FDA center directors on lessons from the EUA pathway: Flexibility serves us well
The flexibility of emergency use authorizations, and allowing the FDA to accept more uncertainty during the pandemic so far, has ultimately aided its response to Covid-19, center directors said Tuesday at a workshop at the National Academies of Sciences, Engineering and Medicine.
Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, pointed to the agility of the EUAs, and the ability to quickly revoke any EUAs, as well as the transparency around those decisions as to what led to the evolution of the types of therapeutics that have been authorized (see chart below).
“Agility is very important, and the EUA allows us that,” she said, stressing the ability to revoke EUAs very quickly and saying FDA wishes it had that ability, when the data warranted, outside of the pandemic.
“The big takeaway for me, based on the past several months, is the importance of collaboration across the US government agencies and with international counterparts and the research community,” Cavazzoni said. “The other important takeaway is having a regulatory framework that allows us to be agile and flexible.”
It’s important for the public to understand the evidence and data generation continues even after an EUA, Cavazzoni said, offering the example of hydroxychloroquine, which had its EUA revoked:
What has been lost in this discussion is that authorization was incredibly narrow and the fact sheet specifically said it should be limited to patients who could not be in clinical trials. Almost immediately after these trials read out, the EUA was revoked. Despite that, there was so much noise around this and it’s part of our lessons learned on communicating facts.
With the authorized monoclonal antibodies for Covid-19, Cavazzoni noted that it was clear these could save lives but “what we saw was very slow uptake last fall and into the spring until this summer where finally the message went through and now we have limited supplies. We need to work together more effectively to break through the noise.”
Josh Sharfstein, a Johns Hopkins professor who was once considered for the top FDA commissioner position, also questioned the center directors earlier on Tuesday on how industry often leads the conversation around the data on new Covid-related therapeutics and vaccines.
Cavazzoni said her center is “constrained by laws and regulations on what we communicate” and from its perspective, “we would welcome broader authorities when it comes to communication about the programs, not only on issuance of EUAs and education, as well as EUAs that end up being declined. I think this is an area prime for further thinking.”
Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, added that he’s hesitant to call for any major changes to the EUA pathway. “It’s not that usual that I think of a particular statutory authority as incredibly well crafted but our emergency use authorization is crafted quite well to deal with a range of things that can come our way and it’s up to us to ensure it’s used properly, not to mess around with the statute.”
“If we’re thinking about anything in this area, it’s minor redecoration, not renovation,” he said. Earlier in the panel discussion Marks mentioned the idea of potentially combining the efforts of the FDA’s vaccine adcomm VRBPAC and the CDC’s separate adcomm ACIP. “The process ultimately works in that science corrected some of the errors that were made. Yes, it might have been nice if they weren’t made in real time but I think the transparency helps.”
“The thing I wonder in the vaccine realm if we could have better coordinated things to essentially collapse the VRBPAC process with the Advisory Committee on Immunization Practices process,” he said. “We need to look carefully at this, ACIP was developed for routine vaccines and for that matter, for countermeasures not for the middle of an emergency.”
And in a country where there’s always been vaccine hesitancy, “that’s not the best time to have any air space between two advisory committees,” Marks said. “I think we as a federal government need to do a really good job to make sure our messaging is harmonized.”
The comments come as the FDA’s and CDC’s adcomms and leaders recently clashed over what groups of people should first receive booster shots following the recent EUA. Two of the top vaccine experts working under Marks recently announced their retirements were due at least in part to concerns with the way the booster EUA process played out.
On the medical device side, CDRH head Jeff Shuren noted that the EUA authorities have been incredibly helpful given the volume of products coming in through the door. “Without a national testing strategy, we’re doing all comers, rather than having a targeted approach,” he said. He also noted the EUA pathway was invaluable in speeding new tests and diagnostics, adding, “I really wish we had that flexibility in peace time.”