Continuing the federal laws related to pharmaceuticals and the FDA, this week, we present the Durham-Humphrey Amendment of 1951 and the Kefauver-Harris Amendments of 1962.

Durham-Humphrey Amendment of 1951
The Durham-Humphrey Amendment of the Federal Food Drug and Cosmetic Act established a legal distinction between prescription and over-the-counter (OTC) or nonprescription drugs.

Medications deemed safe enough by the FDA for self-treatment are made available to consumers for direct purchase whereas medications requiring professional diagnosis for their safe and effective use must be dispensed only upon a valid prescription or institutional medication order. Prescription drugs must bear the symbol "Rx Only" or the legend "Caution: Federal Law Prohibits Dispensing Without Prescription." New drug substances are limited to prescription-only dispensing. However, their legal status may be changed to OTC, albeit usually at lower recommended dosage, should they later be considered useful and safe enough for the lay person's discretionary use. Examples of such drugs include cimetidine, ibuprofen, ketoprofen, loratadine, omeprazole and ranitidine.

According to the Durham-Humphrey Amendment, prescriptions for legend drugs may not be refilled (dispensed again after the initial filling of the prescription) without the express consent of the prescriber. The refill status of prescriptions for certain legend drugs known to be subject to public abuse was further regulated with the passage of the Drug Abuse Control Amendments of 1965 and then by the Comprehensive Drug Abuse Prevention and Control Act of 1970.

Kefauver-Harris Amendments of 1962

A tragedy in 1960 led to the passage of the Kefauver-Harris Amendments to the Federal Food Drug and Cosmetic Act of 1938. A new synthetic drug, thalidomide, recommended as a sedative and tranquilizer, was being sold OTC in Europe. It was a drug of special interest because of its apparent lack of toxicity even at extreme dosage levels. It was hoped that it would replace the barbiturates as a sedative and therefore prevent the frequent deaths caused from accidental and intentional barbiturate overdosage.

A pharmaceutical company was awaiting FDA approval for marketing in the United States when reports of a toxic effect of the drug's use in Europe began to appear. Thalidomide given to women during pregnancy produced birth defects, most notably phocomelia, an arrested development of the limbs of the affected newborn. Thousands of children were affected to various extents. Some were born without arms or legs and others, with partially formed limbs. The more fortunate were born with only disfigurations of the nose, eyes, and ears. The most severely afflicted died of malformation of the heart or gastrointestinal tract. This drug catastrophe spurred the Congress to strengthen the existing laws regarding new drugs. Without dissent, on October 10, 1962, the Kefauver-Harris Drug Amendments to the Food, Drug, and Cosmetic Act of 1938 were passed by both houses of Congress. The purpose of the enactment was to ensure a greater degree of safety for approved drugs, and manufacturers were now required to prove a drug both safe and effective before it would be granted FDA approval for marketing.

Under the Food, Drug, and Cosmetic Act as amended, the sponsor of a new drug is required to file an investigational new drug application (IND) with the FDA before the drug may be clinically tested on human subjects. Only after carefully designed and structured human clinical trials, in which the drug is evaluated for safety and effectiveness, may the drug's sponsor file an NDA seeking approval for marketing.

The FDA was given authority to issue good manufacturing practice (GMP) guidelines governing how drugs were to be manufactured, access to facilities for inspection, and jurisdiction over prescription drug advertising. Interestingly, WHO now considers thalidomide to be the standard treatment for the fever and painful skin lesions associated with erythema nodosum leprosum (ENL) in patients with leprosy and the FDA has approved its use for this purpose. Further, research into potential uses for thalidomide has determined that it is effective in the treatment of multiple myeloma, a blood and bone marrow cancer, and shows promise in certain inflammatory diseases, and in Kaposi sarcoma, a cancer of the blood vessel walls mostly found in people with HIV.

Next week, we will look at the Food and Drug Administration Modernization Act of 1997 and the Food and Drug Administration Amendments Act of 2007.

Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
IJPC
Remington: The Science and Practice of Pharmacy Twenty-second edition