The FDA is a governmental creation responding to the need for public safety with respect to foods and medicines. The majority of important legislative acts in the history of the FDA have come following specific instances requiring action.

The first United States federal law enacted to improve the health and ensure the safety of the healthcare consumer was the Vaccine Act if 1813. The Act was repealed in 1922 after a regional outbreak of smallpox from contaminated vaccine. In 1902, the Biologics Control Act was enacted in response to the death of 13 children in St. Louis due to tainted diphtheria antitoxin. The Act provided regulations governing all aspects of commercial production of vaccines, serums, toxins, antitoxins, and similar products with the objective to ensure safety, purity, and potency. It required a Product License Application (PLA) and an Establishment License Application (ELA) before a biologic product could be marketed in interstate commerce.

Prior to 1906 most drugs, medical devices and therapies were “patented medicines” and therefore trade secrets. This allowed peddlers of “magic elixirs” and so forth to sell products not proven safe or effective. In 1906 the Pure Food and Drug Act was passed which regulated only product labeling. A product promoter could make therapeutic claims, as long as the label identified an accurate list of contents. Also known as Wiley’s Act, after Dr. Harvey Wiley, chief chemist for the Bureau of Chemistry, then a part of the USDA, the FDA Act responded to the abhorrent conditions chronicled in Upton Sinclair’s The Jungle about America’s meat industry. However, this was not the first drug related Act in FDA history.

As early as 1848, the Drug Importation Act became law after American soldiers were affected by adulterated quinine, an anti-malaria drug, while serving in Mexico. It required laboratory inspections, detention and even destruction of drugs that did not meet standards.

The Sherley Amendment of 1912 prohibited the labeling of medications with false therapeutic claims. Congress passed this legislation in response to the 1910 seizure of a worthless product called Johnson's Mild Combination Treatment for Cancer, and because the U.S. Supreme Court in U.S. v. Johnson ruled against the government, finding that the product's false claims for effectiveness were not within the scope of the Pure Food and Drugs Act. Just shortly after in 1914 the Harrison Narcotic Act eliminated the use of opiates in the teething syrups of babies resulting in addiction and death.

The Sulfanilamide tragedy of 1937 that resulted in 107 deaths, mostly children, spurred the enactment of The Federal Food, Drug and Cosmetic Act of 1938 (FDCA). The deaths were caused when the S.E. Massingill company used diethylene glycol (anti-freeze) to solubilize the sulfa used in the product. The new Act repealed the Sherley Amendment and required all new drugs be tested by the manufacturer for safety and those tests filed with the government for marketing approval via a New Drug Application. Further, the Act prohibited interstate commerce of products considered misbranded and allowed the use of injunctions in addition to penalties of seizure and prosecution.

In 1944, the Public Health Service Act brought coverage to several health concerns and regulated biologic product. The following year in 1945, the Insulin Amendment Act required FDA to test and certify the purity and potency of insulin. In 1951, the Durham-Humphrey Amendment defined the kinds of drugs that cannot be safely used without medical supervision and restricted their sale to prescription by a licensed practitioner. In 1958, the Food Additives Amendment required safety standards for additives, and FDA published “Substances Generally Recognized as Safe” (GRAS). In 1960, the Color Additive Amendment required testing to establish safety of color additives in drugs, foods and cosmetics.

The next major legislation derived from the tragedy associated with the drug Thalidomide. The drug was prescribed to pregnant women in the late 1950’s in Europe and Canada, and as a result, babies were born with a condition known as phocomelia, a defect where the limbs resemble flippers. The drug was not approved at the time in the U.S. thanks to FDA’s chief medical officer Dr. Francis Kelsey who stalled approval because of safety issues. The Kefauver-Harris Act of 1962 amended the FDCA. It required drug manufacturers to prove safety and efficacy, register with FDA, be inspected every two years, have prescription drug advertising approved by FDA, and provide and obtain informed consent from subjects prior to clinical trials.

In 1966, FDA contracted with the National Academy of Sciences and the National Research Council to examine drugs approved between 1938 and 1962 based on safety alone. This was the DESI Act (Drug Efficacy Study Implementation Review) which brought about determinations of whether post-1938 drugs were effective. Also in 1966, there was the Fair Packaging and Labeling Act that required honest and informative labeling of consumer products in interstate commerce. FDA now enforces the provisions on foods, drugs, cosmetics, and medical devices.

In 1972, FDA began reviewing over-the-counter products. At the time, over 300,000 products were on the market, and FDA enlisted advisory panels to help with this daunting task. As a result, a monograph was created identifying acceptable active ingredients and labeling in the 80 defined therapeutic categories. It took FDA almost 20 years to complete this review. With respect to medical devices, in 1976 the Medical Device Amendments were passed in response to the serious adverse events seen with the Dalkon Shield IUD that was withdrawn from the market just two years earlier. The Amendments established the current risk classifications for medical devices as well as a requirement for “device GMPs”.

The Orphan Drug Act was established in 1983. The Act’s design was to entice drug manufacturers to develop and promote drugs for diseases affecting less than 200,000 persons. Sponsors who developed products for these diseases were granted seven years exclusivity, tax exempt clinical trials, and scientific advice. The following year in 1984 the Price Competition and Patent Restoration Act otherwise known as the Waxman-Hatch Act was enacted. This Act consisted of two Titles, the first addressing generic pharmaceuticals and the second for aiding and encouraging research by extending patent life for innovator drugs while under FDA review. In 1986, there was the Childhood Vaccine Act which required patient information on vaccines and provided FDA the authority to recall biologics and impose civil penalties.

In 1990, the Safe Medical Devices Act expanded the Medical Devices Amendment and required post-market surveillance and tracking for certain implanted devices, authorized FDA to order device recalls and impose civil penalties on manufacturers, and required user facilities to report device adverse events. In 1992, the first of four Prescription Drug User Fee Acts were enacted. The acts were designed to increase funding to FDA and decrease review times through additional staffing and modernization. In 1996, the medical device GMPs were restructured along the lines of ISO 9001; they were then renamed the Quality Systems Regulations. The FDA Design Control guidance was also released this year. In 1997, the FDA Modernization Act not only extended user fees, but provided six months extra exclusivity for pediatric studies, created a clinical trials data bank, expanded access to investigational therapies, and provided for fast track drug approvals.

In 2002, the current Good Manufacturing Practice (cGMP) initiative enhanced and updated regulation of manufacturing processes and end-product quality of animal and human drugs and biological medicines. In the same year, the Best Pharmaceuticals for Children Act was passed to improve safety and efficacy of patented and off-patent medicines for children, and continued the exclusivity provisions for pediatric drugs started under FDAMA. Also in 2002, the Medical Device User Fee and Modernization Act required user fees like for drugs, but also allowed third party inspections, and required reprocessors of some exempt devices and single use devices to submit 510K’s or premarket reports. The following year, in 2003, the Pediatric Research Equity Act required pediatric assessment for NDAs and BLAs, unless a waiver was obtained. And, in 2004, the Project Bioshield Act authorized FDA to stockpile vaccines and drugs to fight bioterrorism agents.

The FDA continues to expand its coverage in the pursuit of consumer safety. Proactive initiatives are continually being evaluated, but with the ever-changing landscape of pharmaceutical, biologic and medical device development it will be difficult to avert all adverse events. Responsive action will be a mainstay in FDA and with it so will the history of FDA continue to grow.

We are often asked – What is the FDA? We hope this essay has helped to show the FDA is a science regulating government organization that keeps adapting to the medical problems of contemporary American society.