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

What You Need to Know? 👇

What is the purpose of the FDA’s benefit-risk guidance for 510(k) submissions with different technological characteristics?

This guidance helps manufacturers demonstrate substantial equivalence when their new device has different technological characteristics than the predicate device. It provides a framework for evaluating whether a device is “as safe and effective” as the predicate, particularly when there are trade-offs between benefits and risks.

When should I include a benefit-risk assessment in my 510(k) submission?

A benefit-risk assessment is recommended when comparing your new device to the predicate device shows either: 1) increased risk with increased or equivalent benefit, or 2) decreased benefit with decreased or equivalent risk. It’s not needed when benefits increase while risks decrease or remain equivalent.

What types of performance data can support a benefit-risk assessment in a 510(k)?

Both non-clinical and clinical data can support benefit-risk assessments. Non-clinical data includes performance testing, reliability studies, animal studies, and computer simulations. Clinical data may include controlled studies, case histories, and testing on clinically derived specimens when appropriate for demonstrating substantial equivalence.

How does FDA evaluate the “probability” of benefits and risks in 510(k) reviews?

FDA evaluates “probable” benefits and risks based on valid scientific evidence, not purely theoretical considerations. This includes hypothesis testing, formal probability concepts, and predictive likelihood assessments. The evaluation considers factors like magnitude, duration, patient population affected, and uncertainty levels in the available data.

Can risk mitigation strategies help achieve substantial equivalence when my device has increased risks?

Yes, appropriate risk mitigation can help demonstrate substantial equivalence. Common strategies include labeling revisions (warnings, precautions, contraindications), training requirements, and complementary diagnostic tests. FDA evaluates whether these mitigations adequately address the increased risks compared to the predicate device.

What role does patient preference information play in 510(k) benefit-risk assessments?

Patient preference information (PPI) can inform benefit-risk assessments by providing insights into patient risk tolerance and perspectives on benefits. This includes patients’ willingness to accept higher risks for greater benefits or quality of life improvements. FDA recommends consulting the PPI guidance and engaging early with review divisions.

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What You Need to Do 👇

Recommended Actions

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

• 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

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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
• Q-Submission Program: Strategic Framework for FDA Interactions in Medical Device Development
• 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

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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 ID: b03b50d93cdeb0e3069b2cd9f1713610