The Food and Drug Administration says it will keep a high bar for approving a coronavirus vaccine, issuing guidelines Tuesday that indicate the agency will require evidence from large trials that a shot either prevents COVID-19 or decreases its severity in at least half of all people who are vaccinated. “We will not cut corners in our decisions,” FDA Commissioner Stephen Hahn said in a statement announcing the guidance. There are concerns the agency will be under pressure to approve a vaccine before its proven safe and effective, particularly as the U.S. government is directly involved in efforts to rapidly advance coronavirus vaccine development.The FDA indicated an accelerated approval might be possible, but only once regulators have a better understanding of what kind of immune responses are reasonably likely to predict protection from infection with SARS-CoV-2. Emergency authorization, like Gilead’s antiviral drug remdesivir received, would be considered on a case-by-case basis, the guidelines state.
Approving, or otherwise making available, a vaccine for SARS-CoV-2 will be one of the most consequential decisions the FDA faces during the coronavirus pandemic.
Unlike treatments for coronavirus disease, vaccines cleared for use will be given to healthy people, likely healthcare workers and at-risk individuals first but eventually tens or even hundreds of millions of Americans. Confidence that a vaccine can protect against infection or disease, as well as be given safely, will be critical.
But the FDA will in all likelihood have less information to evaluate than it typically would in reviewing a vaccine — the result of compressing development timelines that typically span many years into just months.
At the same time, the agency will be under immense political and public pressure to give health officials the only tool realistically capable of ending a pandemic that appears to be dramatically worsening in the U.S.
The guidelines released Tuesday set out the standards the FDA plans to uphold.
“[M]ake no mistake: the FDA will only approve or make available a COVID-19 vaccine if we determine that it meets the high standards that people have come to expect of the agency,” said Peter Marks, head of the FDA center that will be tasked with reviewing coronavirus vaccines, in a statement.
The guidance instructs vaccine developers to design clinical trial programs extensive enough to support a traditional approval, including late-stage trials testing an experimental candidate in “many thousands of participants.”
Specifically, the FDA said developers could either test whether their vaccines protect against SARS-CoV-2 infection, or COVID-19 disease. In either case, the prospective vaccine should be compared against placebo.
The guidance also suggests the agency would like safety outcomes data for at least 3,000 people inoculated with the vaccine dose intended for use, including adverse event assessments through at least six months following vaccination.
Of particular note are the FDA’s instructions around so-called surrogate endpoints, such as immune response data. For instance, vaccine developers Moderna and CanSino Biologics have reported early data on the levels of neutralizing antibodies their shots produce in healthy volunteers, a marker suggestive of potential protection. (Both are conducting larger studies designed to prove protection, too.)
Currently, however, the FDA isn’t confident such data can stand-in for measuring protection.
“There are currently no accepted surrogate endpoints that are reasonably likely to predict clinical benefit of a COVID-19 vaccine,” the guidance states.
Accelerated approvals based on surrogate endpoints could be possible in the future, the FDA said, but only if more is known about COVID-19 immunology. Immune markers, however, would only be applicable to vaccines of the same type.
A dozen and a half vaccines are now in human testing and the first late-stage studies could begin in July, likely enrolling tens of thousands of people. Some drugmakers, including Moderna and Pfizer, have indicated emergency availability for their vaccines might be possible by this fall — a timeline that’s never before been accomplished in vaccine development.
Even the U.S. government’s goal of making vaccines available to Americans by January 2021 is exceedingly ambitious.
The most likely route for a vaccine to meet those timelines is through an emergency authorization, which the FDA can grant during public health emergencies.