FDA Actions on Premarket Approval Applications (PMAs) and Effects on MDUFA Review Goals and Timelines
This guidance describes the different FDA actions and industry actions that may be taken on premarket approval applications (PMAs), as well as their effects on MDUFA IV (FY 2018-2022) and MDUFA V (FY 2023-2027) review goals and timelines. It covers original PMAs, panel-track supplements, 180-day supplements, and real-time supplements.
What You Need to Know? 👇
What are the different FDA actions that can be taken on a PMA submission?
FDA can issue approval orders, approvable letters, major deficiency letters, not approvable letters, or denial orders. For real-time supplements, major deficiency letters don’t apply. All actions except major deficiency letters are considered MDUFA decisions measured against performance goals.
How does submitting an unsolicited major amendment affect my PMA review timeline?
An unsolicited major amendment extends the FDA decision goal date. If submitted before Substantive Interaction, the goal extends by elapsed FDA days. If submitted after, it extends by 75% of FDA days elapsed since filing.
What is the difference between MDUFA IV and MDUFA V performance goals for PMAs?
MDUFA V (FY 2023-2027) introduces shared outcome Total Time to Decision goals of 290 calendar days for FY 2023-2024 and 285 calendar days for FY 2025-2027. MDUFA IV goals applied to submissions received in FY 2018-2022.
When does FDA issue a major deficiency letter versus a not approvable letter?
Major deficiency letters request significant missing information necessary to complete review. Not approvable letters are issued when FDA believes the application cannot be approved due to significant deficiencies, typically after an inadequate response to a major deficiency letter.
What happens if my PMA receives a Missed MDUFA Decision communication?
For original PMAs and panel-track supplements exceeding the FDA Day goal by 20 calendar days, FDA provides written feedback including major outstanding review topics and estimated completion date, discussed in a meeting or teleconference.
What are the eCopy and eSTAR requirements for PMA submissions?
All PMA submissions require a valid eCopy or electronic submission using eSTAR template when available. The review clock won’t start without confirmation of user fee payment (if applicable) and valid eCopy/eSTAR. This ensures proper processing and distribution.
What You Need to Do 👇
Recommended Actions
- Ensure all PMA submissions include valid eCopy/eSTAR and user fees where applicable
- Plan submission timelines considering:
- 15-day acceptance review
- 45-day filing review
- 90-day Substantive Interaction goal
- MDUFA decision timelines based on submission type
- Prepare for potential FDA actions:
- Approval Order
- Approvable Letter
- Major Deficiency Letter
- Not Approvable Letter
- Denial Order
- Have processes in place to:
- Respond to FDA communications within required timeframes
- Track review clock status
- Submit amendments appropriately (major vs minor)
- Handle interactive review requests efficiently
- Monitor submission status against MDUFA goals and be prepared for additional interactions if goals are missed
- Consider withdrawal implications if unable to respond within 360 days to certain FDA actions
Key Considerations
Other considerations
- All PMA submissions require a valid eCopy or eSubmission (eSTAR when available)
- Most PMA submissions are subject to user fees
- Original PMAs and panel-track supplements undergo acceptance review (15 days) followed by filing review (45 days)
- Substantive Interaction goal of 90 FDA days for 95% of submissions
- MDUFA decision goals:
- 180 FDA days for original PMAs/panel-track supplements without panel (90%)
- 320 FDA days for original PMAs/panel-track supplements with panel (90%)
- 180 FDA days for 180-day supplements (95%)
- 90 FDA days for real-time supplements (95%)
- Total Time to Decision goals:
- FY2023-2024: 290 calendar days average
- FY2025-2027: 285 calendar days average
- FDA will provide Missed MDUFA Decision communication if decision exceeds goal by 20 days
Relevant Guidances 🔗
- Electronic Copy (eCopy) Program for Medical Device Submissions: Technical Standards and Requirements
- Electronic Submission Template And Resource (eSTAR) for De Novo Classification Requests
- Quality System Information Requirements for Premarket Submissions
- Real-Time Review Process for Minor Changes to Approved Medical Devices through PMA Supplements
- Manufacturing Site Inspections and PMA Review Process for Medical Devices
- User Fees and Refunds for Premarket Approval Applications and Biologics License Applications
Related references and norms 📂
- 21 CFR Part 814: Premarket Approval of Medical Devices
- 21 CFR Part 820: Quality System Regulation
Original guidance
- FDA Actions on Premarket Approval Applications (PMAs) and Effects on MDUFA Review Goals and Timelines
- HTML / PDF
- Issue date: 2022-10-03
- Last changed date: 2022-10-06
- Status: FINAL
- Official FDA topics: Medical Devices, Premarket, Premarket Approval (PMA), Biologics
- ReguVirta ID: a8c671efb630be436d86816d375b5071