Section XVI:

FDA - Regulated Products

WPP #: XVI-2

Title 2:

Humanitarian Use Devices

Effective Date:

04-22-14

Revision History:

06-20-00; 06-07-04; 06-21-06; 02-15-08

Policy Statement

The use of Humanitarian Use Devices in clinical investigations and for treatment or diagnosis must have prospective IRB review according to FDA regulations at 21 CFR 56.103 and 21 CFR 814.124.

Background

A Humanitarian Use Device (HUD) is a “medical device intended to benefit patients in the treatment or diagnosis of a disease that affects or is manifested in fewer than 4,000 individuals in the United States per year” (21 CFR 814.3(n).

A Humanitarian Device Exemption (HDE) is an application to the FDA requesting approval to market a HUD. The FDA approval process for a HDE does not have the same requirements as a drug or device. FDA approval of an HDE allows the applicant to market a HUD, subject to some profit and use restrictions. The HDE is usually held by the manufacturer of the HUD.

There are generally three types of uses for HUDs:

  1. Treatment or diagnosis under a HDE for the HUD’s approved labeling and indication(s). This type of use is not considered a research activity; however federal regulations require IRB approval (21 CFR 814.124)
  2. Treatment or diagnosis under a HDE for an off-label use of the HUD. This type of use is not considered a research activity. IRB approval is not required; however, the HUD/HDE must already have IRB approval for its approved indication. The VCU IRB requires pre-notification, as described below in A.6.
  3. Clinical investigation (i.e., collection of safety and effectiveness data) involving a HUD, whether for its HDE-approved indication(s) or for a different indication. This type of activity is considered research. As such, prospective IRB approval is required.

Data from HUD treatment activities MUST NOT BE USED for research purposes, however, safety information may be provided to the manufacturer.

Procedures and Guidance

  1. IRB Review of HUD for Treatment or Diagnosis:
    1. Initial Review

      The statute and the implementing regulation [see 21 CFR 814.124(a)] require IRB review and approval before a HUD is used. (There is an exception to this rule for emergency situations in which the physician determines that approval cannot be obtained in time to prevent serious harm or death to the patient (see WPP XVI-3 for guidance)). In non-emergency use situations, full board review by the convened IRB is required for initial review of HUDs. The IRB requires the following information, if available, to be submitted for approval either as part of the IRB application or as an attachment:

      • An IRB application with required attachments. The application should include all physicians who will be trained and authorized to use the HUD.
      • Proof of the HDE (FDA letter).
      • A description of the device.
      • Product labeling information.
      • Patient information packet.
      • A clinical protocol describing the use (matching the approved use as outlined in the FDA letter) or a description of how the physician proposes to use the device.
      • A description of how the subject(s) has been or potentially will be identified.
      • An informed consent process and document, as applicable. See Section A.3 of this policy for additional information about informed consent.
      • Description of patient follow-up visits, tests, or procedures.
    2. Continuing Review

      Continuing review of HUDs may be done using expedited review procedures [see 21 CFR 56.110] unless the IRB determines that full board review should be performed. The FDA notes that the expedited review procedures are appropriate for continuing review since the initial review would have been performed by the full board and use of a HUD within its approved labeling does not constitute research.

      The IRB requires the following information to be submitted for continuing review:

      • An IRB continuing review application.
      • A summary of the use that has occurred during the review period including frequency of use, de-identified information pertaining to the patients who received the device, and discussion of any adverse events.
      • Copies of medical reports submitted to the FDA or HDE holder.
      • Identification of any physicians other than the PI who utilized the device during the review period.
      • A copy of the currently approved informed consent document, if any.
    3. Informed Consent Requirement

      The VCU IRB requires that an informed consent process and document be approved, even though federal regulations do not require informed consent. The informed consent document may be provided by the manufacturer. The informed consent process should ensure the patient clearly understands that the effectiveness of the device has not been fully tested, the risks and benefits of the device, as well as any possible alternative treatment options. Most HDE device patient labeling contains a discussion of the potential risks and benefits of the device as well as any procedures associated with the use of the HUD. Patient labeling also states that the device is a humanitarian use device for which effectiveness for the labeled indication has not been demonstrated. This information may be used in the informed consent process.

      The following information should be conveyed to the patient, either through the patient labeling or the informed consent form:

      • A statement that the effectiveness of the device for the use has not been demonstrated;
      • An explanation that the HUD is designed to diagnose or treat the disease or condition described in the HDE labeling (except in an off-label use) 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 that are not described elsewhere, such as in a hospital consent;
      • A description of the use of the HUD;
      • All known risks or discomforts associated with the use; and
      • An explanation of how the HUD will work in relation to the disease or condition.
    4. HIPAA Requirements

      When using a HUD for treatment or diagnosis, the activity is not considered research. As such, an Authorization for research is not necessary. Use of protected health information about a patient defers to HIPAA policy in the clinical practice setting.

    5. Multiple Use of the HUD within the Approved Indication(s):

      Once the IRB has granted approval for the use of the HUD, subsequent use according to the HDE-approved indication(s) should be reported to the IRB at the time of continuing review. The IRB is not required to review and approve each individual use of a HUD; however the IRB can use its discretion in determining how to approve and has the ability to place limitations on the approval.

    6. Use of a HUD outside of the Approved Indication(s)

      Once a HUD is approved by the IRB for its indicated use, the HUD may be used outside of its approved indication(s) for treatment or diagnosis. When this situation exists, the IRB requires the following:

      • Pre-notification via written letter to the IRB including the IRB # of the associated approved HUD protocol (unless the use is an emergency situation) describing the need for the use, as well as when and how the use will occur; IRB approval is not required.
      • The physician obtained patient consent as described in section 3 above. This informed consent does not need to be IRB approved. The informed consent should indicate that the HUD is being used outside of its approved indication.
    7. Medical Device Reporting (MDR)

      The principal investigator is required to submit medical device reports to the FDA, the manufacturer, and the IRB whenever the HUD may have caused or contributed to a serious injury (21 CFR 803.30 and 814.126(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 (21 CFR 803.3). MDR reports must be submitted when the HUD is being used for its approved indications and unapproved indications, as described in section 6 above. MDR reports submitted to the FDA should be submitted to the IRB using the Prompt Reporting mechanism.

  2. IRB Review of HUD for Clinical Investigation:
    1. Initial Review

      When a HUD is being used in a clinical investigation (e.g., collection of safety and effectiveness data), whether for its HDE-approved indication(s) or for a different indication, the investigation is considered research involving human participants. As such, IRB review and approval by the convened IRB is required prior to initiating the research. Investigators should submit a standard IRB application and follow all instructions for attachments. Full board review will occur by the convened IRB.

    2. Need for an Investigational Device Exemption

      Approved Indication: When a HUD is used in accordance with its approved indication(s), FDA considers the study exempt from the requirement for an IDE, even when safety and effectiveness data are collected. As such, an IDE is not required. The IRB does not make a significant risk/non-significant risk determination when the HUD is being used for approved indication(s) and no IDE is needed.

      Unapproved Indication: Clinical investigations using the HUD for an unapproved use or indication must comply with the IDE regulations at 21 CFR Part 812. An IDE is required in this case. The IRB review should include a significant risk/non-significant risk determination unless the determination has already been made by the sponsor. Additional information regarding significant risk/non-significant risk, including definitions, can be found in the following policy: WPP XVI-1: Review of Devices (SR vs. NSR Determination and Actions)

    3. Continuing Review

      The IRB will determine the frequency of continuing review, with a maximum review period of one year. Continuing Review will be conducted by the convened IRB unless it is determined to qualify for expedited review. Investigators should submit a continuing review form and follow all instructions for requested supporting documentation.

    4. Informed Consent Requirement

      An informed consent process and a standard research consent form compliant with 21 CFR 50 should be provided to the IRB for review and approval.

    5. HIPAA Requirements

      When using a HUD in a clinical investigation, the use is considered research and is subject to HIPAA for research regulations. Patient authorization must be obtained for the use of PHI unless the IRB approves a waiver of authorization.

Responsibility

It is the responsibility of the VCU faculty or staff member to apply for prospective IRB review of the use of Humanitarian Use Devices. The VCU IRB will review these applications for approval in accordance with these Written Policies and Procedures.

References

WPP XVI-1: Review of Devices (SR vs. NSR Determination and Actions)
WPP XVI-7: Control of Investigational Drugs, Devices, and Biologics
FDA Medical Device FAQ/Information Sheet: Guidance for HDE Holders, IRBs, Clinical Investigators, and FDA Staff (July 8, 2010)
Humanitarian Use Devices Exemption list
FDA Regulations:
21 CFR Part §814.124,
21 CFR 50
21 CFR 56
21 CFR 812