A Humanitarian Use Device (HUD) is a medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals in the United States per year. FDA regulations (21 CFR 814.124) provide for the submission of a Humanitarian Device Exemption (HDE) in which the manufacturer is not required to provide the results of scientifically valid clinical investigations demonstrating that the device is effective for its intended purpose prior to marketing. This regulation was developed to provide an incentive for the development of devices for use in the treatment or diagnosis of diseases affecting these populations.
An HDE is a type of Pre-Market Approval (PMA) that allows the FDA to grant an exemption from the effectiveness requirements of the PMA regulations. Devices approved with an HDE are referred to as a Humanitarian Use Devices (HUD). The provisions for obtaining an HDE are:
- The device is designed to treat or diagnose a disease or condition that affects fewer than 8,000 individuals per year in the U.S.
- The device is not available otherwise, and there is no comparable device available to treat or diagnose the disease or condition; and
- The device will not expose patients to unreasonable or significant risk, and the benefits to health from the use outweigh the risks.
Treatment under an HDE is not considered research, but the FDA requires IRB approval prior to use. The IRB looks at the safety of the device and decides what information patients should receive about the safety and effectiveness of the HUD.
When the manufacturer submits the HDE it must provide sufficient information in order for the FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury to the patient and that the probable benefits to health outweigh the risk of injury or illness from its use.
A Humanitarian Device Exemption (HDE) application is similar to a premarket approval (PMA) application. However, due to the limited size of the target population and the impracticability of conducting clinical trials to establish safety and effectiveness, an HDE is exempt from the requirement to establish reasonable assurance of effectiveness. The FDA's approval is based its determination that the device will not expose patients to an unreasonable risk of injury or illness and the "probable benefit" to health. This is a considerably lower standard than proof of safety and effectiveness.
FDA approval of an HDE authorizes an applicant to market the HUD, subject to certain profit and use restrictions. HUDs cannot be sold for profit, except in very limited circumstances. Most importantly, they can only be used in a facility after an IRB has approved their use in that facility, except in certain emergencies.
How is an HDE different from an IDE?
An IDE is an exemption that allows a sponsor to ship an investigational device prior to marketing approval; it authorizes the investigational use of the device. A HUD with an approved HDE is approved for marketing. This means that the sponsor can ship the device and can bill for its use (but cannot make a profit from its sale except under limited circumstances). To receive approval for an HDE, the FDA must conclude that there is no comparable device available to treat the disease or condition. If a comparable device is approved by the FDA, the HDE approval may be withdrawn. An HDE therefore is analogous to a PMA application; it’s an application to market the device. An IDE is an application to ship an investigational device to conduct studies.
To approve a PMA device, the sponsor has to provide data from adequate and well-controlled trials that provide substantial evidence of effectiveness (and safety). The requirements for approval of an HDE application to market a HUD are quite a bit lower. FDA's Q&A states that an approved HDE represents "a determination by FDA that the HUD will not expose patients to an unreasonable or significant risk of illness or injury and the probable benefit to health from use of the device outweighs the risk of injury or illness from its use while taking into account the probable risks and benefits of currently available devices or alternative forms of treatment."
What are the IRB's Responsibilities for a HUD?
Generally, a Humanitarian Use Device (HUD) that has been granted a Humanitarian Device Exemption (HDE) by the FDA may be administered only if such use has been approved by the institution's IRB of record. Once IRB approval is granted, use of the HUD within the approved indication(s), as well as other clinical uses that are intended solely to address the specific needs of an individual patient is allowed. All uses of the HUD for clinical treatment and diagnosis at an institution are to be reported to the IRB at the time of continuing review.
It should be noted that the IRB’s approval for the use of a HUD at a facility to treat or diagnose patients in the course of providing clinical care does not mean that there is IRB approval of a clinical investigation involving the HUD.
The IRB is required to perform its initial review at a convened meeting using the criteria for approval at 21 CFR 56.111. Subsequent continuing reviews - at least annually - may be performed using expedited procedures. Expedited review is permitted because a HUD is an approved device. This determination on continuing review as either full board or expedited is made only by the full board.
Physician Responsibilities for the Use of a HUD
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A physician may utilize a HUD when agreeing to the following:
- Use of the HUD will be done according to the approved indication(s), as well as other clinical uses that are intended solely to address the specific needs of an individual or group of patients.
- The patient(s) must be informed that the HUD is a device authorized under Federal law for use; however, the effectiveness of the device for a specific indication has not been demonstrated; and
- The patient will be provided with the appropriate HUD Patient Information Form and HUD brochure if available.
IRB Submission Requirements for Use of a HUD
Regardless of the intended use, a HUD requires prospective IRB review and approval by the full board, with the exception of Emergency Use of an HDE. For an Emergency HDE, refer to process outlined earlier for ”Single Patient Emergency Use of an Unapproved Medical Device”:
Send the following documentation to the UVA IRB via IRBHSR@virginia.edu Subject: HUD Request
- Humanitarian Use Device Information Form
- Patient Information Document with treatment specific information.
- New Medical Device Application
- The HUD brochure if available
- Any additional Manufacturer information
- FDA approval letter/HDE#
Continuing Review Requirements for HUD
The physician is responsible for fulfilling continuing review requirements to the IRB at least annually. This report must include the following:
- The clinical indications for the use of the HUD in each patient;
- Clinical outcomes of each participant, if known.
Modifications to the HUD
Modifications to the HUD or the clinical use of the HUD are to be promptly reported to the UVA IRB in accordance with the IRB policy for Modifications at UVA.
Emergency Use of a HUD
Off-label use of a HUD in an emergency situation that cannot wait for IRB review and approval may be handled under Single Patient Emergency Use of an Unapproved Medical Device provision provided that the situation meets the FDA criteria under 21 CFR 56.104 (d) and the HUD is not used outside its approved labeling.