Acceptance and Filing Reviews for Premarket Approval Applications (PMAs)
This guidance outlines the process and criteria for FDA staff to conduct acceptance and filing reviews of Premarket Approval Applications (PMAs). It applies to original PMAs and panel-track PMA supplements. The guidance aims to ensure consistent and efficient review of PMAs by establishing clear acceptance and filing criteria to determine if an application is administratively complete and contains adequate technical elements for substantive review.
What You Need to Know? 👇
What are the key differences between PMA acceptance and filing reviews?
Acceptance review assesses administrative completeness within 15 days, ensuring all required elements are present. Filing review evaluates basic technical adequacy within 45 days, determining if the application permits substantive review. Both must be completed before FDA begins substantive review.
When does the FDA review clock start for PMA applications?
The FDA review clock begins only after both acceptance and filing decisions are complete. It starts from the date of receipt of the most recent application or amendment that made the PMA complete and enabled FDA’s “Accepted” and “Filed” decisions.
What happens if my PMA receives a “Refuse to Accept” designation?
You can respond by submitting only the missing information identified in the acceptance checklist as an amendment under the original PMA number. No new application or user fee is required. FDA will re-review within 15 days of receiving the additional information.
Are manufacturing sections required for all PMA submissions?
Yes, manufacturing sections are now required for original PMAs and panel-track supplements with new manufacturing sites or substantially different procedures. Previously, delayed submission within 90 days was acceptable, but this is no longer the case due to rare usage.
What constitutes valid scientific evidence for PMA acceptance?
Valid scientific evidence excludes isolated case reports, random experience, reports lacking scientific evaluation details, and unsubstantiated opinions per 21 CFR 860.7. The PMA must contain data beyond these categories to meet acceptance criteria for administrative review.
How should combination products be handled in PMA applications?
Combination products must be identified as such per the 21st Century Cures Act. Device-led combination products containing approved drugs require patent certifications and notices. Products without approved drug constituents should mark relevant sections as “N/A” in the acceptance checklist.
What You Need to Do 👇
Recommended Actions
- Ensure all administrative elements are complete before submission:
- All required sections in English
- Table of contents and bibliography included
- Device description and manufacturing information complete
- Required certifications and statements included
- Verify technical documentation is comprehensive:
- Full non-clinical test reports provided
- Clinical study protocols and results included
- Statistical analyses complete
- Draft labeling prepared
- Address any prior FDA feedback:
- Document prior submissions and interactions
- Address previous safety/effectiveness concerns
- Include responses to Q-submission feedback
- Validate study design and execution:
- Confirm protocol was followed
- Verify final device design was used
- Ensure population matches intended use
- Justify any deviations
- Prepare appropriate justifications:
- For any omitted elements
- For alternative approaches
- For use of foreign clinical data
- For changes in device design
- Review acceptance and filing checklists:
- Use as guide during preparation
- Ensure all criteria are addressed
- Include rationale for any N/A items
Key Considerations
Clinical testing
- Clinical study data must be collected and analyzed per protocol
- Patient population must match intended use
- Endpoints must be clinically relevant
- For OUS studies, data must be applicable to US population
- Final study protocols must be included
- Study population demographics must be provided
- Description of adverse events must be included
- Statistical analyses must be provided
Non-clinical testing
- Full test reports must be provided for:
- Sterilization
- Biological/Microbiological testing
- Immunological testing
- Toxicological/Biocompatibility testing
- Engineering testing
- Chemistry/Analytical testing
- Shelf life testing
- Animal studies
Labeling
- Draft labeling must include:
- Physician labeling with indications, contraindications, warnings, precautions, and instructions
- Patient labeling (if required)
- Technical/Operator’s manual
Biocompatibility
- Included as part of non-clinical testing requirements
- Must provide full test reports for biocompatibility testing
Safety
- Description of adverse events must be provided
- Safety analyses must be included
- Report forms for deaths and discontinuations required
Other considerations
- Manufacturing information required for original PMAs
- Environmental assessment or categorical exclusion required
- Financial disclosure from clinical investigators required
- Pediatric use information required
- For combination products:
- Must identify as combination product
- Patent certifications required if contains approved drug
- Prior submissions must be addressed
- Q-submission interactions must be documented
Relevant Guidances đź”—
- Post-Approval Studies for Medical Devices: Protocol Development, Tracking and Reporting Requirements
- Real-Time Review Process for Minor Changes to Approved Medical Devices through PMA Supplements
- Modifications to PMA-Approved Class III Medical Devices: Selecting the Appropriate Regulatory Submission Type
- Modular Submissions for Premarket Approval Applications and Humanitarian Device Exemptions
- Annual Reports for PMA-Approved Medical Devices: Content, Format and Submission Requirements
- 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 đź“‚
- 21 CFR 814.20: PMA content requirements
- 21 CFR 814.42: PMA filing review requirements
- 21 CFR Part 54: Financial disclosure requirements
- 21 CFR 812.28: Requirements for foreign clinical studies