1962: Kefauver-Harris Drug Amendment (1962)

In the wake of the thalidomide catastrophe, US Senator Estes Kefauver and Representative Oren
Harris championed a sweeping amendment to the 1938 Federal Food, Drug, and Cosmetic Act. Signed
into law by President John F. Kennedy on 10 October 1962, the Kefauver-Harris Amendments
fundamentally reformed drug regulation in the United States.

The central innovation of the amendment was the requirement that drug manufacturers demonstrate
not only safety but also efficacy through "substantial evidence" from "adequate and well-controlled
investigations"—in practice, from randomised controlled clinical trials. This requirement applied
retroactively: the FDA was directed to evaluate the approximately 4,000 drugs approved between
1938 and 1962 for efficacy, a massive undertaking implemented through the Drug Efficacy Study
Implementation (DESI) programme that ultimately withdrew or relabelled hundreds of products.

Additional provisions included: informed consent requirements for investigational drug subjects;
mandatory reporting of adverse drug reactions by manufacturers; FDA control over drug advertising;
requirement that manufacturing processes meet current Good Manufacturing Practice (cGMP); and
strengthened FDA authority over clinical investigations.

The amendment also introduced the Investigational New Drug (IND) application process, requiring
manufacturers to notify the FDA before beginning human trials and allowing the agency to place a
clinical hold on investigations where safety risks were unacceptable.

Together with the 1938 FD&C Act and the thalidomide tragedy that prompted the amendment, 1962
marks the foundation of the modern drug approval paradigm: safety demonstrated in animals,
then humans; efficacy proven by RCTs; and continuous post-market surveillance.