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Benefit-Risk Assessment with Uncertainty in Medical Device Premarket Submissions

This guidance describes FDA's approach to considering uncertainty in benefit-risk determinations for medical device premarket approval applications (PMAs), De Novo requests, and humanitarian device exemption (HDE) applications. It aims to promote public health by helping patients have timely access to new medical devices while ensuring they meet applicable statutory standards for safety and effectiveness.

  1. Evaluate factors affecting acceptable uncertainty level for your device
  2. Consider if your device qualifies for greater uncertainty acceptance (breakthrough or small population)
  3. Design appropriate premarket clinical studies based on acceptable uncertainty level
  4. Develop robust postmarket data collection plan if needed
  5. Prepare labeling that appropriately communicates uncertainty and postmarket data collection
  6. Consider using real-world data sources for postmarket evidence generation
  7. Engage early with FDA through Q-submission process to discuss development program
  8. Document benefit-risk assessment considering all relevant factors
  9. Plan for timely postmarket data collection if required
  10. Prepare for potential advisory committee review of postmarket data

Key Considerations

Clinical testing

  • Clinical evidence requirements are flexible and tailored to the device
  • Greater uncertainty may be accepted for breakthrough devices and devices for small populations
  • Postmarket data collection may be required to address uncertainty
  • Sample size requirements may vary based on accepted level of uncertainty

Non-clinical testing

  • Non-clinical performance data can provide essential information on safety and effectiveness
  • Can inform clinical trial design and extent of premarket evidence needed
  • Can include bench studies, animal studies, and computational modeling

Labelling

  • May need to include information about postmarket data collection and its purpose
  • Should be updated when additional postmarket data supports changes

Safety

  • Must demonstrate reasonable assurance of safety
  • Risk mitigation measures should be considered
  • Uncertainty in safety profile must be balanced against benefits

Other considerations

  • 21 CFR 860.7: Determination of Safety and Effectiveness
  • 21 CFR 814.82: Postapproval Requirements

Original guidance

  • Benefit-Risk Assessment with Uncertainty in Medical Device Premarket Submissions
  • HTML / PDF
  • Issue date: 2019-08-30
  • Last changed date: 2019-08-29
  • Status: FINAL
  • Official FDA topics: Medical Devices, HUD/HDE, Postmarket, Premarket Approval (PMA)
  • ReguVirta summary file ID: fee4a4a4249ff40d47e9073d893f3266
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