The COVID-19 pandemic has demanded much of the FDA, and commissioner Stephen Hahn said on a June 1 conference call that “there have been hiccups along the way” as the enormity of the threat came into view. The agency’s use of emergency use authorizations (EUAs) has drawn criticism, but Hahn defended those EUAs and other regulatory flexibilities even has he declared that the FDA is not “walking away from” randomized, controlled clinical trials as the gold standard for premarket review.

The conference call was moved up one hour on the morning of the event, and Hahn took no questions from those in attendance, suggesting perhaps that his agenda for the day had changed at the last minute. He thanked the members of the Alliance for a Stronger FDA, which co-sponsored the briefing, for their role in aiding the agency’s public health mission.

While the pandemic has forced the FDA to adjust some of its processes, Hahn said the agency will at some point examine how it reacted to the pandemic with an eye toward a more efficient regulatory apparatus. The design and conduct of clinical trials is also a point of interest, and Hahn said master protocol development undertaken in response to the pandemic won’t become a thing of the past once the pandemic is over. He cited the need to demonstrate flexibility to allow patient access to clinical trials for COVID-19 therapies, however, although that flexibility is not a signal that randomized, controlled trials (RCTs) have fallen into disfavor at the FDA.

Some regulatory changes were already in process

Some of the permanent changes that may in hindsight seem to have been brought on by the pandemic were already underway, Hahn said, listing decentralized clinical trials as one of these regulatory innovations. The use of telemedicine in trials is also a point in this area, but Hahn said he has “great hopes in the future” for the use of real-world evidence. Several ongoing FDA data gathering efforts, such as the Sentinel system, have been used by the agency to retrospectively evaluate some of the EUA tests, and Hahn said, “there are some very important lessons there for us,” such as test validity and supply chain issues. “I believe we will have more confidence in the use of real-world evidence moving forward,” he said.

One of the organizational changes at the FDA is that Janet Woodcock, director of the Center for Drug Evaluation and Research, has temporarily stepped away from that post to aid in Operation Warp Speed, the public-private partnership designed to accelerate development of therapies and vaccines for the SARS-CoV-2 virus. Peter Marks, director of the Center for Biologics Evaluation and Research, will resume his duties at CBER after overseeing the vaccine development effort at Warp Speed, and Hahn said he and Marks will remain outside of any decision-making regarding products that go through the Warp Speed program.

Hahn went on to address the reasoning behind the agency’s moves to streamline the various premarket review mechanisms under the EUA mechanism, stating, “it was clear to all of us that some FDA processes needed to be adjusted” in the midst of the pandemic. FDA staff will scrutinize the impact of the FDA’s midstream adjustments when time and circumstances permit, he said, adding that one of the instructions to FDA staff is “how to permanently make FDA more efficient in carrying out its responsibilities.”

As the pandemic unfolded, “I pledged to the agency and to myself that we would continue to have all our decisions rooted in science,” Hahn emphasized, although the pandemic has highlighted the risks and benefits of the related products in a different light. Consequently, the underlying data “might not be as robust as they would be” under normal circumstances, he said.

Hahn said teleworking still accounts for a large share of FDA activity, and that he has consulted with others outside the agency in dealing with the pandemic, including former FDA commissioners. Those former FDA commissioners have urged that Hahn lean heavily on the expertise inside the agency while those outside the agency have recommended that Hahn direct the FDA staff to move quickly and transparently to address the pandemic. “I am confident that the FDA has measured up to this unprecedented challenge,” Hahn said, adding that the lessons-learned effort will commence in time to be useful by the time a second wave of COVID-19 emerges later this year.

Hahn cites ‘essential role’ of diagnostics

The media coverage of the pandemic has been extensive, Hahn noted, adding, “there has been a lot in the press about FDA’s role, particularly around diagnostic tests.” He said the agency has worked to prevent sale of fraudulent products in addition to allowing legitimate products to enter the market. However, he noted, “if there’s one thing I think has been reaffirmed in this crisis, it’s the essential role of medical devices, including diagnostics, in countering this pandemic.”

By the beginning of March, roughly 50,000 tests for the pathogen had been performed, but Hahn said that number will surpass 17 million as of June 1, which he characterized as “an unprecedented expansion in testing capacity.” The FDA has “worked and will continue to work with the private sector, and believes very strongly the private sector will help us through this, particularly on the diagnostic test side,” Hahn said. The agency had commenced with collaborative efforts with diagnostic companies as early as Jan. 22, 2020, he said.

The U.S. National Strategic Stockpile has seen an increase in inventory for several items, including ventilators, Hahn said, adding that the percent of U.S. citizens testing positive is now at about 6% nationally. The target figure for positive testing has been 10% or less, a figure presumed to indicate that the volume of testing is sufficient to provide a fairly accurate epidemiological assessment of the pandemic. Any questions about test reliability will prompt the FDA to take action, but he said this process “is continually being informed by data and science.”

The FDA is working in a similar fashion on vaccines and drugs, and Hahn said more than 90 pharmaceutical therapies are under investigation at present. However, there is a limited capacity in the research infrastructure, and thus the agency sought to prioritize applications that bear “the greatest scientific merit,” he said. Three companies have vaccines in one stage or another of trial, and the objective of Operation Warp Speed is to have a vaccine ready to go sometime during calendar year 2020 or shortly thereafter. This is a very ambitious timeline and Hahn said the agency may once again be faced with risk-benefit decisions based on less data than would be available under ordinary circumstances. Remdesivir, the broad-spectrum antiviral by Gilead Sciences Inc., of Foster City, Calif., went from clinical trial for SARS-CoV-2 in February to emergency use authorization May 1, Hahn noted.

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