AdvaMed Calls for Definitional Clarity on Meaning of 'Significant Decision' in Recall Guidance

The US medical device industry is weighing in on a long-awaited guidance document released in May 2013 by the US Food and Drug Administration (FDA) regarding the appeals process to be used by device companies whose applications for approval or clearance have been rejected by the agency, saying additional definitional clarity is needed.

Background

FDA has been working to revamp its appeals process for several years now. Starting in late 2011, the Center for Devices and Radiological Health-the center that reviews most medical device applications-released the draft of its CDRH Appeals Process guidance, which said it aimed to provide clarity for those in industry who wanted to appeal an adverse decision, such as the denial of a premarket approval (PMA) or 510(k) premarket notification application.

The guidance document is intended to replace two earlier guidance documents:

• Medical Device Appeals and Complaints: Guidance for Dispute Resolution (February 1998)
• Resolving Scientific Disputes Concerning the Regulation of Medical Devices, A Guide to Use of the Medical Devices Dispute Resolution Panel; Final Guidance for Industry and FDA (July 2001)

On 16 May 2013, FDA released a finalized version of that draft guidance, incorporating both a range of comments from the medical device industry and new requirements dictated by the Food and Drug Administration Safety and Innovation Act (FDASIA).

In addition, FDA also released a question-and-answer guidance document regarding its draft interpretation of Section 517 of FDASIA, which requires FDA to have specific processes and timelines for appeals of "significant decisions" of 510(k), premarket approval (PMA) and investigation device exemption (IDE) applications.

Why the Q&A document? Because FDASIA left one important definitional component up to FDA: the meaning of the term "significant decision" and how that would affect the appeals process.

Q&A Basics

FDA's accompanying guidance on 517A "significant decisions" explains that FDA has defined the term to mean the following:

• finding a 510(k) to be not substantially equivalent (NSE)
• finding a PMA or Humanitarian Device Exemption Application to either be not approvable or approvable with conditions
• finding an IDE application to be disapproved
• failure to reach an agreement regarding a protocol under Section 520(g)(7)

An approval decision or any of the previous that is not satisfactory may also be appealed as a "significant decision," FDA said.

Also important to sponsors is FDASIA's requirement that FDA provide, upon request, a "substantive summary of the scientific and regulatory rationale for any significant decision regarding such submission, including documentation of significant controversies or differences of opinion and the resolution thereof."

FDA said it takes the term "substantive summary" to include the following elements:

• an explanation of the rationale for the regulatory decision
• documentation of significant controversies or differences of opinion, i.e., ones the resolution of which had a direct bearing on the regulatory decision
• references to published literature and consensus standards upon which the decision-maker relied

Industry Weighs in-Again

Now the medical device industry standard-bearer, the Advanced Medical Technology Association (AdvaMed) has again weighed in on the appeals process, recommending that FDA clarify certain definitions within the new Q&A draft guidance.

The group had earlier weighed in on the main appeals draft guidance, primarily raising concerns about the role of the CDRH ombudsman.

Now, though, it's focusing more on FDA's definition of "significant decision," noting that FDA's guidance fails to mention that a Clinical Laboratory Improvement Act (CLIA) waiver denial could, in its decision, be a "significant" setback.

In addition, AdvaMed argues FDA should explicitly state that applicants can "request supervisory review" for other "important" decisions that take place earlier in the regulatory review process under 21 CFR 10.75. In other words, just because it didn't involve a 510(k) or PMA decision, doesn't mean it wasn't an integral factor in the non-approval of a product application.

"We note these decisions should not be termed 'non-significant,' which would diminish their critical importance in the regulatory review process and potentially infer that an applicant is barred from requesting information about the scientific and regulatory rationale for a decision in pursuit of resolving a dispute during supervisory review," AdvaMed wrote.

Further, AdvaMed said it was unclear from the guidance when a company would actually receive a substantive summary. While FDA must come to a decision within a certain number of days, when that decision (and its documentation) is relayed to companies was left unspecified, according to AdvaMed.

An additional point of clarification sought by AdvaMed regards the review timing for significant decisions, which are meant to be expeditious. While the group said it appreciated FDA's guidance being explicit on this point, it argued that "all supervisory decisions, whether a significant decision or otherwise, should be handled in an expedient manner."

"While we believe this is the Agency's intent and understand the need for the Agency to prioritize resources, it is critical to follow reasonable timeframes for any decision appealed to FDA," it wrote.

The comment period on the draft guidance ended on 15 August 2013, meaning additional comments may soon be posted to FDA's docket on the document.

AdvaMed Comment

Draft Guidance for Industry: Appeals Processes: Questions and Answers About 517A