Manufacturing Site Inspections and PMA Review Process for Medical Devices
This guidance explains the administrative process for reviewing manufacturing information and conducting inspections for Premarket Approval Applications (PMAs) and certain PMA supplements. It outlines the sequence of events, timelines, and procedures for FDA's review of manufacturing sections and facility inspections as part of the PMA approval process.
What You Need to Know? 👇
What is the typical timeline for FDA review of PMA manufacturing sections?
FDA aims to complete manufacturing section reviews within 30 calendar days for non-expedited traditional PMAs and 20 calendar days for expedited PMAs. The total cycle time for manufacturing review and inspection is approximately 140 days for non-expedited and 120 days for expedited PMAs.
When does FDA require a preapproval inspection for PMA applications?
FDA determines inspection necessity after reviewing the PMA manufacturing section. Inspections are typically required for original PMAs, panel-track supplements, and 180-day supplements involving manufacturing changes. The decision depends on inspection history, product similarity, and manufacturing operations complexity.
What are the most common delays in PMA manufacturing reviews?
Common delays include incomplete responses to manufacturing deficiency letters, delayed responses to real-time questions during review, and manufacturing facilities not being ready for inspection. Facilities should have completed process validations and successful design transfer before inspection scheduling.
How long does FDA take to complete PMA facility inspections?
Domestic inspections must be completed within 45 calendar days after assignment, while foreign inspections require 60 calendar days. An additional 30 calendar days are allowed for writing and forwarding the establishment inspection report for both domestic and foreign facilities.
What happens if a PMA facility receives an OAI inspection classification?
Official Action Indicated (OAI) results lead to deficiency letters for PMA-specific issues or Warning/Untitled Letters for broader violations. PMA approval is withheld until objectionable conditions are corrected, potentially requiring re-inspection and additional review cycles.
What manufacturing information should be included in PMA submissions?
PMAs must include comprehensive Quality System regulation information per 21 CFR 820. FDA’s guidance “Quality System Information for Certain Premarket Application Reviews” details specific requirements. Manufacturing facilities should be inspection-ready with completed validations and operational processes.
What You Need to Do 👇
Recommended Actions
- Ensure manufacturing facility is ready for inspection at time of PMA filing
- Complete all process validations before inspection
- Successfully transfer design to production before inspection
- Have manufacturing process operational during inspection when possible
- Submit six copies of PMA or three copies of PMA supplement
- Respond promptly to any deficiency letters or real-time communications from FDA
- For foreign facilities, plan for additional time needed for inspection coordination
- Prepare for potential re-inspection if deficiencies are identified
- Maintain clear communication with FDA regarding facility readiness status
- Document and implement corrections for any identified deficiencies promptly
Key Considerations
Other considerations
- Manufacturing facilities must be ready for inspection at the time of PMA filing unless stated otherwise
- All process validations should be completed and design successfully transferred to production before inspection
- Manufacturing process should preferably be in operation during inspection
- Review timelines:
- Non-expedited Traditional PMA: 30 calendar days
- Expedited Traditional PMA: 20 calendar days
- Domestic inspections: 45 calendar days after assignment
- Foreign inspections: 60 calendar days after assignment
- Inspection outcomes can be:
- No Action Indicated (NAI)
- Voluntary Action Indicated (VAI)
- Official Action Indicated (OAI)
Relevant Guidances 🔗
- Quality System Information Requirements for Premarket Submissions
- Manufacturing Site Changes for PMA-Approved Medical Devices: When to Submit a Supplement and Documentation Requirements
- FDA Actions on Premarket Approval Applications (PMAs) and Effects on MDUFA Review Goals and Timelines
- Acceptance and Filing Reviews for Premarket Approval Applications (PMAs)
Related references and norms 📂
- 21 CFR 820: Quality System Regulation
- 21 CFR 814.20(b)(2): PMA submission requirements
- 21 CFR 814.39: PMA supplements requirements