Federal regulation of biologics began more than 100 years ago with the enactment of the Biologics Control Act of 1902. That
act required licensing of establishments to manufacture and sell vaccines, sera, antitoxins, and other similar products in
order to prevent deaths from contaminated vaccines, as had recently occurred with the diphtheria antitoxin. The Federal Food
and Drugs Act of 1906, and the Food, Drug, and Cosmetics Act of 1938 provided additional authority for ensuring the safety
and quality of drugs and biologics through product testing and manufacturing inspections.
When the first issue of BioPharm International appeared 20 years ago, the US Food and Drug Administration (FDA) had assumed responsibility for overseeing biotechnology
therapies (see sidebar). Its Center for Biologics Evaluation and Research (CBER) was responding to new challenges posed by
the emergence of recombinant DNA products and gene therapies. The genomics and proteomics revolutions were just beginning,
promising new biomedical discoveries that would transform human healthcare.
From Laboratory to Complex Center
The 1980s were a time of considerable change and expansion at the regulatory agency. The acquired immunodeficiency syndrome
(AIDS) epidemic highlighted the need to ensure a safe blood supply while also spurring patient demands for faster access to
promising therapies. The thalidomide crisis of the 1960s had imposed a cautious approach at the agency, but AIDS encouraged
officials to acknowledge that their job was to facilitate the development of needed treatments, and to guard against unsafe
products. The FDA established new rules in the mid-1980s that made it easier for patients with serious conditions to access
experimental therapies. Other policies were established at this time that reshaped biomedical R&D. Some policies included
are listed below.
Human Research Protections
The FDA and other federal agencies involved in medical research revised regulations protecting individuals participating in
clinical trials based on the 1979 Belmont Report. Over the next decade, more government agencies adopted the "Common Rule"
governing human subject research, which requires researchers to obtain and document informed consent; provides special protections
for children, women, and prisoners; and sets policies for institutional review boards.
Orphan Drug Development
Congress passed the Orphan Drug Act in 1983, launching an innovative program to encourage the development of treatments for
rare diseases. The legislation provides extended market exclusivity for drugs and medical products that treat diseases affecting
fewer than 200,000 people in the US and awards grants to support orphan drug clinical trials. These incentives have led to
FDA approval of nearly 300 drugs and biological products.
The FDA joined with regulators and manufacturers from Europe and Japan in 1990 to establish the International Conference on
Harmonization (ICH). The ICH established a formal process for developing common standards and policies for testing and registering
new drugs and biologics in the three regions.
Support from User Fees
David Kessler became FDA commissioner in 1990 and moved to crack down on fraud and abuse and establish a more efficient FDA
review process. Kessler supported the Prescription Drug User Fee Act of 1992, which requires manufacturers of drugs and biologics
to pay fees to obtain timely assessments of market applications and supplements. A five-year "sunset" provision required reauthorization
of the user fee program in 1997, 2002, and 2007.
In renewing the user fee program in 1997 (PDUFA II), Congress enacted the FDA Modernization Act (FDAMA), which revised and
extended many agency programs. It clarified and streamlined policies governing clinical research, application review procedures,
marketing rules, and postmarketing surveillance requirements. Key provisions simplified rules for documenting and reporting
manufacturing changes to approved drugs and biologics, and set the stage for eliminating licenses for manufacturing facilities
and lot release requirements for biotech therapeutics.
MODERN MANUFACTURING AND REGULATION
As it celebrated 100 years of biotech regulation in 2002, the FDA launched a major initiative to update the rules governing
good manufacturing practices (GMPs) for drugs and biologics. The program calls for a more risk-based system for inspecting
manufacturing facilities and for ensuring product quality. The ultimate goal is to reduce agency oversight of manufacturing
processes and postapproval changes, and to provide regulatory flexibility for companies to be able to establish quality control