Drug regulation 1906–1962

Early in this century, fraud was rampant among the producers of foods and drugs in the United States. Harvey W. Wiley, then chief of the Bureau of Chemistry of the U.S. Department of Agriculture, undertook a vigorous campaign against the unscrupulous practices of both industries. His work resulted in passage of the Food and Drugs Act of 1906. Commonly but incorrectly referred to as the “Pure Food and Drug” Act, the statute was, at the time, a true innovation. This act and the 1912 Sherley amendment to it put an end to many fraudulent practices, such as the misbranding and adulteration of drugs, but failed to address effectively the problems

of drug safety and efficacy. 1 Little attention was paid to such matters for more than thirty years; then, a tragedy brought drug safety concerns to the fore.

In 1937 the S. E. Massengill Company of Bristol, Tennessee, began to market an Elixir Sulfanilamide consisting of 8.8 percent of the drug in 72 percent diethylene glycol. This product, intended primarily for Southerners who liked to drink their medicines, was marketed without adequate toxicity testing in animals; in fact, it was tested only for flavor prior to marketing. Before the poisonous character of the solvent was recognized and the product could be recalled, it caused some 105 deaths

from acute kidney failure. 2 The public outcry resulting from this unfortu- nate episode precipitated the passage of the 1938 Federal Food, Drug, and

224 Appendix: The herbal regulatory system Cosmetic Act. Among its requirements was one necessitating that drugs

entering interstate commerce be proven safe. If a drug already on the market was subject to the 1906 act, it was grandfathered, and additional proof of safety was not required.

Although a number of amendments were made to the 1938 act, includ- ing a rather significant one (Durham–Humphrey) in 1951 that dealt largely with classification and procedures, it took a further tragedy to bring about substantial change. Thalidomide, a sedative drug developed by Chemie Grunenthal GmbH in Stolberg, Germany, in 1953 and widely marketed in Europe, was identified in 1962 as a potent teratogen. About 30–40 percent of the mothers who took the drug during a critical phase of their pregnancies gave birth to physically deformed babies. The drug was briefly marketed in Canada with disastrous effect. Thalidomide was never marketed in the United States, but its observed side effects caused great concern there. 3

This period of alarm coincided with an extensive Congressional investigation of the American drug industry led by Senator Estes Kefauver of Tennessee. All of these events resulted in the passage of the Drug Amendments of 1962, often referred to as the Kefauver–Harris Amendments. These required, among other things, that all drugs marketed in the United States after 1962 be proven both safe and effective. Again, drugs marketed prior to 1938 were grandfathered, but every product introduced between 1938 and 1962 was subject to these requirements. This group consisted of approximately three hundred different chemical enti- ties in about four thousand different drug formulations that were actively being sold, as well as another three thousand formulations that had been approved by the standard new drug application (NDA) process but were not actively marketed.

Drug regulation 1906–1962