Humanitarian Device Exemption (HDE)
The Humanitarian Device Exemption (HDE) is an approval pathway under FD&C Act § 520(m) [21 U.S.C. § 360j(m)] and 21 CFR Part 814 Subpart H for devices intended to benefit patients with diseases or conditions that affect ≤ 8,000 individuals per year in the USA.
Two-step process
Step 1 — HUD Designation (from OOPD)
Before submitting an HDE application to CDRH, the device must receive Humanitarian Use Device (HUD) Designation from FDA's Office of Orphan Products Development (OOPD):
- Submit a HUD designation request to OOPD with: device description, intended use, scientific rationale for the ≤8,000 patient estimate
- OOPD reviews and responds within 90 days
- The HUD designation letter is included in the HDE application
Step 2 — HDE Application (to CDRH)
Once designated, submit an HDE application to CDRH. Unlike PMA, the HDE uses a "probable benefit" standard — not "reasonable assurance of effectiveness."
HDE vs PMA — effectiveness standard
| Feature | HDE | PMA |
|---|---|---|
| Patient population | ≤ 8,000/year in USA | Any size |
| Effectiveness standard | Probable benefit (lower standard) | Valid scientific evidence (full standard) |
| Clinical data | Encouraged but not always required | Usually required (IDE study) |
| Advisory panel | Less common | Common for novel devices |
| Review time goal | 180 days | 180 days |
| Application fee | Reduced (~$20K vs ~$430K) | Standard |
HDE application contents
An HDE application (21 CFR § 814.102) must include:
- HUD designation letter from OOPD
- Device description and indications for use
- Contraindications, warnings, precautions
- Non-clinical and available clinical data
- Risk-benefit analysis demonstrating probable benefit
- Manufacturing information
- Proposed labelling
- Truthful and accurate statement
Post-approval conditions
Profit restriction
HDE holders may not generate profit from the device unless:
- The device is intended for use in paediatric patients (profit is permitted without IRB approval)
- An IRB has approved the use of the device for profit
Annual reporting
HDE holders must submit annual reports to FDA with updated safety information, device distribution data, and any new studies.
Device tracking
Devices approved under HDE that are implantable must comply with device tracking requirements.