IRB Review Medical Devices: Humanitarian Use Devices (HUD) (Summary) [D54.0000]

• Clinical use of a Humanitarian Use Device (HUD) for treatment and diagnosis is not research. 

• The term “use” refers to the use of a HUD for clinical care according to its approved labeling and indication. The FDA has decided that a HUD, which provides for marketing approval, does not constitute “research” or an “investigation”; however, the FDA has determined that clinical use of a HUD requires prospective IRB review and approval.
• Because a HUD is a legally marketed device, no systematic data is collected; however, Medical Device Reporting (MDR) reports may provide risk and benefit information for continuing review.
• For many HDEs, the HDE holder is required to provide training on the device's use prior to the healthcare provider using it. Such requirements would be specified in the HDE Approval Order.
• The healthcare provider responsible for the IRB-approved HUD device should clearly label and store the device to ensure accountability and traceability and prevent use outside of designated sponsor or IRB restrictions/ limitations. 

• As stated in 21 CFR 814.124(a), the humanitarian device exemption (HDE) holder must ensure that the HUD is administered only to patients at health care facilities having a duly constituted IRB as outlined in the FDA IRB regulations (21 CFR Part 56). The health care provider at such facilities is responsible for obtaining IRB approval before use of the HUD.
• Initial IRB approval should be performed at a convened IRB meeting and continuing review of the HUD is required in accordance with IRB regulations 21 CFR Part 56. The FDA allows continuing review to be conducted using the expedited review procedures (see 21 CFR 56.110) unless the IRB determines that convened board review should be performed.
• The IRB must have among its members (or consultants) the appropriate expertise to perform an adequate review of the use of a HUD at the institution. IRBs may defer in writing to another similarly constituted IRB that has agreed to assume responsibility for initial and continuing review of the use of the devices.
• The IRB does not have to review and approve each individual use of the HUD. The IRB may approve the use of the device in general, for groups of patients clinically appropriate for the device’s intended use.
• The IRB may consider the health care provider’s qualifications through training and expertise with the use of the device. The IRB may place limitations on the use of the device based upon: (1) one or more measures of disease progression; (2) prior use of and failure of the alternative treatments; (3) reporting requirements to the IRB or IRB Chair; (4) appropriate follow-up precautions and evaluations, or; (5) any other criteria IRB determines to be appropriate.

The IRB may at its discretion choose to require new HUD users or HUD investigators to complete the CITI HUD Training Module.

• Since the use of a HUD according to its approved labeling is not research, FDA waives the requirements for informed consent. State law or local institutional policy may require informed consent. The IRB may choose to require informed consent when it approves the use of the HUD in a facility.  
• If informed consent is required, the form or process should include information from the HDE holder’s patient information packet found in the HDE Approval Order. In addition, suggested content includes:
  • An explanation that the HUD FDA approves HUDs based on safety and probable benefit; therefore, the effectiveness of the device for that use has not been demonstrated.
  • A description of any ancillary procedures associated with the use of the HUD;
  • A description of the use of the HUD;
  • Known risks or discomforts; an explanation of the postulated mechanism of action of the HUD in relation to the disease or condition; a statement indicating that the effectiveness of this device for this use has not been demonstrated; and a statement that the patient's information may be shared with a sponsor or the FDA. The IRB may decide to include other information.
• Even when the reviewing IRB does not require informed consent, the healthcare provider should provide patients receiving HUD with information from the HDE holder’s patient information packet, which may be obtained by selecting the HDE number on the HDE Approval Order.

• Physicians should be cognizant that the FDA has made a determination of safety and probable benefit for use of the HUD only within its approved indication(s). If a HUD is used outside its approved indication(s) in an emergency or compassionate situation, the FDA recommends that the physician obtain informed consent from the patient and ensure that patient protection measures are followed.
• The UK IRB requires prospective IRB review and informed consent in a format appropriate for emergency, off-label, or single-subject off-label compassionate use.
  • For any off-label use, the healthcare provider includes the following with the IRB submission:
  • HDE holder documentation allowing off-label clinical use (if available) or attestation that use does not violate existing restrictions or limitations;
  • Justification for off-label clinical use;
  • Circumstances necessitating treatment with the HUD;
  • A discussion of why alternative treatments are unsatisfactory; and
  • Assurances and information about patient protection measures.
• Off-label emergency use follows the same procedures that govern emergency use of an unapproved device, and off-label single-subject compassionate use is requested via protocol exception. (See the Humanitarian Use Device SOP [C3.0200].)
• For emergency or compassionate use, the healthcare provider monitors the patient and submits a report of use to the HDE holder or FDA, including any safety-related information.

• The term “investigational use” is used when a HUD is being used in research to collect safety or effectiveness data.
• A HDE holder may collect safety and effectiveness data for the HDE-approved indications without an IDE.  If the HUD is the subject of a clinical investigation (i.e., safety and effectiveness data will be collected), then IRB approval and informed consent are required because this is an FDA-regulated clinical investigation. 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.
• Clinical investigations of a HUD beyond its approved indication(s) (e.g., for a broader or off-label indication) must be conducted in compliance with 21CFR 812, requiring an IDE if significant risk(SR). IRB approval and research informed consent are required. 

FDA Guidance: Humanitarian Use Device (HUD) Designations

• Holder of the humanitarian device exemption is required to notify FDA of the withdrawal of approval for a humanitarian use device by an IRB within five working days after being notified of the IRB action.
• HDE holders may charge for HUDs used clinically to treat or diagnose a patient. If specific eligibility criteria are met, the manufacturer may sell the device for profit within limits. If a HUD is studied in a clinical investigation of a new indication, the HDE holder may not charge subjects or investigators a price larger than necessary to recover the costs to manufacture, research, develop, and handle the HUD.

All FDA-approved devices are subject to Medical Device Reporting (MDR) requirements as described in FDA regulations (21 CFR 803). 

Clinicians and user facilities are required to submit medical device reports to the HDE holder, FDA, and IRB whenever a HUD may have caused or contributed to a death or serious injury, or has malfunctioned and would be likely to cause or contribute to a death or serious injury if the malfunction were to recur. 

A serious injury means an injury or illness that:

1. Is life-threatening;
2. Results in permanent impairment of a body function or permanent damage to a body structure; or
3. Necessitates medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure.

The HDE holder or manufacturer submits reports to the FDA and all reviewing IRB(s) within 10 working days based on the same criteria.

MDR provides a mechanism for the FDA and manufacturers to identify and monitor significant adverse events involving medical devices. The MAUDE database houses MDRs submitted to the FDA by mandatory reporters (manufacturers, importers, and device user facilities) and voluntary reporters such as health care professionals, patients, and consumers.

• For investigational use of a HUD under an Investigational Device Exemption (IDE), reports of unanticipated adverse device effects (UADE) must be reported to the HDE holder, FDA, and IRB per the Unanticipated Problem and Safety Reporting Policy.

• The use of a HUD according to its approved labeling and indication is generally for treatment or diagnosis, even though such use requires IRB approval. If a HUD is being used according to its approved labeling and indication for treatment purposes, and not in a clinical investigation, then protected health information about a patient may be used or disclosed for treatment or diagnostic purposes without the patient’s authorization under HIPAA.
• If a HUD is being used in a clinical investigation for research purposes, whether or not the use of the HUD is the subject of the investigation, then protected health information about a patient that is used or disclosed for purposes of the clinical investigation requires the patient’s authorization under the HIPAA Privacy Rule. The IRB may waive this authorization if certain waiver criteria are met.