Use of Published Literature and Previously Submitted Data in PMA Supplements for Class III Medical Devices

What You Need to Know? 👇

What types of published literature can support Class III medical device PMA supplements?

Published literature may support PMA supplements when it provides sufficient detail about device design, clinical protocols, and outcomes. Reports of US marketing experience, foreign clinical trials, and studies by independent investigators are most valuable when they include complete data sets and objective endpoints.

How does FDA avoid duplication of previously submitted data in PMA supplements?

Under 21 CFR 814.39(c), PMA supplements only require information needed to support the specific change. FDA incorporates relevant data from the original PMA without requiring resubmission. Applicants must justify why existing data demonstrates safety and effectiveness for the modified device.

What criteria make published literature sufficient as sole evidence for supplement approval?

Literature is most likely sufficient when it includes multiple studies by different investigators, detailed statistical plans, objective endpoints, consistent findings across studies, and complete patient accounting. High-quality peer review and investigator competence also strengthen the evidence.

When is priority review available for Class III device supplements?

Priority review is granted when FDA determines the supplement would provide significant public health benefits. This expedited process has been available since 1989 and was codified in FDAMA Section 515(d) for PMAs, PDPs, HDEs and their supplements.

What additional data beyond published literature might FDA require for supplements?

FDA may need underlying study protocols, statistical analysis plans, randomization codes, complete patient records, adverse event data, and detailed case reports. Access to raw data increases the likelihood that published reports can support supplement approval.

How do device supplement requirements differ from pharmaceutical supplement requirements?

Devices are more complex in specifications and manufacturing than drugs with known chemical entities. Published literature for devices must provide sufficient detail to establish comparability in design, performance, and manufacture between the studied device and the supplement subject device.

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What You Need to Do 👇

Recommended Actions

1. When using published literature:
   • Ensure sufficient device design/performance details are available
   • Verify comparability between published device and supplement device
   • Obtain underlying data when possible
   • Document multiple independent studies with consistent findings
2. For data requirements:
   • Review existing PMA/PDP/HDE data for relevance
   • Only submit new data necessary to support the change
   • Justify use of previously submitted data
3. For priority review:
   • Determine if the supplement provides significant public health benefits
   • Follow updated CDRH policy for expedited review requirements
4. Maintain detailed documentation of:
   • Clinical protocols and amendments
   • Statistical analysis plans
   • Complete patient accounting
   • Adverse event information

Key Considerations

Clinical testing

• Clinical data detail level should match 21 CFR 814.20(b)(6)(2) requirements including:
  • Number of investigators and subjects
  • Selection/exclusion criteria
  • Safety and effectiveness data
  • Adverse reactions and complications
  • Patient discontinuation and complaints
  • Device failures and replacements
  • Statistical analyses

Safety

• Complete safety information must be provided for all patients who died or discontinued
• Adverse events from literature should be considered alongside original PMA/PDP/HDE adverse events
• New indications may require additional safety assessment if presenting new risks

Other considerations

• Published literature can be used as sole basis for approval if:
  • Multiple studies by different investigators with consistent findings
  • High level of detail in statistical plans and methods
  • Objective endpoints
  • A priori statistical analysis plans
  • Studies conducted by recognized competent investigators
• Previously submitted data can be incorporated without resubmission if relevant
• Additional data requests limited to what’s needed to support the change

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Relevant Guidances 🔗

• Post-Approval Studies for Medical Devices: Protocol Development, Tracking and Reporting Requirements
• Modifications to PMA-Approved Class III Medical Devices: Selecting the Appropriate Regulatory Submission Type
• Real-Time Review Process for Minor Changes to Approved Medical Devices through PMA Supplements
• Quality System Information Requirements for Premarket Submissions
• Manufacturing Site Inspections and PMA Review Process for Medical Devices

Related references and norms 📂

• 21 CFR 814.20: PMA requirements
• 21 CFR 860.7: Valid scientific evidence requirements
• 21 CFR 814.39: PMA supplement requirements

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Original guidance

• Use of Published Literature and Previously Submitted Data in PMA Supplements for Class III Medical Devices
• HTML
• Issue date: 1998-05-19
• Last changed date: 2020-03-18
• Status: FINAL
• Official FDA topics: Medical Devices, Premarket
• ReguVirta ID: 1d6f00c9aac4f855fd693766c251af89