Modular Submissions for Premarket Approval Applications and Humanitarian Device Exemptions

What You Need to Know? 👇

What is the minimum time interval required between modular PMA submissions?

Modules should be submitted at minimum 90-day intervals to allow FDA sufficient time to review each module and provide feedback before receiving the next submission. The exception is the manufacturing module, which may be reviewed concurrently with other modules if resources permit.

When is the user fee due for a modular PMA application?

The user fee for a modular PMA is due upon submission of the first module. If FDA receives the first module before payment, it will not be accepted for review until payment is received and FDA will notify the applicant by email.

Can I modify my accepted shell after formal submission to FDA?

Yes, changes to timing or module order can be made after receiving review team concurrence via email. For significant changes to content, module titles, or number of modules, you must formally submit a revised shell as an amendment following the same process as the original shell.

What happens if my device design changes after a module is accepted?

If you modify your device after FDA determines a module is acceptable, contact the review staff to discuss the modification. If it’s considered a major change, submit an amendment to affected modules with revised executive summary, change description, and supporting data.

Are modular HDEs subject to user fees like modular PMAs?

No, modular HDEs are not subject to user fees, similar to traditional HDEs. Only modular PMAs require user fee payment upon submission of the first module.

What review phases apply when the final module is submitted?

Upon receiving the final module, FDA converts the modular application into an original PMA or HDE. The application then undergoes standard RTA (Ready-to-Accept) and RTF (Ready-to-File) review phases before substantive review begins, just like traditional applications.

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What You Need to Do 👇

Recommended Actions

1. Contact appropriate FDA review division to discuss intent to submit modular PMA/HDE
2. Prepare and submit shell proposal including:
   • Content description for each module
   • Timeline for module submissions
   • Device description and principles of operation
3. Wait for FDA acceptance of shell before submitting modules
4. Submit modules according to agreed timeline with:
   • Cover letter referencing shell number
   • Table of contents
   • Executive summary
   • Complete test data and results
   • Relevant references
5. Address any deficiencies identified during module reviews
6. Submit final module including:
   • Clinical data
   • Proposed labeling
   • SSED/SSPB
   • Responses to any outstanding deficiencies
7. Monitor and maintain communication with FDA review team throughout process
8. Be prepared to submit amendments if device changes impact previously reviewed modules

Key Considerations

Clinical testing

• Clinical data should typically be submitted in the final module
• Clinical trial period and product development timeline should be carefully considered when planning module submissions
• BIMO information can be submitted as separate module or with clinical module

Non-clinical testing

• Complete all testing needed to support a specific module before submission
• Non-clinical data can be grouped by disciplines (e.g., biocompatibility, engineering bench testing)
• Results and analysis must be included for review

Software

• Software validation and verification information should be included in appropriate module
• Can be grouped with engineering/bench testing module

Labelling

• Proposed labeling including physician instructions, patient instructions, operation manuals to be included in final module
• Post-marketing plan should be included if appropriate

Biocompatibility

• Biocompatibility/toxicity testing can be grouped in dedicated module
• Complete testing results must be provided

Safety

• Summary of Safety and Effectiveness Data (SSED) for PMAs or Summary of Safety and Probable Benefit (SSPB) for HDEs required in final module
• Safety information should be included across relevant modules

Other considerations

• Manufacturing information should be submitted as separate standalone module
• Modules should be submitted at minimum 90 days apart
• Shell must be approved before module submissions
• User fees for modular PMAs due with first module submission
• Interactive review process between FDA and applicant
• Changes to device design may require reopening of closed modules

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Relevant Guidances 🔗

• FDA Actions on Premarket Approval Applications (PMAs) and Effects on MDUFA Review Goals and Timelines
• Quality System Information Requirements for Premarket Submissions
• Manufacturing Site Inspections and PMA Review Process for Medical Devices
• Acceptance and Filing Reviews for Premarket Approval Applications (PMAs)
• User Fees and Refunds for Premarket Approval Applications and Biologics License Applications
• Humanitarian Device Exemption (HDE) Program: Operational Requirements and Benefit-Risk Assessment

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Original guidance

• Modular Submissions for Premarket Approval Applications and Humanitarian Device Exemptions
• HTML / PDF
• Issue date: 2025-01-13
• Last changed date: 2025-01-13
• Status: FINAL
• Official FDA topics: Medical Devices, Premarket
• ReguVirta ID: 9d2d6828eec1089e5cdd8074645b1e7c