COVID-19 Vaccines: BIO Pushes For EUA Guidance, While HHS’ Azar Downplays Its Importance

US Food and Drug Administration guidance on emergency use authorization for COVID-19 vaccines should be publicly released to provide regulatory clarity to scientists and researchers and strengthen public confidence in any vaccine authorized by the agency, the Biotechnology Innovation Organization says.

“All new FDA guidance should be finalized and communicated with those on the frontlines developing potential vaccines,” BIO president and CEO Michelle McMurry-Heath said in a 1 October letter to Health and Human Services secretary Alex Azar. “Just as importantly, it must also be shared more broadly with the American public.”

However, Azar told lawmakers 2 October that the outcry that has resulted from the guidance’s delayed release equates to making “a mountain out of molehill” because vaccine developers already know what data the agency expects to support an EUA.

COVID-19 vaccines are expected to initially reach the US market under the EUA process. FDA officials repeatedly have said the clinical data package needed for an EUA will closely resemble that for a full biologics license application, although the EUA offers a quicker route for both submission and FDA review. (Also see "COVID-19 Vaccines: EUA Route Offers Advantage In Review Speed, Not Level Of Evidence" - Pink Sheet, 30 Jul, 2020.)

In late June, the FDA released guidance with recommendations on data needed to facilitate clinical development and licensure of COVID-19 vaccines. The agency subsequently announced plans to issue separate guidance on the data and information that would support an EUA. (Also see "US FDA Expects COVID-19 Vaccines To Meet ‘EUA Plus’ Standards, Marks Says" - Pink Sheet, 10 Sep, 2020.)

Among the expected recommendations was the agency’s publicly announced preference for a median of two months of safety follow-up, a timeframe derived from the adverse event experience with other vaccines. (Also see "US FDA’s Two-Month Safety Window For COVID Vaccines Based On Adverse Events In Other Products" - Pink Sheet, 28 Sep, 2020.)

However, President Trump pushed back against the agency’s plans to issue the EUA guidance with the two-month follow-up recommendation, suggesting it was an attempt to slow down the process of getting a vaccine to market. Trump said the White House could block the guidance’s release. (Also see "Hahn Says COVID Vaccine Review Could Take Months As Trump Floats Rejecting New EUA Guidance" - Pink Sheet, 23 Sep, 2020.)

Trump, who repeatedly has said a vaccine could be available by the 3 November presidential elections, announced he had tested positive for COVID-19 on 2 October.

The EUA guidance has yet to be released, and its delay has renewed charges from Democratic lawmakers and public health experts of political interference in the FDA’s work to combat the pandemic.

Center for Biologics Evaluation and Research director Peter Marks recently said the guidance was primarily intended to make the FDA’s evidentiary requirements for an EUA transparent to the general public, and that the companies developing vaccines already are aware of the data the agency expects to see with an EUA request. (See sidebar.)

BIO Urges Release For Scientific, Transparency Reasons

In the letter to Azar, McMurry-Heath asserts the guidance’s publication would be important to vaccine researchers as well as the general public.

The letter notes that more than 180 experimental vaccines for COVID-19 currently are in development, including 10 in Phase III clinical trials.

Four vaccines that have backing from the federal government's Operation Warp Speed program are in Phase III trials in the US, although the US trial for AstraZeneca PLC’s candidate remains on clinical hold due to safety reasons.

“Insight into FDA’s views on clinical and scientific factors underlying emergency use authorization of COVID-19 vaccines would support ongoing research and development.” – BIO’s Michelle McMurry-Heath

“Our organization and member companies are working closely with FDA scientists and public health experts to achieve our shared commitment to testing and developing vaccines in strict accordance with sound scientific principles and with high ethical and safety standards,” BIO’s letter states.

“That is why we were encouraged to learn the FDA has been finalizing new guidance to clarify what biopharmaceutical companies will need to demonstrate for safety and efficacy data in order to receive emergency use authorization for COVID-19 vaccines. Insight into FDA’s views on clinical and scientific factors underlying emergency use authorization of COVID-19 vaccines would support ongoing research and development.”

A lack of transparency also could undermine the public’s confidence in the vaccine development process, the letter states.

“The public must have full faith in the scientific process and the rigor of FDA’s regulatory oversight if we are to end the pandemic. Releasing any additional guidance on granting emergency use authorization for a vaccine will go a long way in accomplishing this critical goal.”

Azar Says Controversy Overblown

In testimony before the House Select Subcommittee on the Coronavirus Crisis, Azar downplayed the importance of the unreleased guidance and suggested the controversy was overblown.

The FDA already has sent letters to vaccine manufacturers explaining what data the agency expects would support an EUA, Azar said, adding that the new guidance the agency proposed to issue was consistent with these letters.

“The FDA has already told the manufacturers what they’re going to look for, and that is what it is.” – HHS’ Alex Azar

Azar acknowledged that the guidance must go through review by White House Office of Management and Budget before it is publicly released.

“I think this is a mountain out of a molehill,” Azar said. “The FDA has already told the manufacturers what they’re going to look for, and that is what it is.”

Azar also countered Democratic lawmakers’ assertions of political interference in various efforts by the country’s public health agencies to combat the pandemic, and he vowed that any decision on a vaccine would be made by FDA scientists.

By statute, the HHS secretary holds the legal authority to approve or reject a drug or biologic application. That authority generally is delegated to the FDA, although there is precedent for an HHS secretary to overrule the agency’s scientific experts. (Also see "A Matter Of Precedent: US FDA Sometimes Labors Under Weight Of Unpopular Or Unfavorable Decisions" - Pink Sheet, 14 Sep, 2020.)

“We have many people who bring a lot of expertise and knowledge to the table,” Azar said, explaining that debate is encouraged. “Those people can participate. Those people can contribute. They can challenge. They can ensure good decisions are made.”

“What I’m telling you is at the end of the day, it will be FDA career scientists,” Azar said. “Dr. Peter Marks is going to make the decision whether a vaccine is safe and effective.”