By Daniel R. Lucey M.D., MPH, FIDSA
The only past U.S. Food and Drug Administration Emergency Use Authorization for any vaccine was in January 2005 for the licensed (since 1970) anthrax vaccine to be used in military personnel “for prevention of inhalation anthrax for individuals between 18 and 65 years of age who are deemed by the Department of Defense to be at heightened risk of exposure due to attack with anthrax.” This single FDA EUA for a vaccine was in effect for only one year.
Given that Phase III COVID-19 vaccine trials in the United States began July 27, a wide-reaching public dialogue should also begin as soon as possible in August on what criteria the FDA will use, and what it will mean, if the FDA grants EUA for a COVID-19 vaccine. Failure to engage in such a dialogue now will increase the risk of a lack of trust in the safety, efficacy and acceptability of any such vaccine receiving EUA.
One possible venue for such a public dialogue is the National Academy of Medicine, part of the non-governmental National Academy of Sciences.
Although never for any vaccines, multiple EUAs have been issued by the FDA during epidemics such as pandemic H1N1 influenza 2009-2010, Ebola 2014-2016, Zika 2016, and for COVID-19 in 2020.
If an EUA is authorized by the FDA for a COVID-19 vaccine, one of the most likely eligible initial U.S. populations would be health care personnel, and other frontline and essential workers. The US Centers for Disease Control and Prevention reported on July 30 a still-increasing more than 116,000 infections and 578 deaths among people working in health care settings.
Thus, it is important to act now on the anticipation that in September to October 2020 one or more vaccines against COVID-19 will be considered for the first-ever EUA for a vaccine for civilians. Public dialogue now would increase the perception and understanding of the safety and efficacy, trust and acceptability of a COVID vaccine given EUA before full FDA licensure.
FDA Guidance for Development and Licensure of Vaccines to Prevent COVID-19
Part of the essential material for such a public dialogue on an EUA for a COVID-19 vaccine includes the June 30 FDA guidance (non-finalized) for Industry on COVID-19 Vaccine Development and Licensure.
Vaccine efficacy criteria and brief EUA considerations were included in this document.
Regarding efficacy it states: “To ensure that a widely deployed COVID-19 vaccine is effective, the primary efficacy endpoint point estimate for a placebo-controlled efficacy trial should be at least 50%, and the statistical success criterion should be that the lower bound of the appropriately alpha-adjusted confidence interval around the primary efficacy endpoint point estimate is >30%.”
Regarding the issuance of an EUA, the final page (19) of the text states:
“• An Emergency Use Authorization (EUA) may be issued only after several statutory requirements are met (section 564 of the FD&C Act (21 U.S.C. 360bbb2)) (Ref. 23). Among these requirements is a determination by FDA that the known and potential benefits of a product, when used to diagnose, prevent, or treat serious or life-threatening diseases, outweigh the known and potential risks of the product.
- Issuance of an EUA (Ref. 23) may be appropriate for a COVID-19 vaccine provided the standard for issuing an EUA is met. Issuance of an EUA for a COVID-19 vaccine prior to the completion of large randomized clinical efficacy trials could reduce the ability to demonstrate effectiveness of the investigational vaccine in a clinical disease endpoint efficacy trial to support licensure, and such clinical disease endpoint efficacy trials may be needed to investigate the potential for vaccine-associated ERD. Thus, for a vaccine for which there is adequate manufacturing information, issuance of an EUA 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 of the biologics license application.
- In the case of investigational vaccines being developed for the prevention of COVID-19, any assessment regarding an EUA would be made on a case by case basis considering the target population, the characteristics of the product, the preclinical and human clinical study data on the product, and the totality of the available scientific evidence relevant to the product.”
Daniel Lucey, M.D. MPH, FIDSA, FACP, is an infectious diseases physician and adjunct professor of infectious diseases at Georgetown University Medical Center, a senior scholar at the Georgetown University O’Neil Institute, Anthropology Research Associate, Smithsonian Museum of Natural History and a member of the Infectious Diseases Society of America Global Health Committee.He has served as a volunteer medical responder to outbreaks that included the West Africa Ebola crisis. He has collected information on outbreaks starting in 2001 with cases of anthrax in 2001, and including smallpox vaccination 2002, SARS 2003, H5N1 Flu 2004, MERS in 2013, and Ebola in April, 2014, He has gathered, and updated information on the spread of the coronavirus here since Jan. 6.