Maria K. Shockley, BS

The FDA has authorized the use of 3 COVID-19 vaccines in less than a year after the beginning of the pandemic. How did a new vaccine become available to the public so quickly when FDA approval for vaccines typically takes 10 to 15 years?

The answer is through an emergency use authorization (EUA). This provision of federal law allows the secretary of the Department of Health and Human Services (HHS), upon declaration of an emergency, to authorize the use of a “drug, device, or biological product intended for use in an actual or potential emergency.”

The HHS secretary can declare an emergency upon determining the existence of a public health emergency that “affects, or has a significant potential to affect, national security or the health and security of United States citizens living abroad and that involves . . . a biological agent or a disease or condition that may be attributable to such agent.”

 To help in such an emergency, products which are “not approved, licensed, or cleared for commercial distribution” may be authorized for use.

Typically, a newly developed vaccine undergoes a multiphase process before the FDA approves it for use. This process involves preclinical trials, after which an investigational new drug application is submitted.

 When the agency has accepted the application, the vaccine makes its way through phases 1 to 3 of the clinical trial stage of the approval process.

 Throughout the trial stage, investigators collect information on efficacy and safety.

 Once the clinical trials indicate that a vaccine is effective and safe, the developer submits a biologics license application.

 If the FDA determines that the benefits of the vaccine as shown by the trials outweigh any potential risks, it grants the biologics license and the vaccine can be marketed for use in the general public.

On February 4, 2020, HHS Secretary Alex Azar declared that COVID-19 constituted a public health emergency within the definition of the EUA
and that the emergency justified authorizing the use of biological products for its duration.

 Based on this declaration, the authorized use of vaccines could be granted with only interim phase 3 results available if it could be shown that the vaccines’ benefits outweighed any known or potential risks.

On December 11, 2020, the FDA granted an EUA for the Pfizer-BioNTech COVID-19 Vaccine on the basis that “it is reasonable to believe that the known and potential benefits of [the] vaccine, when used to prevent COVID-19. . .outweigh its known and potential risks.” In addition, “based on the totality of scientific evidence available to FDA, it is reasonable to believe that [the] vaccine may be effective in preventing COVID-19.”

Subsequent EUAs issued for the Janssen COVID-19 Vaccine and Moderna COVID-19 Vaccine were granted on the same basis.

 The issuance of an EUA is not, however, the end of the road for these 3 vaccines.

Because the EUA does not give the vaccines “FDA approval” status but merely authorizes their use for the duration of the emergency, the vaccines must continue to undergo clinical trials as they otherwise would. After completion of these trials, each vaccine developer must submit a biologics license application to the FDA for each product to receive approval status.

What are regulators doing to ensure the efficacy and safety of the COVID-19 vaccines? In addition to requiring the submission of biologics license applications, vaccine manufacturers must ensure their facilities comply with current good manufacturing practices, submit certificates of analysis to the EUA file within 48 hours before the release of each lot, and submit quarterly manufacturing reports to the EUA file.

The CDC has also ensured that the COVID-19 vaccines comply with the “FDA’s rigorous scientific standards for safety, effectiveness, and manufacturing quality needed to support [EUA].”

We have already seen one instance in which the agency’s safeguards for ensuring quality have been effective. A COVID-19 vaccine manufacturing facility in Baltimore, Maryland, responsible for manufacturing 2 of the vaccines conflated the ingredients and contaminated approximately 15 million doses of the Janssen vaccine.

 However, the facility caught the mistake during the quality check,

 offering assurance that, despite the speed with which the vaccine was authorized for use, effective safeguards are in place to ensure quality and safety. 

is a JD candidate at the University of Kentucky J. David Rosenberg College of Law in Lexington.

Joseph L. Fink III, JD, DSC (Hon.), BSPHARM, FAPhA, 

is a professor of pharmacy law and policy and the Kentucky Pharmacists Association Professor of Leadership at the University of Kentucky College of Pharmacy in Lexington.

Emergency Use of Medical Products, 21 USC §360bbb-3a (2014). Accessed May 6, 2021. https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title21-section360bbb-3a&num=0&edition=prelim

Vaccine development – 101. FDA. Updated December 14, 2020. Accessed May 7, 2021. https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/vaccine-development-101

Applications for Biologics Licenses; Procedures for Filing. 21 CFR §601.2. Accessed May 7, 2021. https://www.govinfo.gov/app/details/CFR-2011-title21-vol7/CFR-2011-title21-vol7-sec601-2

Determination of a public health emergency and declaration that circumstances exist justifying authorizations pursuant to section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3. HHS. February 4, 2020. Accessed May 8, 2021. https://www.fda.gov/media/135010/download

Emergency use authorization for vaccines to prevent COVID-19: guidance for industry. FDA. Updated February 22, 2021. Accessed May 8, 2021. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-vaccines-prevent-covid-19

Pfizer-BioNTech COVID-19 Vaccine EUA Letter of Authorization reissued. FDA. May 10, 2021. Accessed May 12, 2021. https://www.fda.gov/media/144412/download

Moderna COVID-19 Vaccine EUA Letter of Authorization. FDA. February 25, 2021. Accessed May 8, 2021. https://www.fda.gov/media/144636/download

Janssen COVID-19 Vaccine EUA Letter of Authorization. February 27, 2021. Accessed May 12, 2021. https://www.fda.gov/media/146303/download

FDA letter to ModernaTX Inc. February 25, 2021. Accessed May 12, 2021. https://www.fda.gov/media/144636/download

FDA letter to Pfizer Inc. May 10, 2021. Accessed May 12, 2021. https://www.fda.gov/media/144412/download

Safety of COVID-19 vaccines. CDC. Updated May 11, 2021. Accessed May 12, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/safety-of-vaccines.html

LaFraniere S, Weiland N. Johnson & Johnson vaccine is delayed by a U.S. factory mixup. The New York Times. March 31, 2021. Accessed May 12, 2021. https:// www.nytimes.com/2021/03/31/world/johnson-and-johnson-vaccine-mixup. html

Articles

FDA approvals of vaccines usually take 10 to 15 years, but the pandemic necessitates emergency action.