HDE

The Humanitarian Device Exemption (HDE) is a unique FDA pathway established under Section 520(m) of the Federal Food, Drug, and Cosmetic Act to encourage the development and availability of devices for rare diseases and conditions. An HDE allows marketing of a Humanitarian Use Device (HUD) that has not been proven effective under the standards required for traditional approval, but demonstrates probable benefit.

Eligibility requirements:

To qualify for HDE consideration, a device must receive HUD designation from FDA, which requires:
- Disease or condition affects fewer than 8,000 individuals per year in the United States
- No comparable device alternative exists for diagnosis, treatment, or mitigation
- Credible evidence that the device will not be available without HDE exemption
- Application for HUD designation submitted before or with HDE application

Examples include devices for rare pediatric conditions, ultra-rare genetic disorders, or specific cancer subtypes with limited patient populations.

Approval requirements:

Unlike traditional Premarket Approval (PMA), HDE approval requires:
- Probable benefit standard (not proven effectiveness) - device must show likely benefits outweigh risks
- Valid scientific evidence demonstrating safety
- Compliance with good manufacturing practices (GMP)
- Labeling must prominently state the device is HDE-approved
- Device must not expose patients to unreasonable or significant risk

Clinical data requirements are less stringent than PMA, often relying on case series, literature, and expert opinion due to difficulty recruiting large patient populations.

Profit restrictions:

Original HDE law prohibited profit from device sales. However, the 21st Century Cures Act (2016) modified profit restrictions:
- Devices for pediatric populations - profit allowed without restrictions
- Adult devices treating/diagnosing diseases affecting ≤8,000 patients - profit allowed if manufacturer obtains annual certification and meets reporting requirements
- Adult devices treating/diagnosing diseases affecting 4,000-8,000 patients - additional requirements apply

Manufacturers must submit annual distribution numbers and financial certification to maintain compliance.

IRB oversight and informed consent:

HDE-approved devices require Institutional Review Board (IRB) approval before use at each facility:
- Initial and continuing IRB review required
- Informed consent must be obtained from patients
- IRB must determine probable benefit outweighs risk for each use
- Emergency use provisions exist when informed consent cannot be obtained

This provides additional patient safeguards and ethical oversight.

Post-market requirements:

HDE holders must:
- Submit annual distribution reports to FDA
- Report adverse events through MDR system
- Update FDA on any new safety information
- Maintain manufacturing compliance
- Renew HDE annually (no fee for renewal)
- Conduct post-approval studies if required by FDA

Recent trends:

FDA has approved over 100 HDE devices since program inception, with increasing approvals for pediatric devices following the 21st Century Cures Act. Recent approvals include devices for pulmonary hypertension in children, rare cardiac conditions, and specific cancer treatments. The pathway continues to evolve as FDA balances access for rare disease patients with safety oversight.