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Updated June 6, 2024

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. A physician wishing to use a Humanitarian Use Device (HUD) must submit the IRB form entitled Humanitarian Use Device for Treatment or Diagnosis located in the IRBNet library. This form should describe the physician's interest in using the device and the instances in which it will be used, specifying that the intended use is within the scope of the Humanitarian Device Exemption (HDE).

As the use of an HUD for its approved indication 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. The IRB requires informed consent or use of a modified clinical consent or operative permit that is consistent with the approved labeling. FDA regulations do not require informed consent from patients for the use of a HUD. 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.

In the rare case that no information packet is available, the IRB will request a patient information sheet or informed consent form with the following:

• 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.

FDA regulations at 21 CFR 814, Subpart H describe requirements by which manufacturers may ship medical devices, designated as humanitarian-use devices (HUD), when the intended use is 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. It is the responsibility of the HDE holder to monitor the number of uses per year of an HUD, and if that number exceeds 8,000, to provide an explanation and estimate of how the device is being used.

An HDE is a premarket approval application submitted to FDA in which an individual or sponsor seeks a HDE from the effectiveness requirements of sections 514 and 515 of Chapter V of the Food, Drug, and Cosmetics Act. HDE approval is conferred when the FDA determines:

• the HUD will not expose patients to an unreasonable or significant risk of illness or injury;
• the probable health benefit from use of the device outweighs the risk of injury/illness from its use, with consideration for the risks and benefits of currently available devices or alternative forms of treatment;
• the device would not be available to a person with the disease or illness in question without the HDE approval; and
• there is no comparable device, other than another device approved under an HDE or Investigational Device Exemption (IDE), available to treat or diagnose the disease or condition.

This policy addresses only those FDA regulations that are relevant to investigators and IRB review of HUDs. It is not a comprehensive review of regulations for HUD. Individuals interested in processes for designating HUDs and submission and review of Humanitarian Device Exemption (HDE) applications are advised to review the complete §814, Subpart H. Additional information about HUDs may be found in the FDA guidance: Humanitarian Device Exemption (HDE) Program Guidance for Industry and Food and Drug Administration Staff – issued September 6, 2019. Non-HUD uses of these devices requires a Premarket Approval Application (PMA) (see §814 Subparts A, B, C, D, and E for information about PMAs).

Submission Requirements for Clinical Use of HUD

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 a 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 same
• Add study materials: assessment instruments, surveys, questionnaires, data collection logs, procedural protocols.
• A summary of how the physician proposes to use the device, including a description of any screening procedures, the HUD procedure, and any patient follow-up visits, tests or procedures
• 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

Although not an FDA requirement, the University IRB requires physicians to obtain informed consent from the patient or the patient's legally authorized representative. Before use of an HUD, patients must be informed of the following:

• risks and potential benefits of the HUD,
• procedures associated with the use of the device, and
• a statement that the device is a humanitarian use device for which effectiveness for the labeled indication has not been demonstrated.

IRB Review and Approval for Clinical Use of HUD

Use of 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.

The IRB will not approve uses that exceed the scope of the FDA-approved indications (as evidenced in the HDE Approval Order or other documentation from FDA).

The University IRB may limit the scope of the FDA-approved indications or impose additional restrictions.

Following IRB approval of an HUD, the University IRB does not require review of each individual use providing the use is consistent with the FDA-approved indications and any additional IRB restrictions.

Continuing review must be completed at least annually for clinical uses of HUD. The FDA permits continuing reviews under expedited review procedures as long as no unanticipated problems occur during the review period.

Submission Requirements for annual renewal of Clinical Use of HUD

Physicians must complete the following steps for IRB review and approval of each new project involving a HUD:

• Create a New Package in IRBNet
• Add the Continuing Review - Progress Report Request form
• Add the most recent manufacturer annual Medical Device Report to FDA
• Sign the submission
• Submit for review

IRB determinations for initial and continuing reviews of HUD use are made available to the submitting physician as published Board Documents in IRBNet. Continuing review may be conducted using expedited procedures.

Physician Reporting Requirements for Clinical Use of HUD

Within five days of learning about FDA actions (e.g., FDA-approved amendments to the HDE; changes to the FDA-approved indications; or amended product labeling, clinical or patient brochure) physicians must report the action/changes to the IRB.

Physicians must inform the IRB and FDA as soon as possible but no more than 10 days after receiving information that reasonably suggests a device with an approved HDE under her or his use (or a similar device marketed by the manufacturer or importer) may have caused or contributed to a death or serious injury or has malfunctioned; or would be likely to cause or contribute to a death or serious injury if the malfunction were to recur.

At continuing review (at least annually), physicians must report the number of HUD uses that fall within the FDA-approved indications and IRB limitations (if applicable).

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, a 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, including the applicant’s clinical experience with the device and the number of devices shipped or sold in the United States.

• the identification of the patient involved;
• the date of the HUD use; and
• the reason for the HUD use

Off-Label Use of an HUD

A physician may make Compassionate Use of a HUD for a use other than the FDA-approved indication in a non-emergency situation, if (a) there is no generally acceptable alternative device for treating the patient; and (b) the physician notifies the IRB of the use BEFORE it occurs and obtains IRB approval for the use.

BEFORE using the HUD, the physician using the HUD should:

1. Provide the IRB with notification of the planned use, identify of patient in whom HUD will be used, reasons necessitating use, and plan for monitoring the patient,
2. Obtain IRB approval. Obtain treatment informed consent from the patient,
3. Provide the patient with any HUD patient information packet before the use of the device.
4. Provide the patient with an information sheet describing a general definition of the FDA’s HDE program, a brief description of the device and related procedures, risk/benefit ratio, and physician contact information if the patient experiences a device related adverse event.
5. Develop a schedule to monitor the patient, taking into consideration the patient’s needs and limited information available about the HUD’s risks and benefits.

AFTER the Compassionate Use has occurred, the physician should provide a follow-up report to the IRB within 5 business days of the use. The report should include a description of patient outcome. This report also should be provided to the HDE holder. The physician also should monitor the patient according to the monitoring schedule to detect any possible problems arising from the use of the device.

Investigational Use of HUD

In addition to the clinical use described above, an HDE holder may collect safety and effectiveness data for the HDE-approved indications. If the 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. FDA considers such uses to constitute clinical investigations. It is not needed to make the SR/NSR determination (i.e., FDA had already determined the device was a SR device). However, if a sponsor seeks IRB approval for investigational use of a HUD for an indication other than its approved indication(s) without first obtaining a determination from FDA regarding whether the study is a SR or NSR study, then the IRB should make the SR/NSR determination as required in 21 CFR 812.66.

• If the HUD is being used as approved in the HDE and device labeling, and the HUD is not a significant risk device, the investigation is not subject to requirement for an IDE because the HUD is a legally marketed device (under the HDE).
• If the uses of the HUD are outside of the HDE-approved indications or approved labeling, or the HUD is a significant risk device, an IDE is required.

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).

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