The authorized or approved vaccines were initially tested in animals and early phase clinical trials, in which scientists evaluated different doses, checked for the expected immune responses and monitored for potential safety issues. To find out whether the shots prevent disease and are safe, the vaccines that passed the first set of tests were then evaluated in phase 3 trials.
The Moderna and Novavax phase 3 trials each included about 30,000 volunteers, while the Pfizer/BioNTech and Johnson & Johnson trials included about 44,000 each. In each of these trials, half of the participants received a placebo, while the other half received the vaccine, and the volunteers were followed over time to see if they fell ill with COVID-19 and had any adverse reactions.
The trials were overseen by independent data and safety monitoring boards, and the results were reviewed not only by the Food and Drug Administration, which made the decision to authorize the vaccines for emergency use, but also by an outside panel of experts advising the agency. Another independent group, the CDC’s Advisory Committee on Immunization Practices, also reviewed the data and recommended use of the vaccines.
Following analysis of additional data from the phase 3 clinical trials, safety surveillance data and a review of the manufacturing process, including inspections of production facilities, the FDA granted full approval of the Pfizer/BioNTech vaccine on Aug. 23, 2021, and the Moderna vaccine on Jan. 31, 2022.
Pediatric versions of the mRNA vaccines were authorized based on immune response data, which showed vaccinated kids had similar immune responses to vaccinated young adults, for whom a clinical trial previously demonstrated efficacy. Booster doses of the original vaccines were also authorized primarily based on data showing the additional shots increased levels of virus-specific antibodies.
For the Pfizer/BioNTech and Moderna bivalent booster shots, which target both the original version of the coronavirus and omicron subvariants, the FDA used an approach similar to how it approves flu vaccines each year, in which clinical studies are not required since the changes to the vaccine are minor. Regulators considered animal data, along with clinical data on another omicron bivalent booster and data on the original shots.
Human trials for the omicron-updated bivalent boosters are ongoing.