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

What You Need to Know? 👇

What is the difference between HDE and PMA approval pathways for medical devices?

HDE (Humanitarian Device Exemption) is for devices treating rare conditions affecting ≤8,000 patients annually and is exempt from effectiveness requirements. PMA requires demonstrating reasonable assurance of safety and effectiveness for broader populations.

Can medical device companies make profit from HUD sales under an HDE?

Yes, but only if the device meets specific eligibility criteria (pediatric use or development in pediatrics is impossible/unsafe) and sales don’t exceed the Annual Distribution Number (ADN) calculated as devices needed for 8,000 patients.

What is required for IRB approval of HUD use in clinical care?

IRBs or appropriate local committees must approve HUD use at facilities before clinical care (except emergencies). They review HDE approval orders, labeling, and proposed use but don’t need to approve each individual patient use.

How long does FDA take to review HDE applications?

FDA reviews filed HDE applications within 75 days, compared to 180 days for PMAs. If applicants submit major amendments, the review timeframe may extend up to an additional 75 days.

What constitutes “probable benefit” for HDE approval?

Probable benefit exists when evidence reasonably concludes patients are likely to benefit from device use. FDA considers type, magnitude, probability, and duration of benefits, along with patient perspectives and available alternatives.

What post-approval reporting requirements apply to HDE holders?

HDE holders must submit periodic reports including updated population data, comparable device assessments, device distribution numbers, clinical experience summaries, and adverse event reports to both FDA and reviewing IRBs.

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What You Need to Do 👇

Recommended Actions

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

• 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

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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

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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 ID: e4f39ea1f2e0cf3e614cdf469ac48964