| The Food and Drug Administration�s (FDA) Center for Biologics Evaluation and
Research (CBER) is responsible for regulating vaccines in the United States. Current
authority for the regulation of vaccines resides primarily in Section 351 of the Public
Health Service Act and specific sections of the Federal Food, Drug and Cosmetic Act.
Vaccine clinical development follows the same general pathway as for drugs and other
biologics. A sponsor who wishes to begin clinical trials with a vaccine must submit an
Investigational New Drug application (IND) to the FDA. The IND describes the vaccine,
its method of manufacture, and the types of quality control testing done prior to
administering the vaccine to humans. Also included is information about the vaccine�s
safety and ability to elicit an immune response (immunogenicity) in animal testing. In
addition, the IND contains the proposed clinical protocol (written description of a
trial design) for a study in humans.
Pre-marketing (pre-licensure) vaccine clinical trials are typically done in three
phases, as is the case for any drug or biologic. Initial human studies, referred to as
Phase 1, are safety and immunogenicity studies performed in a small number of closely
monitored subjects. Phase 2 studies enroll up to hundreds of subjects. Phase 2 studies
often include dose-ranging studies (studies to evaluate the safety and immunogenicity of
different vaccine doses). Finally, Phase 3 trials typically enroll thousands of
individuals and provide the critical documentation of effectiveness and important
additional safety data required for licensing. At any stage of the clinical or animal
studies, if information provided to the FDA raises significant concerns about either
safety or effectiveness, the FDA may request additional information or studies, or may
halt ongoing clinical studies.
If successful, the completion of all three phases of clinical development can be
followed by the submission of a Biologics License Application (BLA). To be considered,
the license application must provide the multidisciplinary FDA reviewer team (composed
of many types of specialists including medical officers, microbiologists, chemists,
biostatisticians, etc.) with the efficacy and safety information necessary to make a
risk/benefit assessment and to recommend or oppose the approval of a vaccine. Also
during this stage, the proposed manufacturing facility undergoes a pre-approval
inspection during which production of the vaccine as it is in progress is examined in
detail.
Following the FDA�s review of a license application, the sponsor and the FDA may
present their findings to the FDA�s Vaccines and Related Biological Products Advisory
Committee (VRBPAC). This non-FDA expert committee (scientists, physicians,
biostatisticians, and a consumer representative) provides advice to the Agency regarding
the safety and efficacy of the vaccine for the proposed indication.
Vaccine approval also requires the provision of adequate product labeling to allow
health care providers to understand the vaccine�s proper use, including its potential
benefits and risks. This information allows health care providers to communicate with
patients and parents, and to safely deliver the vaccine to the public.
The FDA continues to monitor the production of vaccines after the vaccine and the
manufacturing processes are approved, in order to ensure continuing safety. After
licensure, monitoring of the product and of production activities, including periodic
facility inspections, must continue as long as the manufacturer holds a license for the
product. Manufacturers are required to submit the results of their own tests for
potency, safety, and purity for each vaccine lot to the FDA. They are also required to
submit samples of each vaccine lot to FDA for testing. However, if the sponsor describes
an alternative procedure which provides continued assurance of safety, purity and
potency, CBER may determine that routine submission of lot release protocols (showing
results of applicable tests) and samples is not necessary.
The process for approval of vaccines, as well as for drugs and other biologics, is
designed to ensure both the safety and effectiveness of the product. Each phase of the
pre-market clinical testing includes more people with each phase so that it becomes
easier to detect adverse events. However, until a vaccine is given to the general
population, all potential adverse events cannot be anticipated. Thus, many vaccines
undergo Phase 4 studies�formal studies on a vaccine once it is on the market. Also,
the government relies on the Vaccine Adverse Event Reporting System (VAERS) to identify
problems after marketing begins. The VAERS system and how it works is discussed further
on this website.
References:
National Vaccine Advisory Committee. "United States Vaccine Research: A Delicate
Fabric of Public and Private Collaboration." Pediatrics, Vol. 100 (6),
Dec. 1997, pp. 1015-1020.
Parkman PD, and MC Hardegree. "Regulation and Testing of Vaccines." In
Plotkin SA, Orenstein WA, [eds.]. Vaccines, 3d ed. Philadelphia: Saunders,
1999, pp.1131-1143.
Stehlin, Isadora. "How FDA Works to Ensure Vaccine Safety." FDA
Consumer Magazine, March 1996.
FDA, Center for Biologics and Research: http://www.fda.gov/cber/
Last updated: August 2001
|
