- FDA has issued a final rule intended to clarify and formalize the De Novo process that allows some medical devices without a predicate to bypass the premarket approval pathway.
- The medtech industry welcomed the broad goals of the proposed rule published late in 2018 but pushed back hard against some of its provisions, notably with regard to FDA's plans to carry out premarket manufacturing inspections.
- FDA, while making some tweaks to the draft, held firm on the main points of friction with the medtech industry, arguing that it is legal and necessary to inspect some facilities as part of the De Novo process.
Early last year, AdvaMed sent feedback that welcomed FDA's aim to enhance the "regulatory clarity and predictability" of the De Novo pathway through the proposed rule but found fault with the specifics. The medtech trade group raised concerns the rule would impose requirements that replicate the PMA process. As AdvaMed saw it, a "drift towards PMA review is discordant with the De Novo classification process' purpose" and would lead to "unnecessary expenditures."
"The most controversial aspect was FDA's provision for ... an FDA inspection for what is tantamount to a 510(k)," noted Bradley Merrill Thompson, attorney at the law firm Epstein Becker Green in an email.
Thompson called that "a real stretch," but the FDA resisted siding with industry.
AdvaMed objected to plans to inspect some facilities before the De Novo decision because it argued FDA lacks the authority to make quality system inspections a prerequisite to classification or deny a reclassification based on a facility visit. The trade group asked FDA to only inspect facilities after making De Novo decisions.
FDA disagreed. In response, the agency set out the two circumstances when it would inspect facilities, namely when data integrity and quality concerns arise during its review of a De Novo request and when devices have critical or novel manufacturing processes that may affect the safety and effectiveness of the product.
The agency clarified it will only perform inspections to ensure data "were collected in a manner that ensures the data accurately represents the risks and benefits of the device" when it has reason for concern, such as if the results seem "clinically or physiologically improbable" or a whistleblower has alleged misconduct at clinical trial sites. FDA also clarified that the proposed manufacturing inspections are not to assess compliance with the Quality System Regulation.
FDA only expects to inspect "a small percentage" of De Novo requests but sees site visits as essential in those circumstances. As such, FDA made "clarifying changes" in response to the feedback but kept the right to inspect facilities before De Novo decisions.
AdvaMed's other objection centered on FDA's requirement for applicants to submit all information "known or reasonably known." The trade group said the "standard is unclear and creates difficult questions for requesters," such as who decides what is "reasonable," and raised concerns the requirement could lead FDA reviewers to think applicants are "hiding something."
To resolve the perceived problems, AdvaMed called on FDA to change the phrase to "known by or reasonably available to the requester."
FDA found its own problems with that phrase because the requester may know of studies or reports about the safety and effectiveness of a product but not be able to obtain them, for example because it must pay to access a registry. In such cases, FDA wants the requester to share what they know even if complete information is unavailable.