The review process for a Pre-Sub, including timelines outlined in the MDUFA IV Commitment Letter, are described below.

Acceptance Review

Within 15 days of the review clock starting, FDA staff will conduct an acceptance review using the Acceptance Checklist. When completed, the submitter will receive notification regarding whether or not the submission has been accepted for review as well as the contact information for the lead reviewer or the RPM. If a Pre-Sub requesting a meeting is accepted, this notification will also either confirm the submitter’s requested meeting date or provide two alternative meeting dates that are scheduled prior to day 75.

If the acceptance review determines that the request does not qualify as a Pre-Submission or the submission is not complete, FDA staff will obtain concurrence from management of the decision to Refuse to Accept (RTA), and the submitter will receive notification of this decision with the reasons for refusal. The submitter may respond to an RTA notification by submitting additional information to the DCC, which will be logged in as an amendment to the Q-Sub. Upon receipt of the newly submitted information, the review clock will restart at day 0, and FDA staff will conduct the acceptance review again, following the same procedure, within the first 15 days of the restarted review clock. The subsequent acceptance review will assess whether the new information makes the submission complete according to the Acceptance Checklist.

Scheduling of Meeting.

FDA will attempt to schedule a meeting (in person or teleconference) on one of the submitter’s requested meeting dates, if feasible. Meeting dates between 60-75 days following FDA receipt of your submission are most likely to be feasible. If FDA cannot accommodate one of the submitter’s requested dates, FDA will offer at least two alternative dates that are prior to 75 days from the receipt date of an accepted submission. FDA intends to reach agreement with the submitter regarding a meeting date within 30 days from receipt of an accepted submission. For all requests for meetings that do not have an agreed upon meeting date scheduled by 30 days from receipt of an accepted submission, an FDA manager will contact the submitter to resolve scheduling issues by the 40th day.

Feedback.

Written feedback will be provided to the submitter by email or fax and will include: written responses to the submitter questions; FDA’s suggestions for additional topics for the meeting or teleconference, if applicable; or, a combination of both. FDA intends to follow the timeline below for providing feedback to a Pre-Sub.

• Pre-Sub Written Feedback: If no meeting is requested, written feedback will be provided within 70 days of receipt of the accepted submission and will serve as the official record of the Agency’s feedback.
• Pre-Sub Meeting: If a meeting is requested, written feedback will be provided at least 5 days prior to the scheduled meeting, and no later than 70 days from receipt of the accepted Pre-Sub. If all the submitter’s questions are addressed to the submitter’s satisfaction, the submitter may cancel the meeting and the written response will serve as the official record of the Agency’s feedback. If a meeting is held, the meeting minutes along with the written feedback will constitute the official record of the Agency’s feedback.

FDA will generally be unable to review and respond to additional information prepared by the submitter and provided to FDA between receiving FDA written feedback and holding the meeting or during the meeting. Any information that necessitates additional FDA review should be submitted as a supplement to the Pre-Sub. It is, however, appropriate to narrow your agenda to focus on specific questions or topics in the feedback.

FDA feedback represents the best advice based on the information provided in the PreSub and other information known at that point in time. FDA intends that feedback the Agency provides in response to a Pre-Sub will not change, provided that the information submitted in a future IDE, IND, or marketing submission is consistent with that provided in the Pre-Sub, and that the data in the future submission, changes in the science, or changes in the standards of care do not raise any important new issues materially affecting safety or effectiveness. Modifications to FDA’s feedback will be limited to situations in which FDA concludes that the feedback given previously does not adequately address important new issues that have emerged since the time of the Pre-Sub, and that are materially relevant to a determination of a reasonable assurance of safety and/or effectiveness, substantial equivalence, or other relevant regulatory decision. For example, FDA may modify previous feedback if new scientific findings emerge that indicate there is a new risk or an increased frequency of a known risk that affects prior advice; or if there is a new public health concern that affects prior advice. In such cases, FDA will acknowledge a change in advice, will clearly document the rationale for the change, and the determination will be supported by the appropriate management concurrence, consistent with applicable SOPs. Further, FDA intends to work with the submitter to address any new issues raised by the change, taking into consideration the stage of device development, where possible.

Because clinical practice is constantly evolving, FDA recommends that if more than one (1) year has passed since previous FDA feedback was received (via Q-Sub or other formal feedback methods) on significant study design topics, and the study has not been initiated, submitters should contact the review division to confirm that previous advice is still valid. This can be accomplished through a phone call or email to the lead reviewer or RPM; a new Pre-Sub is not needed.  

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