The FDA’s role in the development of vaccines involves strain selection and reference standard population, lot release, evaluation of safety and efficacy, post-market surveillance, advancing vaccine technology and helping to ensure public confidence. The importance of public confidence in the safety of vaccines is illustrated in the stark difference between the incidence of deaths and other adverse events in people who are vaccinated with a Measles, mumps, rubella (“MMR”) vaccine (3.435 per 10,000) vs those who contract measles (>3000 per 10,000). A similar difference in incidence exists with influenza and flu vaccines.

Most of the SARS-CoV-2 vaccines are targeting the spike protein (S). Some are developing vaccine candidates that target the nucleoprotein (N). Others are targeting both or the whole viral particle. Approaches include DNA, RNA, Protein Subunit, Inactivated Virus, Non-Replicating Viral Vector, Replicating Viral Vector and Virus-like Particles.

At FDA our priorities for the development of SARS-CoV-2 vaccine are manufacturing quality, safety, efficacy and post-market surveillance. In June, we put out guidance for the development of licensure of vaccines to prevent COVID-19. It became clear to us that the first wave of vaccines might be eligible for emergency use authorization so we issued guidance on that in October.

FDA encourages enrollment of diverse populations is all phases of vaccine clinical development including racial and ethnic minorities. Enrollment should include populations of elderly individuals, pregnant women and women of
childbearing potential and children. We were specific in our guidance about targeting a 50% efficacy endpoint with a lower limit of a 95% confidence interval of 30%. There has to be a robust safety evaluation and subject follow up should be long enough to evaluate duration of immune response. Accelerated approval may be considered in the future if an applicant can establish a surrogate endpoint that is reasonably likely to predict clinical benefit. Emergency Use Authorization may be appropriate once studies have demonstrated the safety and effectiveness of the vaccine but before the manufacturer has submitted and/or FDA has completed its formal review.

There are 192-194 SARS-CoV-2 vaccines in development globally. FDA has been highly responsive to sponsors regarding vaccine development plans. We are working with our regulatory counterparts and other stakeholders, including WHO, to promote convergence. There are 5 approved gene therapies in the United States. The number of Initial New Drug (“IND”) applications to FDA is increasing noticeably with over 1,000 active IND’s. MIT NEWDIS estimates that there will be 40-60 new gene therapy product launches by 2030. Availability of high quality manufacturing capacity is currently limiting the development of gene therapy. FDA is collaborating with a variety of stakeholders to develop more streamlined pathways that facilitate the manufacturing of advanced therapies.

Unfortunately, current manufacturing platforms are only commercially viable at patient populations of 100 or more. Animal models may be less than that ideal for modeling individualized therapies outside of the clinical setting. New model systems include organoids and humanized mice. We are exploring how to generate efficacy data in very small populations. Bayesian clinical trial designs might be part of the solution. Public-private partnerships to enable product access to diverse populations through streamlined production may improve product access.