The Process of Vaccine Development
During the course of development of a vaccine, it undergoes rigorous preclinical studies to help identify the correct dose and make sure that it is safe for testing in people. Once these studies are completed, and prior to testing in humans, the vaccine developer submits an investigational new drug application (IND) to the FDA for their review. The FDA reviews both the preclinical studies and the plans for human testing to assure that the plans are sound and that it is safe to proceed or whether additional preclinical testing needs to be done, or if the testing plans in humans need to be changed.
Once the FDA has granted IND approval, the development of a vaccine will continue through three sequential phases of clinical trials described further below.
The investigational vaccine is given to 20 to 100 healthy, adult volunteers to determine if it is safe and tolerable to the participant, generates a response which indicates that it may protect the individual from disease, and to determine the proper dosage. Phase 1 DVTU vaccine studies have included studies of a Yellow Fever virus vaccine candidate, a West Nile virus vaccine candidate, and an adjuvanted influenza A H5N1 vaccine candidate.
The investigational vaccine is given to several hundred volunteers in the population for whom the vaccine is intended (e.g. children, pregnant women, or older adults) to further assess its safety, protective response, and define the optimal dose and vaccination schedule. Phase 2 DVTU vaccine studies have included studies of the 2009 H1N1 pandemic influenza vaccines in adults, children, and pregnant women. Studies of adjuvanted influenza A H7N9 influenza vaccine included adults and older adults.
The investigational vaccine is given to thousands of volunteers in the population for which the vaccine is intended. The aim is to determine the vaccine’s safety and efficacy in preventing the disease for which it was developed compared with the occurrence of the same disease in a group of participants who do not receive the vaccine. In these studies, participants are often randomly assigned to either receive the vaccine being tested or a matching substance, called a placebo, that does not contain the vaccine. Phase 3 DVTU vaccine studies have included studies of COVID-19 vaccines and studies of rotavirus vaccine.
Before a Vaccine Trial Starts
Before a trial starts, it must also receive approval from an Institutional Review Board (IRB) to further assure that the rights and welfare of human subjects are being protected. Trial progress is reported to both the FDA and IRB on a regular basis or on an immediate basis if any safety concerns are noted. A Data Safety Monitoring Board (DSMB) or Safety Monitoring Committee (SMC) may also be required to review trial data at regular intervals to further monitor study participant safety. Therefore, there are many groups involved in the review of study data to assure study participant safety.
Vaccine Trial Approval Process
Upon completion of human testing, the vaccine developer will submit a biologic license application to the FDA. The application will describe both the preclinical and clinical trial results. The FDA will also review the manufacturing processes for the vaccine and make a determination as to whether a vaccine is both safe and effective prior to issuing an approval for use. Under certain circumstances when there is an emergent public health need, the FDA may issue an Emergency Use Authorization (EUA) for a vaccine prior to issuing a full approval. An EUA was issued for several of the COVID-19 vaccines tested during the recent COVID-19 pandemic.
After a Vaccine is Approved
Following approval, vaccines may undergo additional testing to continue to both monitor vaccine safety and further assess their best use. The FDA will sometimes request that additional studies be performed as a condition for their approval. These studies are sometimes called Phase 4 studies. DVTU is also a site for the CDC-sponsored Clinical Immunization Safety Assessment (CISA) project that assesses vaccine safety questions after vaccines are approved for use.
More info: CDC's Vaccine Testing and Approval Process