The COVID-19 pandemic’s direct and indirect toll on the human condition is beyond calculation, but the effect on FDA regulatory activity is easier to assess. The problem for device makers is that a number of draft and final guidances are stuck in a pandemic-driven regulatory limbo, which seemingly guarantees that some compliance and product development efforts will run afoul of the agency’s expectations and potentially delay a product’s market access.
The agency posted its annual guidance agenda for the fiscal year with the usual A and B lists for both draft and final guidances, although the persistence of the pandemic may create the impression that the items appearing on the B lists are little more than the subjects of wishful thinking. Nearly eight months of fiscal 2021 have passed already, and only two draft guidances have been posted thus far despite that the A list for draft guidances is populated by a dozen items.
Among the draft guidance items that are still in queue are those for computer software assurance and for the contents of premarket submissions for software in a medical device. Perhaps the key draft guidance for the pandemic, however, is the draft guidance for transitioning emergency use authorizations (EUAs) to conventional premarket filings. This is something the agency knows is needed, but the ongoing pressure of the pandemic has made it difficult to make any headway on this project.
Regulatory history a good starting place
Nathan Downing, associate regulatory attorney at Gardner Law of Stillwater, Minn., told BioWorld that the bottom line on this predicament is that while it is difficult to anticipate when a draft or final guidance might emerge, there are other ways to avoid straying out of regulatory bounds.
The answer to a general question might be inferred from existing guidance and previous regulatory filings, the latter of which is a particularly helpful source of information for class II devices. “When you have a very specific question, it’s going to be more work,” Downing said, adding that the pre-submission (pre-sub) process might be the best path forward if the unanswered question might prove critical to a premarket submission.
Downing said a question such as the planned adaptation of the Quality System Regulation (QSR) (as spelled out in Title 21, Part 820 of the Code of Federal Regulations), to align with ISO 13485 is another example of delayed guidance and hence uncertainty. He added, however, that most in industry will have both 13485 and 820 already encoded as part of their quality system.
Nonetheless, it may not be wise to go out on a limb with a revamp of a quality system in anticipation of what a rewritten Part 820 would look like, even for experienced hands. “If you are following both, stick with what you’re doing,” he advised, since this is less likely to create problems than trying to predict where the Part 820/ISO 13485 question will ultimately land.
The International Medical Device Regulators Forum also has a guidance agenda, which has experienced its own pandemic-induced drag. Trying to anticipate where IMDRF will go with a specific guidance is another hazard, particularly when this is a guidance the FDA will at least reference in its own guidances. This is especially the case for companies with a large footprint in the U.S. market.
An ordinary appreciation for regulatory best practices might recommend that the device maker not stray too far from the FDA’s current approaches when trying to anticipate what an IMDRF guidance will recommend, Downing said, but a modest deviation needn’t be crippling “if you can explain why you went the route you went.”
Downing said he hasn’t witnessed a lot of angst just yet over the EUA conversion guidance question, but noted that industry in general might be better off if the FDA keeps the scope of such a guidance fairly broad rather than try to draft a series of device type-specific sub-guidances. These conversions are likely to be complicated for at least some premarket applications, but Downing urged developers to remain mindful of the availability of pre-submission communication as a means of reducing the risk to investment for these transitioned products.
Duval: Guidance ‘the ultimate regulatory weapon’
Mark Duval, president and CEO of Duval & Associates in Minneapolis, told BioWorld that in his view, “guidance documents are the ultimate regulatory weapon.”
While both rulemaking and guidance development include a formal notice-and-comment function, Duval said the FDA’s consideration of comments for draft guidances “is often perfunctory at best, dismissive at worst.” In contrast to rulemaking, the agency does not have to explicitly address the feedback on draft guidances in final guidance documents, but Duval said another trade-off is industry’s inability to challenge a guidance document that may not comport with science, medicine or the law. This is because guidance is merely “an expression of FDA’s thinking at the current time. It is not meant to be ‘final agency action’ under tenets of administrative law, so it cannot be challenged in court,” he said.
On the other hand, Duval said a delay in the issuance of a final guidance gives the FDA “real time in the trenches, working and debating with sponsors to see how they may be improved.” While guidance is not subject to a legal challenge, he said there are administrative levers available to regulated industry, although in that scenario, it is “the FDA itself who plays the role of prosecutor, judge and jury – tough to win” that appeal, Duval said.