Vaccine Licensure

Abstract

Vaccines must meet the highest standards for safety and efficacy, as they are used for prevention of diseases in healthy subjects, not as treatment for disease. Vaccines are biological products (live or inactivated whole microorganisms or extracts thereof, sometimes heterogenous composition, sensitive to manufacturing conditions, etc.), and thus by their nature they are different from other medicines. The licensing process itself – from development and manufacturing to evaluation of safety and effectiveness post licensure – are the product: “Development and production processes are the licensed product.” In the USA, licensing granted by the FDA encompasses two phases: an “Investigational New Drug” (IND-) phase” and a “Biologics License Application (BLA-) phase” with defined timelines and procedures. There are several ways to accelerate vaccine development and licensing if it is of high public health interest. To support licensure, efficacy must usually be shown by disease reduction in high-quality randomized controlled clinical trials (RCTs). Alternatively, licensure can be obtained based on RCTs using a validated “correlate of protection”, or animal studies if human clinical studies are not feasible. A “surrogate of protection” that is reasonably likely to predict clinical benefit may be used to support conditional licensure under the Accelerated Approval pathway with a commitment to conduct a clinical endpoint efficacy study as a post-approval commitment. For the European Union (EU) and the three European Economic Area (EEA) states, the European Medicines Agency (EMA) is responsible for vaccine licensure. Here vaccines can be licensed by a (1) Centralized Procedure, (2) Mutual Recognition, (3) Decentralized Procedure, or (4) National Procedure. In addition, for licensed vaccines, “WHO prequalification” offers a way to provide existing affordable, safe, and effective vaccines to resource-poor countries.