which were harder to contaminate. FDA anti-tampering regulations require that "cosmetic liquid oral hygiene products" and vaginal products, contact lens solutions, and most over-the-counter drugs to be packaged in tamper-resistant packages. Products’ packaging must be "distinctive by design," and the package labeling must indicate to consumers what tamper-resistant measures are being used. The Federal Anti-Tampering Act makes tampering with consumer products a felony punishable by up to 10 years in jail.
Tamper-resistant packaging is defined as a package that has "an indicator or barrier to entry, which, if breached or missing, can reasonably be expected to provide visible evidence to consumers that tampering has occurred." According to the FDA, blister packs (tablets or capsules "individually sealed in clear plastic or plastic compartments with foil or paper backing"), film wrappers ("transparent film - wrapped securely around the entire product container"), aerosol containers ("believed to be inherently tamper-resistant because of their design"); tape seals; break-away caps, and foil paper or plastic pouches that "must be torn or broken to obtain the product" are examples of anti-tampering measures.
Orphan Drug Act of 1983: Drugs intended for the treatment of "rare diseases and conditions" may be designated orphan drugs under the 1983 Orphan Drug Act, which was intended to help promote research on rare diseases, substance abuse treatments, or products intended to treat diseases in third-world nations (U.S. Regulatory Affairs History, Fundamentals of Regulatory Affairs, Chap. 1; Chap. 16, Orphan Products, p. 127). "Rare" diseases were defined as diseases affecting fewer than 200,000 people or diseases that affect more than 200,000 people but where circumstances are such that a company is unlikely to recoup its costs. Under FDA regulations, the law applies to medical devices as well as drugs. Device manufacturers can request a humanitarian use device designation for devices intended to treat conditions in fewer than 4,000 people where alternatives are unavailable.
- By providing both tax credits to help defray half of the cost of clinical research and 7 years of marketing exclusivity to a drug manufacturer (in addition to the time granted under patents held by the company) for the treatment of the rare disorder once a product is approved, the law provides manufacturers with incentives to develop products for diseases and conditions in circumstances where the company otherwise might be unable to recoup its investment in researching, developing, and marketing a product for such a small number of patients.
- The FDA’s Office of Orphan Products Development administers this program, works with FDA Centers that review these products, and provides research grants to fund clinical studies on orphan products.
- According to the Office’s Web site, 1,000 products have been designated as orphan drugs, and 200 orphan products have been approved by the FDA. The law has been effective in encouraging manufacturers to develop products for rare disease.
Prescription Drug Marketing Act (PDMA) of 1987 and Prescription Drug Amendments of 1992: The PDMA was passed by Congress in 1987 "because there were insufficient safeguards in the prescription drug distribution system to prevent the introduction and retail sale of substandard, ineffective, or counterfeit drugs and that a wholesale drug diversion submarket had developed that prevented effective control over, or even routine knowledge of, the true sources of the drug." Congress also expressed concern that samples provided to doctors were being sold to consumers rather than freely distributed as intended by drug manufacturers. The PDMA was amended in 1992.
- Consistent with these concerns, the PDMA requires companies to account for disposition of drug samples and prohibits reimportation of drugs exported to other countries (Prescription Drug Marketing Act: Report to Congress, 2001; Hyman, 1998). Samples or donated pharmaceutical products generally cannot be sold to consumers. If a company becomes aware that a product has been stolen or that there is a "significant loss" of product, it should conduct an investigation and report the situation to the FDA within 5 days.
- The PDMA also impacts the distribution and storage of drugs by imposing certain requirements on wholesalers, such as ensuring that drugs are stored securely and that wholesalers provide the name and lot number of the drug to purchasers. According to the FDA report, wholesalers who "serve as middlemen between drug manufacturers and prescription drug dispensers" such as CVS and other retail pharmacies are supposed to be licensed by the states pursuant to FDA requirements.
Prescription Drug User Fee Act (PDUFA) of 1992 (reauthorized in 1997 and 2002): Allows the FDA to accept user fees from drug and biologic companies in return for committing to review new drug and biologic products within certain time frames. PDUFA has been credited with speeding the approval of new products but some critics believe that more needs to be done to monitor the safety of new drugs after approval and to ensure that receiving industry user fees does not create a "conflict of interest" for the FDA when reviewing drug products (Effect of user fees on drug approval times, withdrawals, and other agency activities, 2002; Statement of Peter Lurie, 2002). The third enactment of PDUFA, passed as part of the Public Health and Bioterrorism Preparedness Act, committed additional resources for postmarket monitoring of new products and allows the FDA to hire additional personnel to review drug and biologic products.
Mammography Quality Standards Act of 1992 (reauthorized 1998): Provides for the FDA to ensure that mammography facilities are certified and inspected. Facilities providing mammograms must hire adequately trained personnel and use high-quality equipment. Facilities also must be certified by 1 of 4 states or by the American College of Radiology. There are more than 9,500 such facilities in the United States. The FDA conducts yearly inspections of federal mammography facilities and some state mammography facilities. In 45 states, state personnel under contract with the FDA inspect mammography facilities. Facilities must pay user fees to reimburse the FDA for the cost of conducting inspections. A list of certified mammography facilities can be viewed on the FDA's Web site. The FDA’s Center for Devices and Radiological Health (CDRH) bears responsibility for the agency’s mammography regulation efforts.
Nutrition Labeling and Education Act (NLEA) of 1990: The NLEA allowed the use of FDA-approved health claims on food labels and required a uniform format for labels that includes serving size, contents, calories, nutrients, and the recommended daily allowance of nutrients for which such daily values have been established; lists of ingredients, and the number of servings per container. Certain foods such as those served in restaurants are exempt from these requirements. Because of the NLEA, dietary supplement manufacturers now can make health claims without being considered drugs.
Dietary Supplement Health and Education Act (DSHEA) of 1994: Dietary supplements defined as vitamins, herbs, and minerals are exempt from food additive provisions. This means that the FDA must prove the supplements are unsafe as opposed to manufacturers' having to demonstrate the safety of these products. DSHEA established labeling requirements, allowed "nutritional support statements" describing the effect of a supplement, and provided for the FDA to issue good manufacturing practice regulations for the dietary supplement industry. Before DSHEA, supplements were regulated in the same way as foods, food ingredients, or food additives.
Good Manufacturing Practice regulations for the dietary supplement industry will be published by the FDA in the near future (Secretary Thompson Urges Strong Warning Labels for Ephedra, 2002). The regulations will require supplement manufacturers to submit to FDA inspections and "assure potency, purity, and consistency in dietary supplement products" (Center for Food Safety and Applied Nutrition, 2002).
Food and Drug Modernization Act (FDAMA) of 1997: FDAMA established fast-track approval for certain new drugs and accelerated approval for innovative devices by exempting certain devices from premarket notification requirements. The Act also allowed the FDA to use expert panels in the drug approval process, regulated health claims in food, reauthorized the Prescription Drug User Fee Act, and provided additional marketing exclusivity time to companies that conducted pediatric studies.