Editor's Note: On Tuesday afternoon, the Food and Drug Administration issued formal guidelines for emergency authorization of a coronavirus vaccine, just hours after revealing the criteria in another document and one day after the White House reportedly blocked the guidelines release.
- The Food and Drug Administration on Tuesday appeared to sidestep objections reportedly raised by the White House to stricter standards for an early coronavirus vaccine approval, publishing criteria the agency had previously communicated to drugmakers on the requirements for any emergency authorization.
- The disclosed requirements are not part of formal agency guidelines, which The New York Times reported Monday had been blocked by White House officials, but rather were included in preparatory materials for an advisory panel meeting on coronavirus vaccines that's scheduled to be held later this month.
- The criteria spelled out in the newly published document, if adhered to closely by the FDA, would make an emergency vaccine authorization before the Nov. 3 presidential election less likely. Most notably, the agency has asked drugmakers to submit a median of two months of follow-up from study participants in late-stage clinical trials.
The Trump administration has staked a lot to the speedy delivery of a coronavirus vaccine, pledging more than $10 billion to half a dozen drugmakers advancing experimental shots. Operation Warp Speed, the administration's vaccine project, has promised tens of millions of doses will be available before the end of this year and hundreds of millions by the middle of 2021.
President Donald Trump, however, has repeatedly called for even more ambitious timelines, suggesting a vaccine could come sooner, perhaps before next month's election. His statements have ramped up pressure on the FDA and made the agency's planned requirements for an early approval the subject of a political battle between White House officials and regulators.
On Monday evening, The New York Times and POLITICO both reported the White House had blocked the release of the FDA's guidelines, which Trump last month claimed without basis were politically motivated.
The document posted Tuesday reveals the FDA already informed drugmakers of its standards for an emergency authorization and, by detailing what was communicated, accomplishes much of what the agency sought to do by releasing additional guidelines. Discussion of approval standards is typical between the FDA and drugmakers, even without the issuance of formal guidance.
The FDA previously set out standards for a full approval of a coronavirus shot back in June, indicating clinical trial results would need to show a vaccine to be at least 50% effective in preventing COVID-19 or infection with SARS-CoV-2.
Emergency use authorizations, or EUAs, usually require less evidence, although FDA officials have indicated a vaccine authorization would be more like an "EUA plus," given the potential for widespread use among healthy people.
According to the new document, the FDA will still require proof an experimental vaccine is at least 50% effective for an emergency authorization. Additionally, the agency wants a median of two months of data from clinical trial participants following completion of vaccination, which for the leading candidates consists of two shots spaced three to four weeks apart.
At least five cases of severe COVID-19 would need to be observed in the participants who have received a placebo, the FDA told drugmakers, in order to determine the risk of respiratory disease induced by vaccination — a key safety worry for both developers and regulators.
These criteria were previously reported by The Washington Post and The Wall Street Journal, but weren't confirmed by the FDA.
In the U.S., vaccines developed by Pfizer, Moderna and AstraZeneca are the most advanced in testing, each having begun Phase 3 trials that are enrolling tens of thousands of participants. Moderna's chief executive, however, has said initial data aren't likely until late November, and AstraZeneca's study is currently on hold due to safety concerns raised by a case of neurological illness in a U.K.-based study.
Pfizer, then, is the only developer with a chance to disclose data and ask the FDA for an EUA before Nov. 3. The company has enrolled 36,576 people into its principal study, and some 28,000 have since received their second shot.
Trial plans made public by Pfizer last month show the independent committee overseeing the study can look at interim data four times — after 32, 62, 92 and 120 COVID-19 cases have been reported — with a primary analysis to follow at 164 cases.
Albert Bourla, Pfizer's CEO, has said results from one of those early interim looks could come by late October. But it's unlikely that the drugmaker would have a median of two months of follow-up from all the individuals who have been dosed twice by that point.
Additionally, an EUA would take the FDA "weeks" to go over, according to Peter Marks, head of the FDA division responsible for vaccine reviews.
Marks, speaking Monday to JAMA editor Howard Bauchner in a webcast interview, noted, however, that the agency could be flexible on that two month standard.
"If it turns out the median is 7 weeks and not two months, that's not going to be an issue," he said.
Still, with only 28 days before the election, Pfizer would need to disclose data and have submitted an EUA request to the FDA by next week at the latest for a pre-election approval to be possible.
The document released Tuesday also notes the FDA asked developers to submit their manufacturing information "not less than one month" prior to an EUA application, meaning Pfizer would have needed to already share that data with regulators.
In an emailed statement, Pfizer said it "will support and meet or exceed the standards for safety, efficacy, and manufacturing that the agency adopts." Moderna did not return BioPharma Dive's request for comment by publication.
The FDA acknowledged in an email to BioPharma Dive the information contained in the document released Tuesday, but did not elaborate on whether it would stand in place of formal guidance.
Editor's note: This article has been updated with comment from Pfizer.