U.S. Drug Safety Roots, and the FDA

25571Up until the 20th century, there were few federal laws regulating the contents and sale of domestically produced food and pharmaceuticals. The history of the Food and Drug Administration (FDA) can be traced to the latter part of the 19th century and the U.S. Department of Agriculture’s Division of Chemistry. Under Harvey Wiley, the Division began conducting research into the adulteration and misbranding of food and drugs on the American market. In result, increasing federal regulations in matters pertinent to public safety.

In June 1906, President Roosevelt signed into law the Food and Drug Act, also known as the “Wiley Act” after its chief advocate. The Act prohibited, under penalty of seizure of goods, the interstate transport of food that had been “adulterated”. The act applied similar penalties to the interstate marketing of “adulterated” drugs, in which the “standard of strength, quality, or purity” of the active ingredient was not either stated clearly on the label or listed in the United States Pharmacopoeia or the National Formulary. The responsibility for examining food and drugs for such “adulteration” or “misbranding” was given to Wiley’s USDA Bureau of Chemistry. In 1927, the Bureau of Chemistry’s regulatory powers were reorganized under a new USDA body, the Food, Drug, and Insecticide organization. This name was shortened to the Food and Drug Administration (FDA) three years later.

Public outcry over the 1937 Elixir Sulfanilamide tragedy, in which over 100 people died after using a drug formulated with a toxic, untested solvent. President Roosevelt signed the new Food Drug and Cosmetic Act (FD&C Act) into law on June 24, 1938, formally called the Code of Federal Regulation (CFR), Title 21 Food and Drugs, Chapter 1 Food and Drug Administration (FDA). The new law significantly increased federal regulatory authority over drugs by mandating a pre-market review of the safety of all new drugs, as well as banning false therapeutic claims in drug labeling without requiring that the FDA prove fraudulent intent. Soon after passage of the 1938 Act, the FDA began to designate certain drugs as safe for use only under the supervision of a medical professional, and the category of “prescription only” drugs was securely codified into law by the 1951. These developments confirmed extensive powers for the FDA to enforce post-marketing recalls of ineffective drugs.

In 1959, the thalidomide tragedy, in which thousands of European babies were born deformed after their mothers took that drug – marketed for treatment of nausea – during their pregnancies, led to the 1962 Kefauver-Harris Amendment to the FD&C Act, which represented a “revolution” in FDA regulatory authority. The most important change was the requirement that all new drug applications demonstrate “substantial evidence” of the drug’s efficacy for a marketed indication, in addition to the existing requirement for pre-marketing demonstration of safety. This marked the start of the FDA approval process in its modern form.

Around this time, the World Medical Association (WMA) developed the Declaration of Helsinki as a statement of ethical principles for medical research involving human subjects including research on identifiable human material and data. The primary purpose of medical research involving human subjects is to understand the causes, development and effects of diseases and improve preventive, diagnostic and therapeutic interventions (methods, procedures and treatments). Even the best current interventions must be evaluated continually through research for their safety, effectiveness, efficiency, accessibility and quality.

These reforms had the effect of increasing the time required to bring a drug to market. Concerns about the length of the drug approval process were brought to the fore early in the AIDS epidemic. In response the FDA issued new rules to expedite approval of drugs for life threatening diseases, and expanded pre-approval access to drugs for patients with limited treatment options. This has led to the call for more robust and enduring reforms that would allow patients, under the care of their doctors, access to drugs that have passed the first round of clinical trials.  Since the 1990s, many successful new drugs for the treatment of cancer, autoimmune diseases, and other conditions have been protein-based biotechnology drugs, regulated by the Center for Biologics Evaluation Research (CBER). CBER along with the Centers for Drug Evaluation and Research (CDER) are important organizations that make up the FDA which is organized under the US Department of Health and Human Services (HHS). The first draft of the Guidance for Industry which later evolved into the Good Clinical Practices was established by the CDER.