Army Spc. Angel Laureano holds a vial of the COVID-19 vaccine, Walter Reed National Military Medical Center, Bethesda, Md., Dec. 14, 2020. (Courtesy of Wikimedia Commons)

On November 2, the Pfizer-BioNTech COVID-19 vaccine was approved for administration in an age-appropriate dosage for children aged 5-11. With this recent milestone, many of us have been wondering what the vaccine development and approval processes entail. Here we’ll dive into a brief, general overview of the stages. 

The vaccine development cycle includes an exploratory stage, a pre-clinical stage, clinical development, regulatory review and approval, manufacturing, and quality control. Clinical development contains three phases, the first of which consists of small groups receiving a trial vaccine. Next, the clinical study expands and the vaccine is distributed to people sharing characteristics found in the intended vaccine population (e.g. age, physical condition). In Phase III, the vaccine is administered to thousands of people and tested for efficacy. Usually, there is an additional Phase IV consisting of ongoing studies after the vaccine has been approved and licensed. 

The U.S. Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research (CBER) regulates all vaccine products within the U.S. Vaccine sponsors must follow a comprehensive approval process, which includes an Investigational New Drug application, pre-licensure vaccine trials, a Biologics License Application, inspection of the manufacturing facility, a presentation of findings to the FDA’s Vaccines and Related Biological Products Advisory Committee, and product labeling tests. If a formal approval is granted, the FDA continues to monitor production activities through periodic facility inspections and safety testing in each vaccine lot. The Vaccine Adverse Event Reporting System analyzes information from reports of side effects from U.S.-licensed vaccines. 

In an effort to vaccinate populations as soon as possible, Pfizer-BioNTech, Moderna and Johnson & Johnson’s Janssen vaccines were all issued Emergency Use Authorization (EUA) in December 2020. Under an EUA the FDA may allow the distribution of unapproved medical products to prevent, diagnose or treat disease when alternatives are lacking. 

Once a manufacturer submits an EUA request, the FDA must determine that the known and potential benefits outweigh the known and potential risks of the vaccine. COVID-19 vaccine EUA requests are submitted to the FDA based on Phase III trial analysis or interim analysis — analysis before the end of a trial once data has met the predetermined success mark. The EUA submission must include all safety data from Phases I and II, and Phase III data must show that at least half of fully-vaccinated participants receive at least two months of follow-up reporting. Within the Phase III safety database, over 3,000 fully-vaccinated participants must be followed for serious side effects for at least one month.

A version of this article appeared on p.13 of the November 18, 2021 print edition of the Daily Nexus.