FDA’s Draft Guidance on the Q-Submission Program – A Step in the Wrong Direction

FDA recently issued a draft guidance on Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program, which included some changes over the existing guidance which could have a negative impact on future pre-submissions.

The draft guidance attempted to clarify when a Sponsor’s question may be more appropriate for more informal communication.  The guidance recommends that questions “that can be readily answered” based on the FDA reviewers “experience or knowledge” and that “do not require additional background information, an in-depth review, or other FDA staff involvement” can be done outside of the Q-Submission process.  This hardly provides clarification and seems to limit the topics that could utilize this method of feedback.

In addition, the draft guidance, incorporated the 1998 guidance on PMA Day 100 Meetings.  The PMA Day 100 meeting may be used to discuss clarifying questions about Major Deficiencies and preliminary approaches for a response.   However, instead of committing to continued communication with the applicant every 4 weeks until the review is complete, FDA recommends the applicant submit a Submission Issue Request (SIR) to enable further discussion of a detailed  approach to addressing major deficiencies. It is not clear from the draft guidance how the timetables noted in Table 1 for an SIR would relate to an SIR submitted after the PMA Day 100 meeting.  However, Table 1 states that if the SIR request is received within 60 days of the FDA “marketing submission letter” FDA would, resources permitting, have the meeting or provide written feedback within 21 days.  It’s not clear, though, how SIR’s submitted after 60 days would be handled in the context of a post-100-day meeting interaction because some of those interactions would exceed 60 days, and per Table 1, FDA wouldn’t hold a meeting for 70 days after receiving such a request.  If this is FDA’s intent, it would be a major change to the process as set out in the 1998 Guidance allowing for monthly interactions.  In addition, the draft guidance indicates that “relevant review team members and management will attend the meeting with the applicant as well as other FDA staff as appropriate,” whereas the 1998 guidance states in addition to the relevant core review team, the Branch Chief, Division Director, or Deputy Director will attend the meeting with the applicant.

The draft guidance also provides additional detail on the number of questions that can be addressed within one pre-submission. FDA indicates that a pre-submission with too many topics does not result in productive discussions or feedback. The draft guidance echoes the existing guidance in that the pre-submission should be limited to 3-4 topics; however, the draft guidance goes further and recommends a limit of 7-10 questions across those topics.  In addition, the draft guidance offers some considerations regarding the types of questions and information necessary for FDA to provide feedback.  If the Sponsor submits an “excessive number of topics”, FDA may contact the Sponsor to discuss which topics should be prioritized and which topics can be delayed in a subsequent pre-submission.

The draft guidance further provides considerations for the type of questions to ask in a pre-submission.  For example, if the questions are related to regulatory pathway or indications for use, it may be too early to ask questions about performance data.  This seems misguided, as feedback on required performance data may shape the Sponsor’s decision on the final indications for use and claims for the device.  Similarly, if the design is not frozen and the Sponsor expects to make “technological changes” to the device, according to the draft guidance, it may be “premature” to ask questions about performance data. However, getting input on the design and performance testing plan at the time of the pre-submission can provide valuable insights to a Sponsor and may even direct changes to the design that were not anticipated. Conversely, waiting until the device is out of the design stage may be too late to first get input and alignment on required performance testing. Once the final device has been designed, Sponsors typically move quickly into executing performance testing (e.g., design verification and validation). For questions related to clinical study protocol, the draft guidance recommends that Sponsors provide the planned indications for use and describe the non-clinical data that will be included in a subsequent marketing application. With the increasing number of pre-submissions submitted to the Agency, it is not surprising that FDA added even more language restricting the scope and review of a pre-submission.

This draft guidance is open for comments through May 14, 2024, which can be submitted online.  We hope the final guidance provides more clarity on use of informal interactions with the Agency as a method of getting feedback.  We consider the focus on limiting the number of questions that can be addressed in any one pre-submission and the impact that will have on development timelines to be a step in the wrong direction.  The approach to submitting a pre-submission with a limited number of questions and following with additional pre-submission supplements to get feedback and alignment with the agency on a variety of topics does not align with helping ensure timely access to new medical devices. This approach, further, seems outdated given many Sponsors utilize agile-like approaches to medical device development focusing on flexibility, rapid iterations based on customer-centric feedback (including regulator feedback), and speed to market.  The pre-submission process is a useful tool for Sponsors to gain alignment on expectations upfront and early in the development process.  We hope FDA does not limit the utility of this valuable resource and instead considers how it can continue to collaborate early and often with industry to streamline and not prolong the development process.