In 1937, sulfanilamide, the first sulfa antimicrobial drug, was marketed. The diluent for this sulfa preparation was diethylene glycol, a chemical analog of antifreeze. More than 100 people, many of whom were children, died after receiving the drug. As a result, the US Congress enacted the 1938 Federal Food, Drug and Cosmetic Act, which required proof of safety before the introduction of a new drug into clinical practice. This act also changed the focus of the FDA from a policing agency, with an emphasis on confiscation of adulterated drugs, to a regulatory agency supervising the evaluation of new drugs.
In the practice of pediatrics, drugs which are not approved by the Food and Drug Administration (FDA) as safe and effective in children are prescribed daily. This is due in part to the fact that many drugs released since 1962 carry an “orphaning clause” in the package insert such as, “not to be used in children, since clinical studies have been insufficient to establish recommendations for its use.” What is the status of the package insert? Is it a legal directive to the physician, or is it intended as a guide for the physician in prescribing a drug?
The package insert, by legal definition of the Federal Food, Drug and Cosmetic Act, is the official information piece for a drug. The information it contains is derived from data supplied by investigators and submitted by the pharmaceutical firm to the FDA. The insert is written and printed by the drug manufacturer, but its contents must be approved by the FDA. The Food, Drug and Cosmetic Act, as amended in 1962, requires full disclosure of all known facts pertaining to the use of the drug. Therefore, a great deal of information is included in the insert, including the chemical structure of the drug, a summary of its pharmacological and toxicological action, its clinical indications and contraindications, precautions, reported adverse reactions, dosage recommendations, and available dosage forms.