By Sravya Chary
Two COVID-19 vaccine manufacturers recently submitted Emergency Use Authorization (EUA) requests to the Food and Drug Administration (FDA) for their candidates.
While the need for a safe and efficacious COVID-19 vaccine is dire and immediate, an EUA may not be the best regulatory method to provide access. Experts warn that the EUA pathway may impede vital scientific progress needed to establish the long term safety and efficacy of investigational COVID-19 vaccines.
According to the FDA, an Emergency Use Authorization is a tool that allows an unapproved medical product to be released to the public in a health crisis given that the medical product meets statutory criteria outlined in Section 564 of the Federal Food, Drug, and Cosmetic Act.
The statutory criteria are as follows: 1) an emergency must be declared, 2) the agent specified for the declaration of the emergency can cause a serious or life-threatening disease/condition, 3) it is reasonable to believe the medical product is effective in treating, diagnosing, or preventing that disease/condition based on scientific evidence, 4) the known potential benefits outweigh the known potential risks, and 5) there is no adequate, approved, alternate treatment available.
Although the issuance of an EUA is beneficial in that it would allow the public to access a potentially promising vaccine without having to wait through the long FDA approval process, experts have stated concerns regarding the impediment an EUA may pose to accurate assessments of COVID-19 vaccines for safety and efficacy.
In October, the FDA issued a guidance document for vaccine manufacturers with information regarding the data they must provide in order for the agency to issue an EUA.
On November 18, 2020, Pfizer and BioNTech released a statement that following the conclusion of a phase 3 study of their COVID-19 vaccine candidate, in which all primary efficacy endpoints were met, the organization planned to submit an EUA request to the FDA.
BREAKING: We are proud to announce, along with @BioNTech_Group, that the Phase 3 study of our #COVID19 vaccine candidate has met all primary efficacy endpoints.
— Pfizer Inc. (@pfizer) November 18, 2020
Moderna recently followed suit as the second vaccine developer to apply for an EUA.
But experts have expressed concern with issuing an EUA for these COVID-19 vaccines.
David Cyranoski writes in Nature that for vaccine trials, initially participants are blinded, and therefore unaware of whether they receive the vaccine or a placebo. However, following the issuance of an EUA, the company would have an ethical obligation to disclose the vaccine as an option to those trial participants in the placebo arm. This raises scientific concern. If too many individuals in the placebo arm cross over, the control group may not be large enough to be used as a comparator. Statistically significant results may be too difficult to gather, rendering the results ineffective for drawing conclusions on the long term safety and efficacy of the vaccine.
Just weeks prior to receiving requests for EUAs, the FDA has shown signs of “getting cold feet” over the issuance of an EUA for a COVID-19 vaccine.
According to Arnold Monto, acting chair of the FDA’s Vaccines and Related Biological Products Advisory Committee and leading epidemiologist at the University of Michigan’s School of Public Health, vaccine developers may not be able to generate enough data to “successfully apply for a full license” if issued an EUA.
Further Stephanie Schrag, an epidemiologist at the Centers for Disease Control and Prevention (CDC), warns that an EUA may impede the collection of information regarding secondary endpoints, such as whether the vaccine decreases the number of severe COVID-19 cases, and its efficacy in those disproportionately affected (the elderly and people of color).
Another avenue that has been raised as a potential regulatory pathway is expanded access. Expanded access, otherwise known as compassionate use, is a pathway through which a patient can gain access to the investigational vaccine outside of clinical trials. The expanded access route would allow those who are at highest risk to access the investigational vaccine without “opening the floodgates” in the way an EUA would. According to Jesse Goodman, a former FDA scientist, expanded access could ensure the continuation of clinical trials, however, the expanded access process is inefficient and strenuous.
The FDA will meet to evaluate the Pfizer application on December 10 and Moderna’s on December 17. Although an EUA is likely in the cards for at least one of these investigational vaccines, an issuance may eventually prove to be disastrous for our understanding of overall safety and efficacy.
The above opinions are wholly my own and in no way represent the opinions of my associated institutions.
