Humanitarian Device Exemption (HDE) Postmarket Activities
- Institutional Review Board (IRB) Approval
- IRB Review
- HDE Supplements
- Changes to Indications for Use
- Pediatric HDEs
After HDE approval, a Humanitarian Use Device (HUD) may only be used after IRB approval has been obtained for the use of the device, for the FDA-approved indication, except for an emergency use situation.
An HUD used in a clinical investigation (i.e., to collect safety and probable effectiveness data) is considered to be used for “investigational use”, whether or not the device is used for the HDE-approved indication. Such investigational use is subject to the same requirements that apply to all FDA-regulated clinical studies, including 21 CFR Part 50 (Protection of Human Subjects) and 21 CFR Part 56 (Institutional Review Boards). Additionally, if the HUD is being studied for a use other than its approved indication, the IDE regulations in 21 CFR Part 812 apply.
The HDE holder is responsible for ensuring that an HUD approved under an HDE is administered only in facilities associated with an IRB (per 21 CFR 814.124 and Section 520(m)(4) of the FD&C Act (21 U.S.C. 360j(m)(4)) constituted and acting in accordance with the FDA regulation governing IRBs (21 CFR Part 56), including continuing review of use of the device.
Additional information is available in the Guidance for HDE Holders, Institutional Review Boards (IRBs), Clinical Investigators, and FDA Staff - Humanitarian Device Exemption (HDE) Regulation: Questions and Answers.
IRBs are responsible for initial and continuing review of the HUD. Initial review of an HUD must be performed at an IRB’s convened meeting (21 CFR 56.108). The IRB may give blanket approval for the use of a particular HDE device at an institution, or it may give approval on a case-by-case basis.
Modifications that affect the safety and probable benefit of an approved HDE require the FDA’s review and approval of an HDE supplement (21 CFR 814.108).
The type of HDE supplement necessary depends on the evidence needed to demonstrate the safety and probable benefit of the change. Examples of changes include the following:
- Use of different manufacturing or sterilization site
- Changes in the manufacturing process
- Changes in performance or design
- Select changes in labeling
- Changes to a post-approval study plan/protocol
- Change in the trade name of the device
- Request for exemption from the prohibition on profit
A change for a new indication for use of an approved HUD (e.g., for a different disease or condition) requires a new original HDE application and not a supplement (21 CFR 814.110).
As a check on postmarket safety, the Food and Drug Administration Amendments Act of 2007 (FDAAA) required the FDA’s Pediatric Advisory Committee (PAC) to conduct an annual review of HDE approved pediatric devices permitted to make a profit to ensure that the HDE remains appropriate for the pediatric populations. In addition, the PAC conducts an annual review of adverse events for these devices. For further information, please refer to the Pediatric Advisory Committee webpage.