Background
As we noted in our recent Medical Device Update,[1] on February 18, the U.S. Food and Drug Administration (FDA or the Agency) issued a final guidance titled “Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff” (Guidance).[2] This Guidance contains substantive changes from the pre-submission (Pre-Sub) draft guidance released by the Agency on July 13, 2012, and it replaces and supersedes FDA’s 1999 guidance “Pre-IDE Program and Meetings with Food and Administration Staff: Issues and Answers.” The new guidance includes requirements on the type, timing, format, and content of requests for feedback meetings and telephone conferences with FDA. Therefore, it will be important for the medical device industry to be aware of these requirements in planning their device development activities and timelines.
Q-Sub Organizational Structure
One significant difference between the draft and final guidance documents is that the Agency introduced the concept of the “Q-Submission” (Q-Sub) organizational structure in the final guidance. Q-Subs encompass various types of requests for feedback, including Pre-Submissions, Informational Meetings, Study Risk Determinations, Formal Early Collaboration Meetings (i.e., Agreement and Determination Meetings), Submission Issue Meetings, and Premarket Approval (PMA) Day 100 Meetings. The Agency will refer to these requests for feedback collectively as “Q-Subs,” and the goal for the Q-Sub program is to provide a convenient and effective way to track such requests.
When to Submit a Q-Sub
Q-Subs can be invaluable for early feedback on specific questions during submission preparation, such as in the following circumstances:
However, Q-Subs are not appropriate for any of the following:
Manufacturers may request more than one Q-Sub meeting/teleconference for a device submission. However, the Agency will not grant more than one meeting/teleconference covering the same or similar issues. Thus, it would be appropriate to request a meeting on preclinical studies and, subsequently, a meeting on a clinical study, but it would not be appropriate to request multiple meetings on the iterative versions of the same clinical study.
Q-Subs for Combination Products
FDA’s guidance acknowledges that manufacturers often seek input on issues relating to the device component of a combination product, for example, on devices such as pumps that deliver a drug. Combination product manufacturers should be aware that the new guidance recommends that the Center for Devices and Radiological Health (CDRH) staff notify the lead center for the combination product whenever it receives a Q-Sub and that review staff from the other center(s) be involved to ensure that the entire review team is aware of the questions raised and the responses provided.
Reliability of Agency Feedback
FDA intends that its feedback in response to a Q-Sub will not change, provided that the information submitted in support of the Q-Sub remains accurate. The Agency intends to limit modifications to its feedback to those situations where the initial feedback does not address important new issues relevant to a determination of safety or effectiveness that emerge after the Q-Sub is submitted. However, FDA recommends that sponsors contact the review branch to confirm the feedback guidance if more than one year has passed since the last feedback on key clinical trial design elements. An additional Q-Sub is not required to obtain such confirmation; the confirmation may be obtained through a phone call with the review branch.
Timeframes for Requested Feedback
FDA has established new procedures and timelines for Q-Subs that could significantly impact a device company’s timelines for bringing a device to market. For example, many device stakeholders have found that it is increasingly important to obtain FDA feedback prior to conducting a clinical study on a novel device or a novel modification to an existing device. Because the costs of designing and conducting a clinical study have increased substantially in recent years, companies often seek to avoid the risk of undertaking a study that FDA might later determine is not adequate to support the proposed intended use or marketing claims. Now, for those companies that wish to avoid such risk by obtaining FDA feedback prior to conducting a clinical study, it will be necessary to build into the development plan adequate time to request and obtain such feedback.
In the Guidance, the Agency specifically addresses the timeframes within which FDA intends to provide the requested feedback. Significantly, however, the timeframes provided in the Guidance do not begin until the Q-Sub is deemed “accepted.” In a process similar to that adopted for 510(k) and PMA submissions, during the first 14 days after a request is submitted to FDA, Agency staff will review the submission to determine whether it (1) includes a valid eCopy, (2) meets the definition of the identified Q-Sub type, and (3) is administratively complete. If the submission is not complete, FDA will inform the applicant that it is not accepted and will identify the reasons for not accepting it. The following chart, provided by the Agency in the Guidance, sets forth the timeframes for meetings/teleconferences for each Q-Sub type and indicates whether a meeting is available as an avenue of receiving feedback from FDA.
Q-Sub Type |
Meeting as Method of Feedback? |
Timeframe for Meeting/Teleconference |
Pre-Submission* |
Upon request |
75–90 days** |
Informational Meeting |
Yes |
90 days |
Study Risk Determination |
No |
N/A |
Agreement Meeting |
Yes |
30 days or within timeframe agreed to with sponsor |
Determination Meeting |
Yes |
Date for meeting agreed upon within 30 days of request |
Submission Issue Meeting |
Yes |
21 days |
PMA Day 100 Meeting |
Yes |
100 days (from PMA filing date) |
*As defined in MDUFA III Commitment Letter |
We recommend that companies use the Acceptance Checklist in Appendix 2 of the Guidance prior to submission to ensure all of the required criteria are explicitly addressed.