Industry Backs Clear FDA Standards for COVID Vaccine Authorization

After a highly publicized dispute over FDA requirements for authorizing a vaccine to protect individuals from COVID-19, the agency was able to publish updated requirements for vetting and approving an Emergency Use Authorization (EUA) for new coronavirus preventives. In spelling out the data expected for such authorization, agency officials emphasized the importance of fully vetting the safety and efficacy of any new coronavirus vaccine through a highly transparent process to boost public confidence in the ability of vaccines to save lives. This review process, though, makes it unlikely that any vaccine currently in late-stage testing will be fully vetted and available to patients before mid-November, and more likely early next year.

FDA published its guidance Oct. 6, 2020 following several weeks of delay due to administration opposition. The guidance spells out FDA’s standards for issuing an EUA, including median follow-up data for at least two months after vaccination of Phase III clinical trial participants, safety data on over 3000 vaccine recipients, plus reports on a total of five or more severe COVID-19 cases in the placebo group to address concerns about possible vaccine-induced respiratory disease.

FDA submitted the proposed guidance to the White House budget office in late September, only to meet objections from President Trump that it was “a political move more than anything else” to delay public access to a vaccine before the election. The President later stated that vaccine makers also opposed FDA’s stricter standards, but industry leaders rejected this claim. Pfizer CEO Albert Bourla stated that his company had not discussed vaccine guidelines with the White House, as that would undermine FDA’s independence. The Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Innovation Organization (BIO) further backed FDA’s clarifying guidance and transparency in the vaccine review process. And Moncef Slaoui, leader of the White House’s Operation Warp Speed initiative, added support for FDA’s plan to request adequate safety information.

Countering vaccine hesitancy

Through the debate, officials in the Center for Biologics Evaluation and Research (CBER) emphasized that the EUA safety data requirement was already well known to vaccine manufacturers and that one aim was to assure manufacturers that FDA would hold all vaccine development programs to the same standards. CBER director Peter Marks further emphasized that the guidance sought to reassure the public that granting an EUA would not be a rushed decision on vaccine safety and efficacy to meet political goals, and that a vaccine EUA would require more data than for the more usual emergency authorizations for therapeutics and other medical products.

The release of the actual EUA guidance was almost anti-climatic, as CBER had provided most of the specifics the day before as background material for upcoming deliberations by the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting scheduled for Oct. 22, 2020. That session will discuss overall data requirements, which will be applied to all vaccine applications and be scrutinized publicly by this expert panel before any product is approved for broader patient use.

In several recent presentations, Marks explained the cost-benefit reasoning for authorizing faster, emergency-use of COVID vaccines, as opposed to requiring the more extensive data needed to file a Biologics License Application (BLA) usually required for vaccines. While the longer process is the gold standard for FDA vaccine approval, Marks noted at a meeting sponsored by the Friends of Cancer Research in late September that COVID vaccine trials will obtain sufficient data on safety and efficacy, as spelled out in guidance issued in July, but will not “require the bar to be so high as to cost lives.” The data in an EUA has to come from a well-designed Phase III trial that provides compelling information on efficacy, permitting the regulators to move forward without all the “bells and whistles” FDA normally requires. And authorities will be able to detect later safety signals due to the more advanced public health surveillance systems that were not established in the 1970s for the swine flu epidemic.

In an online interview with the Journal of the American Medical Association (JAMA), Marks described more fully the vaccine review and approval process, noting that even though the data in an EUA is stripped down from a BLA, it still can run to thousands of pages of line and tabular listings. An EUA review could take several weeks, as opposed to many months for a BLA, as there may be less extensive discussion between FDA and the EUA sponsor, but the submission will contain much of the same information on clinical studies and manufacturing. And with an accelerated review process, FDA will want to see a safety profile that is “incredibly clean,” Marks emphasized, for a vaccine to be used by millions of people.

In discussing CBER priorities at the annual meeting of the Food and Drug Law Institute (FDLI) this week, Marks explained that requesting clinical trial safety data for two months after final vaccine administration should provide enough time to capture most adverse events, while not extending the research so long as to delay access to a vaccine that can save lives. Most adverse events of concern show up within a six-weeks to two-months period after vaccination, justifying the two-months follow-up period.

After examining the first few vaccines, Marks anticipates that FDA will get a better sense of how well different products generate immune response vs. clinical response, which could greatly speed up the development process. But as these initial vaccines may have different effects on different populations, a highly transparent review process can help the public understand the pros and cons and decide which vaccine they want.

About the author

Jill Wechsler is Pharmaceutical Technology's Washington Editor, jillwechsler7@gmail.com.