Avoiding the political overtones that seem to be more viral than COVID-19 these days, Anand Shah, deputy commissioner for medical and scientific affairs at the FDA, stressed that even though the agency is making decisions in real time in response to the urgency of the pandemic in the U.S., its decisions are being driven by scientific integrity, regulatory independence and the FDA’s historic commitment to ensuring the safety and efficacy of the products it regulates.

“While all of us want the world to return to normal as quickly as possible, it’s imperative that we do this process credibly and transparently and that the public has confidence in our decisions,” Shah said at an Alliance for Health Policy media event Thursday.

That includes the agency’s decision to hold off on granting an emergency use authorization (EUA) for convalescent plasma. Since convalescent plasma has been used for more than a century in a variety of diseases, the FDA has been supportive of investigating its use in treating COVID-19, Shah said. To that end, the agency launched a partnership with the Mayo Clinic, in which more than 60,000 patients will be enrolled in an expanded access protocol in a real-world setting.

Plasma is being evaluated in a host of other studies and the FDA has a scientific team, led by Center for Biologics Evaluation and Research Director Peter Marks, huddled around the issue. Through the federal government’s coronavirus task force, the FDA also is getting input from other agencies, including the NIH.

Anand Shah, deputy commissioner for medical and scientific affairs, FDA

Referencing media reports this week that suggested politics were at play in trying to speed an EUA for plasma, Shah said the agency’s decision to hold off on an EUA took into consideration several factors. “We will look at the totality of the data,” he said, adding that the eventual decision, whichever way it goes, will be based on safety and efficacy.

Building public confidence also will be crucial in a COVID-19 vaccine program as naysayers have been planting doubt based on the accelerated timeline for developing the vaccines and President Donald Trump’s expressed hope that a vaccine could be approved before the November election. While the FDA is expediting its review by assessing trial data as it comes in, Shah refused to speculate on when a vaccine might be licensed.

The FDA’s focus is on ensuring the integrity of rigorous vaccine trials, Shah said. Once it receives completed trial data, it will make licensing decisions based on the safety and efficacy of each candidate. To ensure transparency of the process and give it an opportunity to consult with external experts, the FDA has committed to convening its Vaccines Advisory Committee before a COVID-19 vaccine is licensed. Shah said an adcom meeting has been tentatively set for Oct. 22.

Given the novelty of the SARS-CoV-2 virus, “there’s always an element of risk and uncertainty,” Shah said. He noted that scientific understanding of the virus today is different from what it was even a month ago. Thus, the FDA’s response is dynamic, not static. There will be instances where the agency will have to revisit decisions as more is learned about the virus and the illness it causes. But the lessons learned will help shape the FDA of tomorrow and make it better prepared for future crises.

Progress made

Much of Shah’s presentation was an update of the FDA’s activities since the first COVID-19 case was reported in the U.S. Jan. 20, 2020. Fourteen days later, the CDC submitted the first diagnostic for the novel coronavirus. Within 24 hours, the FDA reviewed it and issued an EUA Feb. 4. Despite challenges with the CDC test and the growing need for more tests, the FDA received no other submission for fully validated tests until Feb. 29.

“It was evident that additional FDA action was needed to meet the unprecedented demand by the public and medical community for COVID-19 diagnostic tests,” Shah said. The agency streamlined its EUA submission process, updated templates and guidance, and created an infrastructure for validating test performance.

Those steps have promoted innovation in diagnostic technology, Shah said, even as the agency continues to monitor its testing policies, updating them as the evidence evolves. As of this week, the FDA has issued EUAs for more than 200 COVID-19 tests, including molecular diagnostics and antibody tests. The range of authorized tests use CRISPR gene editing technology, self-collected specimens and pooled strategies.

To accelerate the development of COVID-19 therapies, the FDA launched the Coronavirus Treatment Acceleration Program (CTAP) in March to triage incoming requests and proposals for potential COVID-19 therapies and match innovators with the appropriate FDA scientific and technical experts.

Besides accelerating review timelines during the pandemic, CTAP is providing important “lessons for modernizing the clinical research process for the post-pandemic era,” Shah said. The program has improved coordination within the agency and communication with sponsors, ensuring “they get the feedback they need to iterate and improve on protocol designs,” he added.

As a result of CTAP, more than 270 clinical trials had been initiated as of July 31, and another 570-plus clinical trials are in planning stages, representing a diverse COVID-19 pipeline of antivirals, immunomodulators, neutralizing antibodies and other types of drugs.

While holding to its standards for safety and efficacy, the FDA has found that reviewing data on a real-time basis allows it to make decisions with unprecedented speed. For instance, the agency issued an EUA for Gilead Sciences Inc.’s remdesivir about 48 hours after receiving the preliminary trial data, Shah said. That rapid action enabled the NIH to update its clinical guidelines for treating COVID-19 and allowed the Department of Health and Human Services to develop an allocation and distribution plan for the drug.

Although responding to the pandemic remains its top priority, the FDA is meeting its other goals – despite the heavier workload. It is on target to meet its drug user fee goals for the year by reviewing and taking timely action on at least 90% of brand, generic and biosimilar drug applications, Shah said. That includes approval of more than 30 new cancer drugs.

To make sure the agency learns the lessons being taught by the pandemic, FDA Commissioner Stephen Hahn this month launched the COVID-19 Pandemic Recovery and Preparedness Plan (PREPP) initiative with the goal of identifying “durable improvements in policy, process and program operations to both accelerate the recovery from COVID-19 as well as strengthen the agency’s preparedness for future emergencies,” Shah said.

PREPP will start with interviews with key staff and stakeholder feedback. The agency will then identify key priority areas for change and develop a plan for introducing improvements and modernization to regulatory processes, operations, communications and intra-agency coordination.

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