An Overview Of Vaccine Development, Approval, And Regulation, With Implications For COVID-19.

Kesselheim, Aaron S; Darrow, Jonathan J; Kulldorff, Martin; Brown, Beatrice L; Mitra-Majumdar, Mayookha; Lee, ChangWon Charlie; Moneer, Osman; Avorn, Jerry

The Food and Drug Administration generally approves vaccines when their benefits outweigh their risks for their intended use. In this paper, we review current and potential approaches to this critical role of the FDA. The FDA has established pathways to accelerate vaccine availability prior to approval, such as emergency use authorization, and to channel resources to high-priority products and allow more flexibility in the evidence required for approval, including accelerated approval based on surrogate markers of effectiveness. Among the 35 new vaccines approved in the US from 2006-2020, about two-thirds of their pivotal trials used the surrogate outcome of immune system response, and just one-third evaluated actual disease incidence. Post-approval safety surveillance of new vaccines-particularly vaccines receiving expedited approval-is crucial. Currently this is accomplished through such mechanisms as the Centers for Disease Control and Prevention/FDA Vaccine Adverse Event Reporting System, the CDC Vaccine Safety Datalink, and the CDC Clinical Immunization Safety Assessment Project. Adverse events detected in this way may lead to changes in a vaccine's recommended use or its withdrawal from the market. Regulatory oversight of new vaccines will have to balance speed with rigor and decisiveness to effectively address the coronavirus disease 2019 (COVID-19) pandemic. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].