Box 2.

1 Regulatory Changes following the

Thalidomide Tragedy
Key provisions of The Kefauver–Harris Amendments
(P.L. 87-781, October 10, 1962)

• Required affirmative approval from the FDA

before a product could be marketed 21 Code

of Federal Regulations (CFR) § 314). • Instituted a mandatory investigational new

drug process permitting FDA monitoring of
testing, transportation, and distribution (21

CFR § 312). • Mandated registration of subjects exposed

during pre-clinical and clinical testing (21

CFR § 50). • Established three separate phases of clinical

trials to prove efficacy (21 CFR § 312). • Required uniformly formatted drug labeling
(21 CFR § 201.57). Labeling must contain:
– a summary of all information learned
about the drug testing;
– pharmacology;
– contraindications;
– warnings;
– precautions;
– AEs seen;

– dosing and administration. • Established good manufacturing practices

(21 CFR § 210). • Mandatory safety monitoring and reporting
requirements for reports received by manufacturers

(21 CFR § 314.80). • Regular postmarketing communication with

FDA on experience with the drug (21 CFR §
314.81), including:
– sales;
– all spontaneous reports;
– analysis of medical literature on product