EMERGO SUMMARY OF KEY POINTS:

• US FDA has updated guidances on its premarket review appeals process and for market application deficiency letters.
• The agency has more clearly defined terms including “significant decision” and “substantive summary” for medical device market applicants appealing regulatory decisions.
• The agency has provided clearer recommendations for responding to deficiencies in premarket applications, as well.

The US Food and Drug Administration’s Center for Devices and Radiological Health (CDRH) has updated guidance documents covering appeals processes and procedures for medical device premarket review decisions, as well as for developing requests for additional information for FDA registrants whose applications are deemed deficient.

First, CDRH has updated guidance on its appeals process for premarket reviews as mandated by the 21^st Century Cures Act of 2016. The update covers three key questions:

• What is a “significant decision?”
• What is a “substantive summary?”
• Who may request documentation regarding CDRH premarket review decisions?

Significant decisions

According to Section 517A of the Food, Drug & Cosmetic Act (FD&C Act), which covers documentation and review procedures related to CDRH 510(k), Premarket Approval (PMA) and other device premarket review decisions, “significant decision” has no specific definition; however, US regulators consider the following instances as significant decisions:

• 510(k) substantial equivalence determinations
• PMA and Humanitarian Device Exemption (HDE) approval decisions
• Granting or denial of 515c breakthrough devices
• IDE approval decisions
• Failures to Reach Agreement on a protocol under FD&C Act Section 520(g)(7)
• Clinical Hold decisions according to FD&C Act Section 520(g)(8)

CDRH applies the same timeframes and procedures used for 517A premarket decisions to requests for supervisory review of these decisions, according to the guidance. However, some regulatory actions do not qualify as 517A decisions and are handled according to 21 CFR Part 10.75. Examples of decisions that do not fall under 517A auspices include 510(k) requests for additional information, PMA major deficiency letters, 510(k) and warning letters.

Substantive summaries

Under Section 517A, substantive summaries of scientific and regulatory rationale for a premarket decision must be provided by CDRH upon request by a US medical device market applicant. The summary should include documentation showing that the regulator applied least burdensome requirements in order to reach its decision.

Components of a substantive summary should include:

• Explanation of regulatory decision rationale
• Explanation of how least burdensome requirements were applied to a decision
• Documentation regarding significant controversies and/or differences of opinion and how those issues were resolved
• References to literature and standards relevant to the regulatory decision

Who may request information on 517A decisions

Finally, the updated guidance states that any applicant that has submitted or is planning to submit a 510(k), PMA or other medical device registration for CDRH premarket review may request a substantive summary of a 517A decision pertaining to that applicant’s own device without having to file a Freedom of Information Act (FOIA) request.

Deficiencies and Least Burdensome Requirements

In a separate recently updated guidance, CDRH has clarified procedures whereby regulatory staff develop and issue deficiency letters to US market applicants to meet Medical Device User Fee Amendments of 2017 (MDUFA IV) requirements.

The guidance covers principles including least burdensome requirements that CDRH reviewers should follow when identifying market application deficiencies, but also recommendations for how applicants should respond to deficiencies cited in their submissions.

Recommendations for industry include:

• Addressing all deficiencies from FDA within the timeframe specified in the deficiency letter
• Restating the issue raised by FDA reviewers in applicants’ response
• Providing either the data requested by the deficiency letter; an explanation for why the applicant believes the deficiency is irrelevant to the marketing authorization decision; or alternative information along with an explanation as to why that information resolves the deficiency

Additional US FDA resources from Emergo:

• US FDA consulting support for medical device and IVD companies
• FDA Form 483 warning letter response and recovery support
• Whitepaper: Early communication with the US FDA
• Whitepaper: Determining Substantial Equivalence for FDA 510(k) clearance