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.
Recommended Actions
- Obtain HUD designation from FDA’s Office of Orphan Products Development before submitting HDE application
- 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
- 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
- Maintain documentation of:
- Facilities using the device
- Correspondence with IRBs/committees
- Device shipments and sales
- Safety and use data
- Submit supplements for changes affecting safety or probable benefit
- 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
- Annual Distribution Number (ADN) limits profit-making
- Pediatric use has special considerations for profit eligibility
- No comparable device can be available (except other HUDs)
- Must maintain records of facilities using device
- Periodic reports required on device use and safety
Relevant Guidances
- Humanitarian Use Device (HUD) Designation Requests: Content and Format
- Design Controls for Medical Device Manufacturers
- Medical Device Reporting (MDR) Requirements and Procedures for Manufacturers
- Applying Human Factors Engineering and Usability Engineering to Medical Devices
Related references and norms
- 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
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