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.
Recommended Actions
- Determine if a benefit-risk assessment is needed based on changes in benefits and risks compared to predicate device
- 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
- If assessment not needed:
- Proceed with standard 510(k) submission requirements
- Document rationale for not conducting benefit-risk assessment
- Consider early interaction with FDA through Pre-Submission Program if planning to include patient preference information or healthcare professional perspective data
- Implement appropriate risk mitigation strategies through labeling, training, or other controls
- 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
- Uncertainty in benefit-risk assessment should be evaluated
- Innovative technology may allow greater uncertainty if balanced by other factors
- Patient tolerance for risk and perspective on benefit should be considered
- Postmarket data can provide understanding of risks and benefits
- Risk mitigation strategies should be implemented when appropriate
Relevant Guidances
- Content and Decision-Making Process for 510k Submissions: Determining Substantial Equivalence
- Refuse to Accept Policy for 510k Submissions: Minimum Threshold Requirements for Administrative and Technical Review
- Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program
- MDUFA Performance Goals and Processing of 510k Submissions
- User Fees and Refunds for 510k Submissions
Related references and norms
- 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
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