By Elvira Cawthon, EAS Independent Consultant
Premarket submissions for medical devices are costly, time-consuming, and denial of a submission can be devastating. Though the FDA Q-Submission (Q-Sub) Program, designed to minimize risk by enabling Sponsors and Manufacturers the opportunity to attain early formal regulatory feedback from FDA is an option, many don’t understand what it is and whether it applies to their product. However, a Pre-Submission (Pre-Sub) is the most common Q-Submission and a very good option for firms to meet FDA’s criteria. Unsure if a Pre-Sub is applicable to your product or what is involved if it is?
Here are five key considerations:
1. When is a Pre-Submission Indicated?
A Pre-Submission is indicated when FDA feedback prior to an intended premarket submission is desired, particularly when non-clinical and clinical studies are required. It is important to understand that the goal of a Pre-Sub is to submit well-thought-out, researched and complete information, proposed study designs and regulatory strategies for FDA to review and provide feedback. A Pre-Sub is not intended as a general request for information or for FDA to design study protocols or provide information on current research and product development.
2. What Should Be Included in a Pre-Submission?
A Pre-Submission is a formal written request for feedback from FDA and should clearly detail the overall purpose, device details, proposed Indications for use/intended use, relevant regulatory history, and three or four key focused questions directly relevant to the materials submitted, such as those regarding regulatory strategy; indications for use/intended use; clinical study protocol design; labeling; reprocessing, sterilization and shelf-life; benchtop performance testing; biocompatibility; software/firmware documentation; animal and non-clinical study design; proposed human factors engineering processes; and cybersecurity. It is accompanied by a cover letter identifying the submission as a Pre-Submission, containing the applicant’s contact information, and whether an in-person or teleconference meeting is requested along with three proposed dates and times within 60 to 75 days. An eCopy should be included with the submission package sent to the CDRH or CBRH Document Control Center (DCC).
3. I’ve Made My Pre-Submission, Now What?
Once received and accepted by the DCC, your Pre-Sub will be assigned a ’Q-Sub’ tracking number that should be referenced in all related future FDA communications.
If a meeting is requested and can be accommodated by FDA, notification of the scheduled date and time will be sent within 30 days, and FDA’s formal written feedback will be received a few days prior to the meeting. You should provide FDA with the list of meeting attendees and your proposed agenda. If you plan a presentation, it must be submitted electronically to FDA at least two days before the meeting.
4. What Type of Feedback Can I Expect?
FDA will provide you with a written document that specifically and comprehensively addresses the key questions you posed in your submission as well as any other recommendations for protocol modifications identified during the review process. If a follow-up meeting is scheduled, you will have one hour for open discussion and exchange with the FDA review team regarding elements of the Pre-Submission and FDA’s feedback for which you seek clarification or consensus.
One or more of your team members should be designated to take detailed written notes, audio or video recordings are not permissible. It is not appropriate during a Pre-Sub meeting to present and seek feedback on new information or material. Whether or not accompanied by a meeting, FDA’s written comments are thorough and actionable, and FDA will adhere to the recommendations made when reviewing a future related submission provided no significant new information has arisen since the Pre-Sub review that may affect your submission.
5. I’ve Received FDA’s Feedback, Now What?
It is to your benefit to consider FDA’s feedback and incorporate modifications to address the recommendations made during the Pre-Sub review as FDA intends Pre-Sub feedback to remain unchanged, with additional questions only arising during the review of the future submission if new information is presented or available. While you are not obligated to adhere to the outcome of a Pre-Submission, you should be prepared to justify any deviations in a future submission.
If a meeting was held, the submitter must submit draft meeting minutes to FDA as an Amendment within 15 days, including any materials presented during the meeting via eCopy. The meeting minutes should summarize the issues discussed, how each was resolved, agreements, and action items made. Within 30 days, FDA will notify you that they consider the submitted minutes final, or they will e-mail a revised version. The edits may include post-meeting notes to follow up on action items and/or request a Supplement submission to review the agreed-upon modifications.
The FDA Pre-Submission process is voluntary and does not guarantee the success of future related submissions. However, early interaction with FDA on planned studies and the regulatory pathway can improve the quality of subsequent submissions, leading to shortened review times and increased likelihood of market clearance.