Post

Humanitarian Device Exemption (HDE) Program: Operational Requirements and Benefit-Risk Assessment

This guidance provides recommendations for industry and FDA staff about the operational aspects of the Humanitarian Device Exemption (HDE) Program, which allows marketing of Humanitarian Use Devices (HUDs) intended to benefit patients with rare diseases/conditions affecting no more than 8,000 individuals in the US per year. It explains FDA's criteria for determining probable benefit and assessing benefit-risk for HDE applications.

  1. Obtain HUD designation from FDA’s Office of Orphan Products Development before submitting HDE application
  2. Prepare comprehensive HDE application including:
    • Device description and manufacturing information
    • Non-clinical and available clinical data demonstrating probable benefit
    • Risk analysis and mitigation strategies
    • Draft labeling with required statements
    • Quality system documentation
  3. Implement systems for:
    • IRB/committee oversight at facilities
    • Adverse event reporting
    • Distribution tracking and ADN compliance
    • Periodic reporting to FDA
    • Post-approval study execution if required
  4. Maintain documentation of:
    • Facilities using the device
    • Correspondence with IRBs/committees
    • Device shipments and sales
    • Safety and use data
  5. Submit supplements for changes affecting safety or probable benefit
  6. Prepare annual reports including:
    • Updated disease/condition prevalence data
    • Distribution numbers
    • Safety information
    • Changes to device/labeling

Key Considerations

Clinical testing

  • Clinical investigations not required to demonstrate effectiveness but must show probable benefit
  • Clinical data should support that probable benefits outweigh risks
  • Post-approval studies may be required
  • IRB or appropriate local committee approval required for clinical use
  • Emergency use allowed without prior IRB approval in certain situations

Non-clinical testing

  • Non-clinical testing (engineering, animal studies, analytical testing, computer modeling) can reduce need for clinical testing
  • Must demonstrate device will not expose patients to unreasonable risk
  • Quality system requirements apply per 21 CFR Part 820

Human Factors

  • Training requirements may be specified for users
  • User qualifications and experience should be considered
  • Human factors data may be needed to demonstrate safe use

Labelling

  • Must include statement that effectiveness has not been demonstrated
  • Must include HUD designation statement
  • Should describe probable benefits and risks
  • Should include appropriate warnings, precautions, contraindications
  • Patient labeling recommended but not required

Safety

  • Must demonstrate device will not expose patients to unreasonable risk
  • Adverse event reporting required per 21 CFR Part 803
  • Risk mitigation strategies should be implemented
  • Post-market surveillance may be required

Other considerations

  • 21 CFR Part 820: Quality System Regulation
  • 21 CFR Part 803: Medical Device Reporting
  • 21 CFR Part 814 Subpart H: Humanitarian Device Exemption
  • 21 CFR Part 56: Institutional Review Boards

Original guidance

  • Humanitarian Device Exemption (HDE) Program: Operational Requirements and Benefit-Risk Assessment
  • HTML / PDF
  • Issue date: 2019-09-06
  • Last changed date: 2019-09-05
  • Status: FINAL
  • Official FDA topics: Medical Devices, Good Clinical Practice (GCP), Premarket Approval (PMA), Premarket, Biologics, HUD/HDE
  • ReguVirta summary file ID: e4f39ea1f2e0cf3e614cdf469ac48964
This post is licensed under CC BY 4.0 by the author.