The annual med-tech conference hosted by the Advanced Medical Technology Association, always features an FDA town hall, but this year’s town hall labored under the overhang of the COVID-19 pandemic. Nonetheless, Jeff Shuren, director of the Center for Devices and Radiological Health (CDRH), repeatedly gave voice to frustration with the statutory authorities currently enjoyed by the center, stating on more than one occasion that the Medical Device Amendments of 1976 are more than 40 years old and are in need of updates to cope with modern medical technology.

Shuren highlighted some of the developments arising from the COVID-19 pandemic, adding that regulatory flexibility has proven critical to the U.S. FDA’s response. On average, the agency has granted an emergency use authorization (EUA) for a diagnostic or surveillance test per day since the pandemic began, he said, noting that CDRH staff have also issued 23 guidances and 10 EUA templates for testing.

Shuren said the current premarket regime is a stage-gated approach that is growing increasingly cumbersome, and that the flexibility needed for urgent situations is not sufficient outside the EUA mechanism. There are several considerations regarding statutory updates, including those needed for the pre-certification program for software as a medical device (SaMD), although the need for a more expansive regulatory regime is broader than that, he said. Those updates along with a more modern IT system, will allow the CDRH staff to respond more rapidly to urgent considerations.

Review times slipping, backlogs forming

Shuren said the center had to de-prioritize some of the work it had anticipated completing this year, which includes guidance development. However, premarket reviews are starting to drag out as well. “We are starting to see our performance [in premarket review times] starting to slip,” he said, adding that this is creating a backlog for PMA filings, which is likely to grow before the agency can reverse the trend. This problem affects 510(k) submissions as well.

The SaMD pre-cert pilot “has been incredibly informative,” Shuren said, but while the pandemic has hampered development of the pilot, some of the changes needed would require a tweak of the statute. Given that dilemma, the FDA is considering whether it should think more expansively about regulation of devices generally, although Shuren did not cite regulation of lab-developed tests in this discussion.

Bill Maisel, chief scientific officer at CDRH, said Part 820 quality systems requirements and unique device identifier (UDI) requirements will both eventually kick back in, but the agency will come up with a draft guidance for how these will be reinstated. Pre-approval inspections for PMA devices have not disappeared during the pandemic, but the agency has tried to devise methods of dealing with these inspections, including the use of the results of data from prior inspections of the facility. This approach is easier when the agency has prior experience with the product and/or the facility, Maisel said, and Shuren said the notion of key performance indicators as seen in the pre-cert program may be useful in this context in times to come.

The management committee at the International Medical Device Regulators Forum (IMDRF) is not completely sold on the Medical Device Single Review Program (MDSRP), Shuren said, but the FDA is still working to integrate the findings of Medical Device Single Audit Program (MDSAP) audits into its oversight of device manufacturing facilities. The FDA is at something of a disadvantage for MDSRP in some respects, due to a regulatory difference in the premarket realm, but Shuren said the agency is working to rationally harmonize some aspects, such as more extensive use of performance standards. CDRH is undertaking a rework of the third-party review program to ensure greater reliability of those reviews, and Shuren said a more vigorous post-market data collection effort may help to facilitate the harmonized single review concept.

Shuren said the least burdensome flag program for premarket reviews has generated 14 or so flags over the past year. Some of these flags did not qualify under the terms of the program, but the remaining flags were resolved as issues on the part of the sponsor and/or the FDA review team. Regardless of the results of a given flag, he said these actions bring senior staff into these controversies and thus offers a learning opportunity for all parties. “We continue to look at ways to ensure that if there is a difference of opinion, that it’s raised and we look at it,” he said, encouraging sponsors who do and do not raise the flag to “work with the team, but if there’s a difference of opinion … bring that to the attention of managers.”

The agency’s work on the convergence of the FDA Quality Management Systems (QSRs) and ISO 13485 has also suffered from the distraction created by the pandemic, but Shuren was reluctant to predict when a draft rule would emerge. The most he would commit to on the timeline was “after this week.”

Amin blasts criticism of EUAs

Another event taking place on Oct. 6 was the first day of the annual meeting of the Food and Drug Law Institute, and FDA chief counsel Stacy Cline Amin was less than impressed with some of the criticism leveled at the agency thus far in the pandemic. Amin indicated that she found it ironic that some of those who criticized the FDA for allowing more serology tests onto the market than was perhaps appropriate also took the agency to task for not allowing lab-developed tests (LDTs) on the market unless they went through the EUA process.

Amin said the data for hydroxychloroquine met the standard for an EUA nod at the time the agency granted the authorization, adding that the EUA for convalescent plasma is backed by data that still meet the EUA standard. The convalescent plasma EUA “has also been unfortunately politicized,” she said, adding that the agency’s experience with hydroxychloroquine prior to the pandemic was extensive. She noted that the data depicted this treatment as a low-risk proposition, adding that it was authorized for in-hospital use only.

Amin said the regulatory benefit-risk calculus for a vaccine is different than for a therapy, adding that the agency’s handling of this will hew to the standards for biologics license applications rather than those for conventional drugs. “FDA has not raised the bar for an EUA as has been reported” in connection with a vaccine, she said, adding, “there is not a single person at the FDA who would stand for” authorizing or licensing a vaccine on sub-par data.

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