Definitions:

Humanitarian Use Device (HUD):  A device that is intended to benefit patients by treating or diagnosing a disease or condition that affects or is manifested in less than 4,000 individuals in the United States per year. 

Humanitarian Device Exemption (HDE):  A Food and Drug Administration (FDA) approval for a physician to use a HUD in the clinical treatment of patients.  All of the following FDA requirements must be met for FDA to approve an HDE:

1. The device is to be used to treat or diagnose a disease or condition that affects or is manifested in less than 4,000 individuals in the United States per year;
2. The device would not otherwise be available unless an HDE application were approved;
3. No comparable device, other than another HUD approved under the HDE regulation, or a device being studied under an approved IDE, is available to treat or diagnose the disease or condition; and
4. The device will not expose patients to an unreasonable or significant risk of illness/injury, and the probable benefit to health from using the device outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment.

Procedure:
The UT Southwestern Medical Center (UTSWMC) IRB will review and approve the use of all Humanitarian Use Devices.  The IRB does not generally require review/approval of each individual use of a HUD device as long as the uses of the device fall into the FDA approved indication and IRB protocol approval, as applicable.

Initial IRB Review/Approval.  HUD use must be reviewed and approved by the full board prior to the initial use of the device at a facility operating under the jurisdiction of the UTSWMC IRB.  The physician requesting initial use of a HUD device must submit 25 collated copies of the following:

1. HUD Application Form
2. The HUD product labeling, clinical brochure, and/or other
   pertinent informational materials;
3. The FDA HDE approval letter; and
4. HUD clinical consent form 

Note: Because the use of a HUD is for diagnosis or treatment purposes only, the HIPAA regulations for research are not applicable. Therefore, a HIPAA Research Authorization and/or Waiver of Authorization are not required.

Continuing IRB Review/Approval.  Continuing review of HUD use by the IRB is required at least annually.  Full-board continuing review is required, unless the HUD has not been used since the date of the last IRB approval.  In this case, the expedited review procedure may be followed. 

For full-board review, the requesting physician will submit 20 collated copies of the following information 60 days prior to expiration of IRB approval:

1. A cover letter signed by the responsible physician requesting continuation of the IRB approval of the HUD.  The cover letter should identify the HUD, specify the clinical use of the HUD, and if applicable, summarize any known FDA action(s) taken regarding the HUD since the last IRB review;
2. A summary of all correspondence received from the holder of the HDE since the last IRB review;
3. The current FDA-approved product labeling for the HUD;
4. The current IRB approved consent form; and
5. For each patient in whom the HUD has been used since the last review, a summary of the clinical indications for the use of the HUD and the clinical outcome.

Prompt Reporting Requirements.  Whenever the responsible physician receives or otherwise becomes aware of information, from any source, that reasonably suggests the HUD has or may have caused or contributed to the death or serious injury of a patient, the physician must report such findings to the FDA and the IRB (using the ERGO Adverse Event reporting function) as soon as possible, but no later than 10 working days after learning of the adverse event or problem. 

The responsible physician must report to the IRB any FDA action(s) taken regarding the HUD for which s/he has become aware.  This report will be in a memorandum to the IRB within 10 days of receiving knowledge of such FDA action.  Depending on the nature of the FDA action taken, an IRB Chair may elect to initiate an immediate IRB action to suspend IRB approval for use of the device.

Modification Requirements.  IRB approval is required prior to initiation of any modifications of the HUD and/or of the proposed clinical use(s) of the HUD.  The responsible physician requesting a modification must submit one copy of the following to the IRB:

1. A cover letter signed by the responsible physician describing the modification to the HUD and/or the proposed clinical use(s) of the HUD and the rationale for such modification(s);
2. A copy of the HUD manufacturer’s amendment to the HUD product labeling, clinical brochure, and/or the pertinent manufacturer informational materials corresponding to the requested modification(s) (if applicable);
3. A copy of any FDA HDE amendment/supplement approval letters (if applicable); and
4. A copy of the revised clinical consent form with the modifications highlighted. 

Emergency Off-Label Use of a HUD.  HUDs may be used outside of their approved indications (i.e., off-label) for use in an emergency situation to save the life or protect the physical well-being of a patient provided that the following patient safety measures are met:

Before the HUD emergency use occurs.  If possible, the responsible physician will obtain the following prior to the use of the HUD:

1. Prior FDA approval of the HUD for off-label use;
2. A written assessment, in the form of a memorandum, of the patient’s condition, the circumstances necessitating treatment with the device, a discussion of why alternative therapies are unsatisfactory and information to address the patient protection measures;
3. An independent assessment in writing by an uninvolved physician;
4. Authorization from the HDE holder;
5. Concurrence of an IRB Chair; and
6. Informed consent from the patient/legal representative.

After the HUD emergency use occurs.  The responsible physician will submit a follow-up report on the patient’s condition and clinical outcome to the IRB and to the holder of the HDE.

Non-Emergency Off-Label Use of a HUD.  A HUD may be used off-label when a HUD is the only option available for a patient(s) faced with a serious, non-life threatening condition (i.e., compassionate use).

Before the HUD compassionate use occurs.  The responsible physician will obtain the following:

1. Prior FDA approval of the HUD for off-label compassionate use;
2.  A written assessment, in the form of a memorandum, of the patient’s condition, the circumstances necessitating treatment with the device, a discussion of why alternative therapies are unsatisfactory and information to address patient protection measures;
3. An independent assessment in writing by an uninvolved physician;
4. Authorization from the HDE holder;
5. Concurrence of an IRB Chair; and
6. Informed consent from the patient/legal representative.

After the compassionate use occurs.  The responsible physician will devise an appropriate schedule for monitoring the patient, taking into consideration the limited information available regarding the potential risks and benefits of the device and the specific needs of the patient.

Regulatory References:

21.814 Subpart H

http://www.fda.gov/cdrh/ode/guidance/1381.html