U.S. FDA warning letters have been a staple of regulatory life since the late 1990s, but James Boiani, a regulatory attorney with Epstein, Becker & Green P.C., said it’s no stretch of the imagination that warning letter volumes will jump in 2021. This is to some extent because the volume of warning letters dropped significantly over the past four years, and Boiani advised that all FDA-regulated industries will see more warning letters unless they are communicative with the agency about inspectional findings.

The FDA and several other federal agencies were active in the enforcement space early in the COVID-19 pandemic, as demonstrated by a March 2020 statement by the FDA and the Federal Trade Commission about fraudulent products. The enforcement focus at the FDA for 2021 is likely to continue to be on products related to the COVID-19 pandemic, and Boiani predicted that drug compounding issues will return to the fore, at least in terms of manufacturing quality and patient access. Warning letter volumes had dropped by about 90% under the Trump administration, and he said all FDA-regulated industries are “more likely to see FDA 483s elevated to warning letters if companies are not being responsive to requests” about their compliance with good manufacturing practices.

MCIT unlikely to fall under regulatory review

Boiani, who spoke during a Feb. 3 webinar hosted by Medmarc Insurance Group of West Chantilly, Va., said the Biden administration’s Jan. 20 regulatory freeze could affect the Medicare Coverage for Innovative Technologies (MCIT) coverage rule for FDA breakthrough devices. “If you’re in the device space, this is one to watch,” he said, despite that the Biden administration may not see this as a top priority for reconsideration.

The Biden administration is likely to resort to legislation for FDA regulation of lab-developed tests (LDTs), which has been proposed in each of the past two iterations of Congress. The previous administration had issued a rescission order in connection with FDA regulation of LDTs, but Boiani noted that any significant problem with LDTs within the scope of the pandemic would add fuel to the legislative fire for a bill that would enable FDA regulation.

Conversely, if there are no issues with these tests and the FDA cannot get up to speed on its reviews of tests for the SARS-CoV-2 virus, legislative action will be less likely this year. Labs will point to the pandemic-driven backlog in emergency use authorization (EUA) reviews as evidence that the FDA is not staffed and equipped to handle the sizeable increase in premarket filings that would ensue if legislation were passed.

Review times for drugs, biotech products, devices and diagnostics that are not directly related to the pandemic will continue to experience drag in 2021, Boiani said. He said he has personally witnessed instances in which the FDA recommended the sponsor delay filing a premarket application for as long as two months to give agency reviewers time to prepare for the filing. The Biden administration may have a two-pronged approach to this, consisting in increases of FDA staff and in the use of third-party reviews.

Assuming this plays out as expected, user fees “will be similar to what they are now,” Boiani predicted, adding that the White House may try to prod Congress to allocate more appropriated monies to the FDA centers’ premarket review offices instead of pushing industry for substantially larger user fee volumes. He predicted that user fees in the next user fee schedules will be “near-ish to where they are now, maybe ten percent to fifteen percent up from where they are now.”

PREP Act not going away anytime soon

Insulation from product liability under the Public Readiness and Emergency Preparedness (PREP) Act is likely to remain in place, Boiani predicted, and the administration is unlikely to narrow the scope of the Act. Because of the ongoing problems posed by the pandemic, the White House “will be very reluctant to change things in any way that could increase risk to manufacturers,” which might cause some companies to leave the marketplace, while others would reconsider any notion of entering the marketplace. The PREP Act may be sustained through 2024 because the pandemic is likely to still be a significant public health problem until then, Boiani predicted, particularly given the amount of time needed to inoculate the public for the legacy SARS-CoV-2 virus and its recently emerging offshoots.

There will be “a tremendous push” to bring more of the drug and device manufacturing supply chain back to the U.S., Boiani said, adding that the domestic share of manufacture of active pharmaceutical ingredients is especially salient. There may be some bipartisan legislation on Capitol Hill, particularly given that both President Biden and Sen. Tom Cotton (R-Ark.) agree in principle on this point.

The FDA’s role in this situation will be to encourage the use of novel manufacturing equipment for APIs and finished drug products, something acting FDA commissioner Janet Woodcock has discussed. Woodcock was the director of the Center for Drug Evaluation and Research before taking part in Operation Warp Speed, and then taking the acting commissioner’s role upon the departure of Stephen Hahn in late January.

Human factors engineering for devices in general and diagnostics in particular has been the source of some interest on the part of the FDA. The agency has demonstrated a greater willingness to consider human factors data as a substitute for standard test performance studies when the site of service is different and/or the staff are different. Much of this flexibility is from CDRH director Jeff Shuren, but the increased flexibility may come with a greater demand from CDRH for human factors studies for a broad series of device types, including some class I devices. However, Boiani advised that the plaintiff’s bar may leverage these new demands in product liability litigation, particularly for drug delivery systems.

The directors of the product centers might not be subject to any churn under the Biden administration, Boiani stated. Shuren, whose tenure as the director of the Center for Devices and Radiological Health (CDRH) has eclipsed the 10-year mark, has demonstrated a sustained belief in the benefits of innovation and of transparency, which may insulate Shuren from any inclination on the part of the next FDA commissioner to replace him.