FDA Perspective on the Pre- Submission Program: Updates from MDUFA IV Maureen Dreher, PhD Policy Analyst Clinical Trials Program/ Office of Device Evaluation/ CDRH
Agenda Pre-Submission Program background Updates for MDUFA IV Tips for Successful Pre-Submission Packages Alignment with other Q-Sub types 2
Patients are at the Heart of What We Do CDRH Vision: Patients in the U.S. have access to high-quality, safe, and effective medical devices of public health importance first in the world 3
Mechanisms for FDA Feedback: The Q-Submission Program Pre-Sub Written Feedback Pre-Sub Meeting Requests Submission Issue Meetings Informational Meetings Study Risk Determinations PMA 100 Day Meetings Breakthrough Device Designation Request Early Collaboration Meetings Accessory Classification Request Best Resource for policy on Q-Subs: Requests for Feedback on Medical Device Submissions: The Pre- Submission Program and Meetings with Food and Drug Administration Staff : Issued Sept 29, 2017 4
Q-Submission Metrics (CY2017) All Q-Submissions 3,160 Pre-Submissions 2,452 Submission Issue 401 Study Risk Determination 145 Informational Meeting 96 Designation Request for Breakthrough Device PMA Day 100 Meeting 25 41 5
Pre-Submissions (Pre-Subs) Evolved from pre-ides (est. 1995) Now known as the Pre-Submission Program, est. 2013 Still a voluntary program Reflects industry desire to understand FDA s expectations before marketing or IDE submission Guidance The Pre-Submission Program and Meetings with FDA Staff issued Feb 18, 2014 & updated Sept 29, 2017 Program benefits Build relationships and understanding Educate the review team on novel technology Design testing and development plans that will facilitate FDA review Minimize surprises during the review process If FDA feedback is addressed, can result in better quality submissions 6
Definition of a Pre-Sub A formal written request from an applicant for feedback from FDA to be provided in the form of Formal written response with a meeting for discussion Formal written response only When FDA s feedback on specific questions is necessary to guide product development and/or application preparation Request should include specific questions regarding review issues relevant to a planned IDE or marketing application From the Pre-Submission Guidance https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocum ents/ucm311176.pdf 7
A Pre-Sub is: Intended to be specific to the questions posed Our goal is to provide our best advice for your current needs Other deficiencies or concerns noted during review may be shared as part of feedback Generally meant to be a one-time process per topic (i.e., not iterative) Can be utilized at different times and/or for multiple topics for the same device If significant changes are made to submitter s proposal in response to initial FDA feedback, may be appropriate to engage in repeat interaction on the same topic by submitting a Supplement 8
Interactive Review in a Pre-Sub FDA reviewers are encouraged to work interactively with submitters during Pre-Subs Examples of interaction include Meeting scheduling Administrative questions Obtaining clarification on aspects of the submission needed to respond to submitter s questions For example, requesting details of non-clinical test protocol 9
FDA Feedback on a Pre-Sub Feedback represents FDA s best advice based on the information provided FDA intends to stand behind our feedback unless: Information in subsequent submission is not consistent with Pre-Sub Data in the subsequent submission raise important new issues related to safety and effectiveness New issues materially relevant to a determination of safety or effectiveness that have emerged since the time of the Pre-Sub As defined in Q-Sub Guidance and in MDUFA IV Commitment Letter 10
MDUFA IV Commitments for Pre-Subs RTA timeframe Meeting scheduling logistics Written feedback timing RTA Meeting Scheduling Written Feedback Due Performance Goal MDUFA III By Day 14 - MDUFA IV By Day 15 By Day 30 3 business days before meeting The earlier of 5 calendar days before meeting and Day 70 - Written Feedback Date 11
Pre-Submission Process Acceptance Review Meeting Scheduling Submission Review Written Feedback Meeting (if requested) Meeting Minutes (If applicable) Day 1-15 One RTA checklist for meeting requests and written feedback Up to Day 30 Sent by Day 70 or 5 days prior to meeting, which ever is sooner Submitted within 15 days of meeting & reviewed in 30 days 12
Meeting Scheduling If a meeting is desired, submitter should propose 3 possible dates in their Pre-Sub (face-to-face or teleconference) Reviewer confirms one of those dates by Day 15 or suggests alternatives as part of Acceptance Review Schedule meeting by Day 30 Meetings/telecons should generally be limited to 1 hour Longer times can be requested with a rationale (e.g., complex product/issues) and granted if appropriate 13
Reviewing the Submission & Providing Feedback Lead reviewer assembles a team of relevant scientific experts based on feedback requested Some clarification information may be requested interactively via email prior to official written feedback Ensures that relevant feedback is sent Written feedback provided within 70 days or 5 days prior to a meeting (whichever is sooner) Feedback can be: Written responses to submitter s questions FDA identified review issues beyond questions asked Combination of both 14
Meeting Minutes Submitter formally submits draft minutes within 15 days after the meeting as a formal amendment to the Pre-sub FDA committed to reporting on time to receive draft meeting minutes from industry during MDUFA IV FDA review team should review and edit, if necessary, within 30 days after receipt If edits needed, FDA will send back to submitter (via email) After 15 days, FDA-edited version becomes final, unless: Meeting minutes disagreement amendment is received FDA will arrange a teleconference to discuss At conclusion of teleconference, FDA will revise minutes to reflect resolution OR note that the parties agree to disagree Minutes then considered final 15
Tips for Successful Pre-Subs
Write a Clear Cover Letter What type of Pre-Sub is requested? Do you want written feedback only or do you want a meeting? If a meeting, propose three specific meeting dates Specify if this submission is a new request for feedback on same device/ intended use as prior submission? Reference prior Q-Sub number With whom should FDA correspond? 17
Successful Meetings take Planning and Focus Focus the meeting on what you want to get out of it Allow 2/3 of the time for discussion Limit background review to 1/3 Dedicate someone to take minutes 18
Successes & Challenges of Pre-Sub Program Increasing number of Pre-Subs in recent years Reflects interest from industry Strong commitment to program as part of MDUFA IV negotiations Mechanism that fosters collaboration and dialogue to advance device development Lack of clarity on type of Pre-Sub requested Details of the specific questions 19
Other Meetings and Mechanisms for FDA Feedback
Other Q-Submission Types Q-Submission Type Meeting Timeframe for Feedback (from receipt of submission) Pre-Submission Upon request 70 days or 5 days prior to a scheduled meeting, whichever is sooner Informational Meeting Yes 90 days Study Risk Determination No N/A Submission Issue Meeting Yes 21 days Agreement Meeting Yes 30 days or within time frame agreed to with sponsor Determination Meeting Yes Scheduled within 30 days of request PMA Day 100 Meeting Yes 100 days (from filing of PMA) 21
Submission Issue Meetings Meeting/telecon to discuss outstanding review issue in order to move project forward Provide clarification of FDA deficiencies Feedback on proposal to address complex issues Submitter may request a meeting or written feedback without a meeting Related to deficiencies sent by FDA in the following types of letters: IDE letters Marketing submission hold letter (e.g., 510(k) additional information, PMA not approvable letter) 22
Submission Issue Meeting vs Pre-Sub Submission Issue Meeting Usually a meeting request but may request only written feedback Appropriate for Discussing proposals to address outstanding deficiencies for a submission on hold or an IDE letter Shorter timeframe (21 days) Pre-Submission Always includes a formal written response and may include a meeting Appropriate for Device development/ testing proposals for upcoming, planned regulatory submissions Longer timeframe 23
Summary Pre-Submission Program has grown substantially and interest reflected by industry and FDA commitment as part of MDUFA IV We want to address your device development needs FDA is committed to feedback Pre-Subs distinct from but complemented by Submission Issue Meetings 24
If you have questions Division of Industry and Consumer Education (DICE) DICE@fda.hhs.gov 1(800) 638-2041 or (301) 796-7100 Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with FDA Staff Available at: https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guid ancedocuments/ucm311176.pdf Maureen Dreher, Policy Analyst, Clinical Trials Program, Office of Device Evaluation 301-796-2505 Maureen.Dreher@fda.hhs.gov 25