Which act or amendment created the separation of drugs into two different categories, prescription (legend) and OTC?

The Durham-Humphrey Amendment is the legislation responsible for establishing the distinction between prescription drugs (often referred to as legend drugs) and over-the-counter (OTC) medications. Enacted in 1951, this amendment to the Federal Food, Drug, and Cosmetic Act clarified the criteria for drug dispensing and the role of healthcare professionals in the prescription process. It allowed for the classification of certain drugs to require a prescription based on their safety and potential for misuse, while others could be made available directly to consumers without the need for a prescription. This separation was essential for consumer safety, ensuring that more potent or potentially dangerous medications were used under the guidance of a licensed practitioner.

The other options, while significant in their own right, do not pertain to the establishment of the prescription versus OTC distinction. The Kefauver-Harris Amendment focused primarily on drug efficacy and safety, the Pure Food and Drug Act targeted adulterated and misbranded foods and drugs without creating such a classification, and the Food, Drug, and Cosmetic Act provided a broad regulatory framework for food and drugs, but it was the Durham-Humphrey Amendment that specifically delineated the different categories of drugs.