125. Humanitarian Use Devices
Updated August 31, 2026
The University supports the clinical use of humanitarian-use devices (HUDs). An HUD is intended to benefit patients in the treatment and diagnosis of diseases or conditions that affect or are manifested in fewer than 8,000 individuals in the US per year. An HUD is approved for marketing through an HDE application. An HDE application is a Pre-Marketing Approval application that is not required to contain clinical data demonstrating "effectiveness'' (as defined under (21 CFR 860.7 (e)(1).) The FDA may grant HUD designation to a device which meets the criteria in 21 CFR 814.102, and marketing approval for an HUD device through a Humanitarian Device Exemption (HDE). Only HUDs with approved HDEs may be used. A physician must apply for and receive IRB approval before an HUD may be used, either under a protocol for blanket use at the institution or on a case-by-case basis. As the use of an HUD for clinical care is not considered "research", the IRB's requirement for education in the protection of participants, as well as the requirement for independent scientific review of the protocol and for the use of a research-specific HIPAA authorization form, are waived.
Note that IRB approval of the HUD is limited to both the institution and the clinician(s) listed within the HUD application. If a new clinician would like access to the HUD for clinical use, an amendment to the HUD application would need to be submitted for review and approval by the IRB. In emergency situations where the clinician is unable to obtain approval by the IRB to be added to the HUD application, they would follow the emergency use of an HUD reporting requirements, and then submit an amendment.
FDA regulations do not require informed consent from patients for the use of an HUD when the HUD is used according to the marketed HDE indications. Most HDE holders develop patient information packets that generally contain a discussion of the potential risks and benefits of the HUD and any procedures associated with its use. If a patient information packet is not available from the HDE holder, or if the IRB approval includes off-label treatment use of the HUD, the IRB will request an IRB approved patient information sheet or informed consent form with the following content:
- An explanation that the HUD is designed to diagnose or treat the disease or condition described in the HDE labeling and that no comparable device is available to treat the disease or condition;
- A description of any ancillary procedures associated with the use of the HUD;
- A description of the use of the HUD;
- All known risks or discomforts; and an explanation of the postulated mechanism of action of the HUD in relation to the disease or condition;
- Information reflecting the HUD status of the device, such as a sentence indicating that the effectiveness of this device for this use has not been demonstrated.
- If the HUD is being used off-label provide the rational for its use off-label
Note, investigational use of a Humanitarian Use Device (i.e., to establish safety and effectiveness of the device, regardless of whether it is being used in accordance with its Humanitarian Device Exemption) needs to meet the requirements of all relevant IRB policies governing human research and must comply with 21 CFR 812. See the section on Investigational Use of HUD for more information.
Off-Label Clinical Use of an HUD
The University IRB may approve off-label treatment use of the HUD within the HUD application. In such cases, the physician must use an IRB approved patient information sheet or informed consent as noted above and implement a reasonable plan to monitor the patient following use of the HUD. In the event that off-label use was not identified as a possible need at the time of initial approval, and such use is emergent, physicians must follow the procedures outlined in the Emergency Use section of this policy.
Emergency Use of an HUD
If a physician determines that IRB approval cannot be obtained in an emergency situation in time to prevent serious harm or death to a patient, an HUD may be used without prior IRB approval providing that, within five days of the emergency use, the physician provides written notification to the IRB Chair with the following information: identification of the patient involved (age and sex of the patient), the date of the use, and the reason for the use. The physician should submit a follow-up report on the patient’s condition to the HDE holder. The HDE holder is required under 21 CFR 814.126(b) to submit periodic reports to the FDA, including the applicant’s clinical experience with the device and the number of devices shipped or sold in the United States.
IRB Review and Approval for Clinical Use of HUD
Use of an HUD in accordance with the terms of the approved HDE and device labeling is not considered to be research as defined by the FDA; this use is considered clinical use of an approved device. Clinical uses of HUDs are initially reviewed and approved by the convened IRB.
When reviewing an application for use of an HUD, the University IRB will ensure IRB members or consultants have the appropriate experience and expertise for a complete and adequate review of the use of the HUD at the University/Affiliate site. In the absence of this expertise, the IRB may enter into an agreement with a similarly constituted IRB for oversight of the use of the HUD.
Following IRB approval of an HUD, the University IRB does not require review of each individual use providing the use is consistent with the uses approved in the HUD application.
Continuing review must be completed at least annually for clinical uses of the HUD. The FDA permits continuing reviews under expedited review procedures as long as no unanticipated problems occur during the review period and the use of the HUD is within the indications listed in the HDE. In cases in which the University IRB’s approval for use of the HUD includes off-label indications, and such off-label clinical uses have occurred during the continuing review period, continuing review will be conducted by the convened Board.
All adverse events, whether expected or not, that reasonably suggest that an HUD may have caused or contributed to serious injury, death, or malfunction at the facility overseen by the University IRB must be reported to both the FDA and the IRB per policy 730 Unanticipated Problems Involving Risks to Participants or Others.
Any FDA approved amendments to the HDE that impact the indications of the HUD or supplemental materials (e.g., product labeling, patient information packet, manufacturer’s requirements for practitioner training, etc.) must be submitted for IRB review and approval prior to use. Any amendments considered minor modifications may be reviewed through expedited procedures. Any significant changes (i.e. new indications, new clinical providers, etc.) must be reviewed by the convened Board.
IRB determinations for initial review, amendments, and continuing reviews of the HUD use are made available to the submitting physician as published Board Documents in IRBNet.
Submission Requirements for Clinical Use of HUD
The University IRB will follow the review criteria in 21 CFR 56.111 and elsewhere in part 56, where applicable. Physicians must complete the following steps for IRB review and approval of each new project involving an HUD:
- Create a New Project in IRBNet
- Add Part I, Cover Sheet
- Add Humanitarian Use Device Application (available from the researcher library in IRBNet)
- Add FDA HDE Approval Order
- Add documentation of approval from the physician's institution/business for use of the HUD
- Add product labeling
- Add the patient information packet that will accompany the HUD
- Add device manufacturer's requirements/recommendations for practitioner training and qualifications for implementation of the device, and documentation from practitioner that she/he meets them
- Add as applicable, a sample consent form for the use of the HUD in clinical care
- Share IRBNet access for all study personnel and the Responsible Official
- Provide her/his electronic signature through IRBNet
- Submit the project for Full Committee Review
Submission Requirements for Annual Continuing Review of Clinical Use of HUD
Physicians must complete the following steps for IRB review and approval of each new project involving an HUD:
- Create a New Package in IRBNet
- Add the HUD Continuing Review form
- Add the most recent manufacturer annual safety report to FDA.
- Add as applicable, any previously unsubmitted Medical Device Report.
- Add as applicable, any new relevant information or materials.
- Sign the submission
- Submit for review
Investigational Use of HUD
In addition to the clinical use described above, an HDE holder may choose to collect safety and effectiveness data. Collecting data on the safety or effectiveness of an HUD constitutes research, and the FDA considers such uses to constitute clinical investigations. When an HUD is studied in a clinical investigation, the elements included in the informed consent document must conform to the requirements found in 21 CFR 50.25. If, in the clinical investigation, the HUD is being used as approved in the HDE and in accordance with device labeling, the investigation is not subject to IDE requirements and the IRB does not need to make a SR/NSR determination. However, for investigational use of an HUD for an indication other than its approved indication(s), the clinical investigation is subject to IDE requirements. In such cases, the IRB should make the SR/NSR determination as required in 21 CFR 812.66 if a sponsor seeks IRB approval without first obtaining a determination from FDA regarding whether the study is a SR or NSR study.
NOTE: University/Affiliate investigators conducting investigational uses of non-significant risk HUDs must comply with the requirements for investigational devices (at §812); IRB review (at §56.111); informed consent (at §50.20); documentation of consent (unless the IRB waives the requirement for participants to sign a written consent form in accordance with regulations at §56.109, item (c)); and reporting unanticipated adverse device effects (at §812.150, item (a)(1).