The Center for Biologics Evaluation and Research (CBER) is the division within the U.S. Food and Drug Administration (FDA) responsible for regulating biological products for human use. CBER works to ensure that these products are safe, pure, and potent before they reach the public. The agency’s mission is fundamentally linked to public health, overseeing everything from widely administered vaccines to cutting-edge cellular and gene therapies.
The Scope of Regulated Biologics
Biologics are fundamentally different from traditional pharmaceuticals, which are chemically synthesized small-molecule drugs. These products are derived from living organisms—human, animal, or microorganism sources—making them large, complex molecules that are not easily characterized or consistently reproduced. This complexity necessitates a distinct regulatory approach focused on controlling the entire production chain.
The range of products under CBER’s jurisdiction is broad. This includes preventative tools like vaccines and allergenic extracts used to treat allergies. It also covers therapeutic products such as blood and blood components, which are subject to stringent testing to ensure the safety of the nation’s blood supply.
CBER also regulates innovative treatments, including cellular therapies and gene therapies. Cellular therapies involve administering whole cells to patients, while gene therapies introduce genetic material to modify a person’s cells to treat a disease.
The Standard Approval Process
The process begins with preclinical research, where the product is studied in laboratory settings and animals to understand its mechanism of action and establish an initial safety profile. If these studies indicate a favorable risk profile, the manufacturer submits an Investigational New Drug (IND) application to CBER to request permission to begin human testing.
Clinical testing in humans is divided into three sequential phases. Phase 1 trials are small studies, often involving 20 to 80 healthy volunteers or patients, designed primarily to determine the product’s safety and dosage range. Phase 2 trials expand the study to a larger group of patients, typically a few hundred, to gather preliminary data on effectiveness and continue to evaluate safety.
The most extensive testing occurs in Phase 3, which involves hundreds to thousands of participants. Phase 3 is designed to confirm the product’s effectiveness and monitor for any less common side effects. Once all clinical trial data is collected and analyzed, the manufacturer submits a comprehensive Biologics License Application (BLA) to CBER. The BLA must include all data demonstrating the product’s safety, purity, and potency, along with detailed manufacturing information subject to facility inspections.
CBER’s review of a standard BLA typically takes 10 months. During this time, agency scientists and medical reviewers scrutinize the application’s scientific and clinical data. The agency evaluates whether the product’s benefits outweigh its risks for the intended patient population, and it may convene an advisory committee of external experts for an independent review. If the review is successful, CBER issues a license, authorizing the manufacturer to market the biologic.
Accelerated Review Pathways
For biologics that address serious or life-threatening conditions for which no satisfactory alternative treatment exists, CBER offers several specialized mechanisms to expedite the review process. The Priority Review designation, for instance, shortens the BLA review goal from 10 months to just 6 months for products that offer a significant improvement over existing treatments.
The Accelerated Approval pathway is reserved for products that demonstrate an effect on a “surrogate endpoint.” This is a laboratory measurement or physical sign that is reasonably likely to predict a long-term clinical benefit. This allows for earlier approval based on promising Phase 2 data, rather than waiting for the conclusive results of a lengthy Phase 3 trial. Approval through this mechanism requires the manufacturer to conduct mandatory post-marketing studies to confirm the anticipated clinical benefit.
Other programs like Fast Track and Breakthrough Therapy designations facilitate earlier and more frequent communication between the manufacturer and CBER throughout the development process. Breakthrough Therapy status is granted to products that show preliminary clinical evidence of substantial improvement over available therapy on a clinically significant endpoint.
Post-Market Safety Monitoring
CBER maintains continuous monitoring of a biologic after it is released for public use. Post-market surveillance is designed to detect rare or long-term adverse events that may not have been apparent during pre-market clinical trials. Manufacturers are required to submit periodic safety reports to CBER and must report any significant manufacturing or product problems.
The agency relies on reporting systems to capture real-world safety data from healthcare professionals and the public. For vaccines, adverse events are collected through the Vaccine Adverse Event Reporting System (VAERS), while other biologics utilize the MedWatch system. CBER scientists actively analyze these reports, looking for safety signals that may indicate a potential problem.
CBER also maintains control over the purity and potency of products through lot release protocols, particularly for vaccines. Manufacturers are required to conduct Phase 4, or post-marketing, studies to gather additional data or fulfill requirements established during an Accelerated Approval. If new safety concerns emerge, CBER has the authority to mandate labeling changes, restrict the product’s use, or withdraw the product’s licensure.