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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.
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.
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.
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.
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.
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 systems.
Other important programs launched in recent years are reflected in the following:
The FDA established the Office of Combination Products in 2002 to manage market applications from a growing number of medical products that combine drugs, biologics, and medical devices.
In the wake of 9/11, Congress approved legislation to strengthen controls on imported products. The Project BioShield Act of 2004 encouraged the development and regulation of drugs and vaccines to prevent or treat bioterrorist threats, a policy reinforced by additional legislation in 2006. CBER has played a lead role in spurring the development of new vaccines and updating production methods to provide preventives and treatments for infectious diseases and biological attack.
The FDA issued the Critical Path report in March 2004 urging novel approaches for bringing new therapies to patients. This launched a major effort to encourage FDA collaboration with the industry to counter a decline in new therapies. In 2006, the agency issued an Opportunities List of a wide range of research and regulatory initiatives with potential to lead to biomedical discovery.
In 2005, the FDA issued requirements for manufacturers to submit drug labeling in electronic format to the Daily Med data bank. The regulations also revised the format of labeling for human prescription drugs and biological products to include a highlights section, making the information easier to access and use.
Regulators and manufacturers are optimistic that recent discoveries in genomic sciences and molecular biology will create opportunities to develop entire new classes of more effective and less toxic medicines, potentially at low costs. Cooperative efforts to adopt new regulatory models in harmony with the approaches of other cultures and nations may streamline drug development and registration, and accelerate global access to new therapies.
Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634, firstname.lastname@example.org