A fast-expanding pharmaceutical industry also was attracting public attention because of high drug prices, fairly rudimentary
clinical-research activities, and increasingly bold claims in drug labeling and advertising. Senator Estes Kefauver began
to hold hearings in 1960 on proposals to strengthen FDA oversight, including new rules for monitoring manufacturing practices.
The bill was going nowhere, though, until the horrifying effects of thalidomide on newborns became known in 1962. FDA reviewer
Frances Kelsey had qualms about the NDA for the product, and her hesitation made her a hero overnight. The narrowly avoided
tragedy prompted Congress to adopt the Kefauver–Harris Amendments, which required drug manufacturers to prove that products
are both safe and effective before marketing. The measure also formalized good manufacturing practices (GMPs), required adverse-event
reporting, and called for sponsors of clinical trials to obtain informed consent from study participants.
These new requirements prompted a major expansion of FDA's Division of New Drugs, forming separate branches to evaluate NDAs
and to monitor clinical trials, manufacturing controls, and adverse-reaction reports. The National Center for Drug Analysis
opened in St. Louis in 1967 to conduct large-scale tests of drug products. The Bureau of Drugs became the Bureau of Drugs
and Biologics in 1980 to coordinate agency oversight better, but the combination proved unwieldy and lasted only a few years
(see sidebar, "Challenges for CDER").
Another major initiative was to assess the safety and efficacy of the vast number of drugs already on the market that never
had been formally evaluated for efficacy. The resulting Drug Efficacy Study Implementation (DESI) review of some 3500 products
lasted almost 20 years. In 1972, FDA launched a similar retrospective review of over-the-counter drugs that led to monographs
on the safety and efficacy of some 1000 active ingredients.
AIDS revolution
The 1980s were a time of important social and biomedical change in the United States that entailed major consequences for
FDA. The first reports of AIDS appeared in 1981, prompting coordinated efforts by FDA and researchers to develop and approve
immunoassay tests. Azidothymidine (AZT), the first drug to treat AIDS, was approved by FDA in 1987, along with additional
treatments for certain opportunistic infections.
In addition, demands from well-informed AIDS patient advocates for faster access to promising therapies spurred a general
rethinking of FDA regulatory attitudes. The thalidomide crisis had fostered a cautious approach at the agency, but the AIDS
epidemic engendered a less risk-averse attitude. FDA revised rules to expand access to experimental drugs for severely ill
patients and to permit market approval of AIDS and cancer treatments based on preliminary clinical results.
The need for biomedical innovation also built support for an innovative program to encourage the development of treatments
for rare diseases. Congress approved the Orphan Drug Act in 1983, which extends market exclusivity for drugs and medical products
that treat diseases affecting less than 200,000 people in the United States and has led to the approval of nearly 300 drugs
and biologics.
Generics spur competition
In 1984, Congress established the basis for the modern generic drug industry with the enactment of the Drug Price Competition
and Patent Term Restoration Act, commonly known as the Hatch–Waxman Act. The bill allowed FDA to approve abbreviated applications
for identical versions of brand-name drugs on the basis of preclinical and clinical testing performed by the innovator firm.
Early access to innovator research data allows generics companies to develop and test generics before patent expiration.
The trade-off for brand-name companies is as many as five years of additional patent protection for new medicines to make
up for time lost while their products went through FDA's approval process, which often ran for two or three years at that
time. Unfortunately, the legislation attracted some inexperienced operators to this fast-growing industry, leading to fraudulent
activities and a subsequent enforcement crackdown.
Monitoring distribution. In addition to illegal generic-drug activities, policymakers were increasingly concerned about questionable drug distribution
and marketing activities. Congress approved the Prescription Drug Marketing Act of 1988, which gave FDA added authority to
prevent drug diversion and resale by requiring industry to establish systems for tracking drugs and product samples. Specific
approaches for implementing the legislation have been hard to negotiate, however, and FDA is only now requiring some wholesalers
to establish pedigree systems to thwart sales of adulterated and counterfeit products.
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