An expert panel of the US Food and Drug Administration will be offering advice on the appropriateness of an emergency use authorization of a COVID-19 vaccine and the safety and effectiveness data needed for approval before the agency has received an application.
FDA announced that the Vaccines and Related Biologics advisory committee will convene on 22 October to “discuss, in general, the development, authorization and/or licensure of vaccines to prevent COVID-19,” and that no specific application will be discussed.
Advisory committee members confirmed earlier this month that a meeting was scheduled for that date. (Also see "Warp Speed Lives Up To Its Name: FDA Planning Late October Vaccine Advisory Committee" - Pink Sheet, 4 Aug, 2020.)
FDA’s announcement, to be published in the Federal Register on 28 August, shows the agency is preparing for review of applications, which may be submitted before the end of the year or early next year after two candidates entered Phase III trials in the US in July. The agency’s decision to have a more general meeting also raises questions about whether the FDA will bring every coronavirus vaccine application before an advisory committee.
Stakeholders are encouraged that the meeting is being held in advance of an application.
“I think it’s really helpful for the staff to gather information from experts on the approach they are considering for vaccines,” said Luciana Borio, former FDA acting chief scientist.
“Given the desire to expedite authorization for these products, FDA will have to balance very carefully the data required before authorization and the data required after authorization,” she added. Advisory committee members “can help delineate what is necessary” to do before and after deploying a vaccine.
Borio said it is not known yet whether the committee will review every vaccine application. She said the public would welcome the news that FDA relied on the committee to make recommendations about the supply of a vaccine. And “given the recent missteps by FDA,” she said, alluding to the emergency use authorizations for hydrochloroquine and convalescent plasma, “it might be necessary to get input” before deploying a vaccine which will be used broadly by the public.
Opposing Views On EUAs
Borio has been critical of the emergency use authorization (EUA) for convalescent plasma, which generated widespread concern that it might undermine public trust in COVID-19 vaccines. (Also see "Plasma Authorization Raises Fears Of Politically-Influenced COVID-19 Vaccine Decisions, Compromised FDA" - Pink Sheet, 24 Aug, 2020.)
But Borio thinks an EUA for a COVID-19 vaccine may be appropriate. “For this vaccine, it may be reasonable to consider an emergency use authorization for a certain segment of the population after randomized trials” indicate safety and effectiveness but the vaccine is not yet approvable, she stated.
For full approval, manufacturing issues could be a hold-up that wouldn’t necessarily impact the clinical value of the vaccine, Borio suggested. A key component of licensing is commercial scale manufacturing and its specifications must be delineated before approval. In the case of COVID-19 vaccines, she said the facilities being used to manufacture them are not necessarily the usual facilities companies have used or the ones that will continue to manufacture the vaccines.
Sidney Wolfe, founder and senior adviser of Public Citizen’s Health Research Group, said the advisory committee will be valuable in providing FDA input from those opposing an EUA for a COVID-19 vaccine. Although the Federal Register notice does not specify “emergency use authorization” as a discussion topic, Wolfe said its listing of “authorization” was a shortcut for EUA.
“The FDA in some way other then internally or in consultation with HHS needs to get clear in their mind the argument against having an EUA,” he said.
Wolfe, who will be speaking at the public hearing session of the meeting, sent a 6 August letter to HHS Secretary Alex Azar, FDA Commissioner Stephen Hahn, Center for Biologics Evaluation and Research Director Peter Marks, and National Institute of Allergy and Infectious Diseases Director Anthony Fauci, urging them to end any consideration of issuing EUAs for COVID-19 vaccines.
The letter notes that FDA has never issued an EUA for a vaccine, except for an anthrax vaccine in response to the purported threat of biological warfare.
“The ‘logic’ of saving several months by a faster but riskier EUA pathway will surely be outweighed by the loss in public confidence in the vaccine, accompanied by decreased willingness to be vaccinated,” the letter states.
Several formal FDA officials have also expressed hesitancy about an EUA for a COVID vaccine, but feel it could be appropriate in some circumstances. (Also see "COVID-19 Vaccines: Ex-FDA Leaders Urge High Bar For Emergency Use Authorization" - Pink Sheet, 5 Apr, 2020.)
Will Sponsors Present Data?
There is precedent for FDA seeking panel input on a vaccine before an application was submitted. In 2009, the vaccines advisory committee gave the agency advice on whether it was correctly approaching the licensure of adjuvanted H1N1 influenza vaccines but did not give any recommendation on whether or not to approve them. (Also see "Adjuvanted H1N1 Vaccine Excites FDA Panel, But Jury Is Still Out" - Pink Sheet, 23 Jul, 2009.)
However, that situation was far different as the vaccine for the H1N1 pandemic involved a change in the strain of influenza vaccine rather than new technology for a novel coronavirus.
It is unclear whether sponsors will be presenting current data on their vaccine candidates. Hahn said in a 26 August tweet about the committee’s discussion that “the public will be able to see the data that we have been asked to evaluate.”
Asked if it would be presenting data, Pfizer Inc. said only, “We view this as an important milestone in FDA’s data-driven, scientific review process that promotes public confidence in the safety, efficacy, and quality of COVID-19 vaccines.”
Moderna, Inc. did not respond to a query, and Sanofi Pasteur said it would be monitoring the meeting. Moderna and Pfizer both made presentations on the clinical development of their candidate vaccines at the 26 August meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP). (Also see "Who’s No. 2? After Health Care Workers, A Hot Debate Over Next Group To Get COVID Vaccine" - Pink Sheet, 26 Aug, 2020.)
Moderna and Pfizer/BioNTech SE are the furthest along in developing a COVID-19 vaccine in the US, as both began Phase III trials of their candidates on 27 July. AstraZeneca PLC and Oxford University are in Phase III trials in the United Kingdom, Brazil, and South Africa and are expected to enter Phase III trials in the US this month.
Next in line, Johnson & Johnson’s Janssen unit is scheduled to begin a Phase III trial of its candidate in mid-September and Novavax, Inc. will begin a Phase III trial of its candidate at the end of September. Sanofi/GlaxoSmithKline plc are expected to commence a Phase I trial of their candidate vaccine in early September. (Also see "AstraZeneca, Janssen, Novavax Likely To Be Next ‘Warp Speed’ Vaccines In Phase III" - Pink Sheet, 3 Aug, 2020.)
Operation Warp Speed Chief Adviser Moncef Slaoui and Matthew Hepburn, program manager at the Department of Defense’s Defense Advanced Research Projects Agency, gave an update on the status of vaccine candidates in a 26 August perspective piece in the New England Journal of Medicine. They noted that Operation Warp Speed is providing financial and technical support to eight vaccines, six of which have been announced: those of Moderna, Pfizer/BioNTech, AstraZeneca, Janssen, Novavax, and Sanofi/GSK.
Slaoui and Hepburn noted that to permit appropriate comparisons among vaccine candidates and to optimize vaccine utilization after approval by the FDA, the Phase III trial endpoints and assay readouts have been harmonized through a collaborative effort involving the NIAID, the Coronavirus Prevention Network, Operation Warp Speed, and the sponsor companies. (Also see "'Warp Speed’ Vaccine Trial Network Aims For Both Harmony And Velocity" - Pink Sheet, 12 Aug, 2020.)
Operation Warp Speed, a partnership of the Department of Health and Human Services, the Department of Defense and the private sector, was launched in May with the goal of delivering tens of millions of doses of a SARS-CoV-2 vaccine approved or authorized by FDA for use in the US population by the end of 2020 and to have as many as 300 million doses available and deployed by mid-2021.
Vice President Pence believes this goal will be met. In a 26 August speech at the Republican National Convention he declared: “I’m proud to report that we’re on track to have the world’s first safe, effective coronavirus vaccine by the end of this year.”
But many believe that data for approval won’t be available by then, so the goal may be issuance of an EUA.
Wolfe said that if a vaccine were set to be approved by the end of the year that would be the topic of the advisory committee meeting. He said that for issuance of an EUA, a vaccine would have to meet statistical endpoints, and “I don’t see how you can get that before trials are done.”