How COVID-19 is Changing FDA Approval and Clearance Processes

FDA Approval

The COVID-19 pandemic is changing the FDA irrevocably, resulting in a more dynamic, streamlined FDA that is more willing to embrace digital technology, according to panelists at the recent OC LIFe (Lifesciences Innovators Forum) virtual presentation, “COVID-19: Changes In FDA Approval & Clearance Processes.”

When President Trump’s Operation Warp Speed and the FDA’s emergency use authorizations (EUAs) went into effect, the FDA was inundated with submissions and worked round the clock. Many companies submitting plans for FDA review received turnarounds in 36 hours or less. “There was urgency in the emergency,” Shep Bentley, principal consultant, Bentley Biomedical Consulting, said during the panel discussion. “Now there’s an enormous queue for EUA reviews.”

Underscoring that inundation, Allison Komiyama, principal consultant, AcKnowledge Regulatory Strategies, shared an excerpt from an FDA letter: “CDRH has received more than 2,000 pre-Emergency Use Authorization (pre-EUA) requests and this has led to a significantly increased workload. However, due to our current resource limitations, we are currently unable to conduct an in-depth review of your submission and provide detailed feedback.…We are notifying you that your Q-Submission is closed.”

To speed review, the FDA provides template documents in Word format for dynamic, interactive submissions. The FDA will point out needed changes, but it is not your subject matter expert. Helping you determine claims or what the final product should look like is not its role. “You still need your ducks in a row,” panel moderator Piet Lesage, principal consultant, GB5D, stressed.

Panelists advised filing a pre-EUA, as it enables FDA staff to sassing a number and sequence the submission for review. Expect a response to take about a week.

Guidance documents are being issued at a dizzying pace, too.

“Since March, there have been 53 guidance documents with ‘COVID’ in the title,” Komiyama said. Some, like the enforcement policy for non-invasive monitoring devices, were updated within a few months of being issued. Many were related to digital health and to devices to treat psychiatric disorders, “believing the benefits outweigh the risks,” she explained. Often these products went to market without full FDA reviews.

“It’s a dynamic situation,” Bentley stressed. Consequently, companies must plan based not only on the guidances, but on the trends. “Anticipate what the situation will be like when you complete the evaluation. If you look only at recent guidances you’re probably missing some criteria.”

Facility inspections also are in flux. Between March and July, the FDA temporarily suspended on-site facility inspections, Jesse Kryger, VP, regulatory affairs and quality assurance, PTS Advance, added. Then, “In July, it announced it was resuming inspections for high-risk, class III devices.”

Nonetheless, many companies are facing virtual site inspections. For example, the Medical Device Single Audit program began before the pandemic to allow companies operating in multiple countries to have a single audit that met the needs of multiple nations’ regulators.

“In January, the FDA piloted a remote version of that audit. Now the FDA permits fully remote audits,” Kryger said. “It’s a challenge for the industry because it requires significant planning around the technology (in addition to the audit),” for such details as how to use cameras to conduct a virtual tour of the facility. Currently, even with a remote audit, facilities must undergo a full, on-site audit within one year, “assuming the pandemic ends,” Kryger said.

Audit disruptions extend to the supply chain, too.

“Companies have challenges to onboard, quality and continuously monitor their CMOs and suppliers, especially when travel is restricted and there are incentives to reshore (operations),” Kryger said.

For drug and device manufacturers, “The idea of leveraging the pandemic to ease entry into markets is commonplace,” Bentley said.

Panelists reported being approached by several companies asking whether to pivot to produce COVID-related products that may be ready in two years.

“The answer is ‘No,’” Komiyama said. “The FDA is looking for products that are ready to go now.”

EUAs today apply only to products directly related to COVID-19. For instance, a home diagnostic that may relieve pressure on the healthcare system doesn’t qualify for an EUA unless it’s a COVID-19 diagnostic.

When President Trump invoked the Emergency Defense Act last spring, car manufacturers shifted to produce ventilators. Working in that environment and under an EUA, manufacturers are exempted from some of the normal requirements for medical device manufacturing. To continue manufacturing those products after the pandemic ends, “They will need to come into compliance with the FDA’s quality system regulations, Kryger said.

Unless they meet the usual FDA requirements, once the emergency declaration ends, companies no longer will be able to sell products approved under an EUA.

“The details will be shared nearer the end of the emergency, and we’ll have months of advanced warning,” Bentley pointed out. “The FDA has told us we probably aren’t even 10% of the way through the emergency. This will go on for years.”

Underscoring that point, Komiyama added, “EUAs are still in place for anthrax, Ebola, SARS, and MERs.”

Preparing for normality matters, though. Collect real world evidence now for use in premarket submissions after the emergency declaration ends, Komiyama said. That way, there won’t be a lapse when the emergency declaration ends.

Kryger advised companies to develop quality systems, even though they are not required under EUAs. This prepares them to consistently produce products that meet stringent specifications after the emergency ends, and makes them more attractive for potential partners and for acquisitions.

The FDA is undergoing rapid, fundamental changes in the face of significant challenges. It has given the agency an opportunity for amazing innovation. After this year’s precedents, Komiyama said, “It’s hard to get the cat back into the bag. We are never going back to normal. The FDA will come out of this an evolved agency, with a changed regulatory landscape.

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