Modular Submissions for Premarket Approval Applications and Humanitarian Device Exemptions
This guidance outlines procedures for submitting and reviewing modular Premarket Approval Applications (PMAs) and Humanitarian Device Exemptions (HDEs). The modular review approach allows applicants to submit non-clinical data and manufacturing information for review while still collecting clinical data using the final device design. The scope is limited to original PMAs and HDEs, as supplements would rarely be appropriate for modular review.
Recommended Actions
- Contact appropriate FDA review division to discuss intent to submit modular PMA/HDE
- Prepare and submit shell proposal including:
- Content description for each module
- Timeline for module submissions
- Device description and principles of operation
- Wait for FDA acceptance of shell before submitting modules
- Submit modules according to agreed timeline with:
- Cover letter referencing shell number
- Table of contents
- Executive summary
- Complete test data and results
- Relevant references
- Address any deficiencies identified during module reviews
- Submit final module including:
- Clinical data
- Proposed labeling
- SSED/SSPB
- Responses to any outstanding deficiencies
- Monitor and maintain communication with FDA review team throughout process
- 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
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
Original guidance
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