SAFETY IS A PRIORITY IN VACCINE DEVELOPMENT AND APPROVAL

Before vaccines are licensed by the United States Food and Drug Administration (FDA), they are tested extensively in the laboratory and with human subjects to ensure their safety. First, researchers use computers to predict how the vaccine will interact with the human immune system. Then researchers test the vaccine on animals including mice, guinea pigs, rabbits, and monkeys.

Vaccine development and approval 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 FDA. The IND describes the vaccine, its method of manufacture, and quality control tests for release. Also included are information about the vaccine’s safety and ability to elicit a protective immune response (immunogenicity) in animal testing, as well as a proposed plan for testing the drug on humans.

FDA reviews the IND to ensure a vaccine’s use in clinical studies does not place human subjects at unreasonable risk of harm, and adequate informed consent and human subject protections are in place. Participation in these studies is completely voluntary. Many individuals choose to contribute their time and energy for the advancement of science. Before they participate in research, all participants must demonstrate that they understand the purpose of the study and its potential risks. Volunteers agree to receive the vaccine and undergo any medical testing necessary to assess its safety and efficacy.

Vaccine licensing is a lengthy process that can take 10 years or longer. The FDA requires that vaccines undergo three phases of clinical trials with human subjects before they can be licensed for use in the general public:

Phase 1 Clinical Trials

Clinical trials are small, involving only 20 to 100 volunteers, and last only a few months. The purpose of phase one trials is to evaluate basic safety and identify very common reactions.

Phase 2 Clinical Trials

Clinical trials are larger and involve several hundred participants. These studies last anywhere from several months to two years and collect additional information on safety and efficacy. Data gained from phase two trials can be used to determine the composition of the vaccine, how many doses are necessary, and a profile of common reactions.

Phase 3 Clinical Trials

These are the next step, unless the vaccine is ineffective or causes health problems, and are expanded to involve several hundred to several thousand volunteers. Typically, these trials last several years. Because the vaccinated group can be compared to those who have not received the vaccine, researchers are able to identify true reactions.

 

If the clinical trials demonstrate that the vaccine is safe and effective, the manufacturer submits a Biologics License Application (BLA) to FDA requesting two licenses: one for the vaccine (product license), and one for the production plant (establishment license). During the application process, the FDA reviews the clinical trial data and proposed product labeling. In addition, the FDA inspects the plant and goes over manufacturing protocols to ensure vaccines are produced in a safe and consistent manner. Only after the FDA is satisfied that the vaccine is safe is it licensed for use in the general population.

Phase 4 Clinical Trials

Safety monitoring and research begins after a vaccine is licensed and recommended for public use. The Advisory Committee on Immunization Practices (ACIP) continues to monitor vaccine safety and effectiveness data even after the vaccine’s routine use and may change or update recommendations based on that data. Also, FDA requires all manufacturers to submit samples from each vaccine lot prior to its release. Manufacturers must provide the FDA with their test results for vaccine safety, potency, and purity. Each lot must be tested because vaccines are sensitive to environmental factors like temperature, and can be contaminated during production. The FDA rarely has recalled vaccine lots, for concerns such as mislabeling, contamination during production, and potential manufacturing problems at a production plant.

While clinical trials provide important information on vaccine safety, the data are somewhat limited because of the relatively small number (hundreds to thousands) of study participants. Rare side effects and delayed reactions might not be evident until the vaccine is administered to millions of people. Therefore, the federal government established the Vaccine Adverse Event Reporting System (VAERS), a surveillance system to monitor adverse events following vaccination. In addition, large-linked databases containing information on millions of individuals, such as the Vaccine Safety Datalink (VSD), have been created to study rare vaccine adverse events. 

Adapted from the CDC website.