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Benefit-Risk Factors to Consider When Evaluating Substantial Equivalence in 510k Submissions

This guidance helps 510(k) submitters demonstrate substantial equivalence when there are differences in technological characteristics between a new device and its predicate device. It specifically focuses on situations where there is either 1) an increase in risk and increase/equivalent benefit or 2) a decrease in benefit and decrease/equivalent risk when comparing the new device to the predicate device.

  1. Determine if a benefit-risk assessment is needed based on changes in benefits and risks compared to predicate device
  2. If assessment needed:
    • Document technological differences and their impact on benefit-risk profile
    • Provide appropriate performance data (clinical and/or non-clinical)
    • Evaluate severity and probability of risks
    • Assess magnitude and probability of benefits
    • Consider additional factors like uncertainty and risk mitigation
    • Include benefit-risk assessment summary in 510(k) summary
  3. If assessment not needed:
    • Proceed with standard 510(k) submission requirements
    • Document rationale for not conducting benefit-risk assessment
  4. Consider early interaction with FDA through Pre-Submission Program if planning to include patient preference information or healthcare professional perspective data
  5. Implement appropriate risk mitigation strategies through labeling, training, or other controls
  6. Monitor postmarket data to confirm benefit-risk profile understanding

Key Considerations

Clinical testing

  • Clinical data is not typically included in 510(k)s but may be warranted in some cases
  • When clinical data is needed, it should include valid scientific evidence from well-designed studies
  • Clinical studies should be adequately designed to avoid uncertainty in benefit-risk assessment

Non-clinical testing

  • Can include performance testing, reliability testing, human factors testing, mechanical testing, animal studies, cell-based studies, computer simulations
  • Should characterize properties like precision, reproducibility, wear, strength, biocompatibility, EMC, sterility
  • Valid scientific evidence from non-clinical testing can support benefit-risk assessment

Human Factors

  • User interface evaluations may be needed to assess device performance and risks
  • Should consider benefits for healthcare professionals and caregivers in terms of device usability
  • Training requirements should be evaluated as risk mitigation

Labelling

  • Should include appropriate warnings, precautions, contraindications
  • Can be used as risk mitigation measure
  • Should identify proper device usage instructions

Safety

  • Severity, types, number and rates of harmful events should be assessed
  • Probability of harmful events should be evaluated
  • Duration of harmful events should be considered
  • Device-related serious and non-serious adverse events should be analyzed
  • Procedure-related complications should be evaluated

Other considerations

  • 21 CFR 803.3: Medical Device Reporting
  • 21 CFR 860.7: Determination of Safety and Effectiveness
  • 21 CFR 807.92: Content and Format of 510(k) Summary

Original guidance

  • Benefit-Risk Factors to Consider When Evaluating Substantial Equivalence in 510k Submissions
  • HTML / PDF
  • Issue date: 2018-09-25
  • Last changed date: 2020-10-20
  • Status: FINAL
  • Official FDA topics: Medical Devices, 510(k), Biologics
  • ReguVirta summary file ID: b03b50d93cdeb0e3069b2cd9f1713610
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