Manufacturing Site Changes for PMA-Approved Medical Devices: When to Submit a Supplement and Documentation Requirements

What You Need to Know? 👇

What constitutes a manufacturing site change requiring a PMA supplement versus a 30-day notice?

A PMA supplement is required when using a different facility not previously approved in the PMA or for different manufacturing activities. A 30-day notice applies when moving between already-approved sites for similar activities or within the same establishment (same FEI).

When does FDA typically conduct preapproval inspections for manufacturing site change supplements?

FDA considers inspection dates, classifications (OAI/VAI/NAI), relevance to moved activities, recall history, and risk levels. Inspections are likely when sites haven’t been inspected recently, had OAI classifications, or involve high-risk manufacturing processes.

What documentation should be included in a manufacturing site change supplement submission?

Key elements include device description, site diagrams, manufacturing flow charts, equipment descriptions, validation protocols, environmental controls, calibration procedures, supplier controls, and acceptance activities. Validation reports should be completed before inspection scheduling.

Do component manufacturing site changes require PMA supplements for finished device manufacturers?

No, component manufacturing site changes don’t require PMA supplements. However, critical components affecting device function require 30-day notices. Finished device manufacturers maintain compliance through purchasing controls and acceptance criteria per QS regulations.

How does FDA define “different facility” versus “same establishment” for site changes?

Different facilities have separate FEI numbers and require supplements. Same establishment means same FEI number where 30-day notices suffice. Moving between buildings within one establishment (same management, same FEI) is considered a manufacturing procedure modification.

What are the timeline requirements for manufacturing site change supplement approvals?

PMA holders must submit 180-day supplements for site changes affecting safety/effectiveness. HDE holders submit 75-day supplements. Implementation cannot begin until FDA approval is received. Validation activities should be completed before inspection scheduling.

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What You Need to Do 👇

Recommended Actions

1. Determine if change requires site change supplement or 30-day notice based on guidance criteria
2. Prepare required documentation package including:
   • Device and site change descriptions
   • Manufacturing diagrams and flows
   • Process validation plans
   • Control procedures
   • Supplier documentation if applicable
3. Assess likelihood of pre-approval inspection based on FDA factors
4. Complete all validation activities before potential inspection
5. Submit appropriate supplement type with complete documentation
6. Wait for FDA approval before implementing site change
7. Maintain compliance with QS regulation requirements throughout process

Key Considerations

Non-clinical testing

• Process validation or revalidation master plan and procedures must be provided
• Validation reports should be submitted when available
• All validation activities should be completed before inspection scheduling

Software

• Validation of software used in production or quality system where applicable must be documented

Safety

• Environmental and contamination control procedures must be provided if conditions could affect device safety
• Inspection, measuring and test equipment calibration procedures must be documented
• Incoming and final acceptance activities procedures must be provided

Other considerations

• Description of device, intended use, and nature of site change required
• Manufacturing site diagrams and flow diagrams needed
• Equipment and process descriptions affected by change
• List of applicable standards
• For new suppliers/contractors:
  • Purchasing control procedures
  • Supplier evaluation process
  • Quality control requirements
  • Change control mechanisms
  • Records maintenance procedures

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Relevant Guidances 🔗

• 30-Day Notice Manufacturing Changes for PMA and HDE Approved Devices
• Quality System Information Requirements for Premarket Submissions
• Manufacturing Site Inspections and PMA Review Process for Medical Devices

Related references and norms 📂

• 21 CFR Part 820: Quality System Regulation
• 21 CFR 814.39: PMA Supplements and Amendments
• 21 CFR 807.3: Establishment Registration and Device Listing

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Original guidance

• Manufacturing Site Changes for PMA-Approved Medical Devices: When to Submit a Supplement and Documentation Requirements
• HTML / PDF
• Issue date: 2018-12-17
• Last changed date: 2020-10-22
• Status: FINAL
• Official FDA topics: Medical Devices, Postmarket, Premarket Approval (PMA), Biologics
• ReguVirta ID: a62ca8e2ed16fcf68dcf26da22be8ab8