A Humanitarian Use Device (HUD) is defined as 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 (Orphan Diseases). An HUD is marketed under an HDE, and is exempt from the requirement of establishing a reasonable assurance of effectiveness. Although the use of a HUD within its approved labeling does not constitute research, the FDA requires IRB approval be obtained before a HUD can be used in a facility.

Physician Responsibilities

  • Obtain IRB approval and institutional clearances prior to first use of the HUD and maintain IRB approval (continuing review) as long as the HUD continues to be used in the institution
  • Ensure that patients receive the labeling information prepared by the HDE holder or an informed consent form approved by the IRB.
  • Ensure that the device is used only by designated individuals in designated facilities approved for HUD use (i.e., individuals and facilities listed in the IRB approved protocol for HUD use)
  • Ensure that the HUD is used within the scope of its labeling, OR submit to the IRB if the proposed use is not within the scope of the approved labelling
  • Report to the HDE holder/FDA and to the IRB any new risk information. Ine ssence, report 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 (21 CFR 814.126(a))
  • Report any patient complaints to the IRB

Request Approval for Clinical Use of a Humanitarian Use Device (HUD)

Clinical Use refers to use of the HUD in accordance with its label, for treatment or diagnosis as part of clinical care (not for research purposes). 

IRB Submissions for Clinical Use of a Humanitarian Use Device (HUD) in accordance with its labelling require the following to be provided in HSERA:

  • HUD Protocol Summary (click here to download template)
  • Cover letter with additional information that may help in the review and document list identifying each attachment (name, version, date)
  • The HUD manufacturer’s product labeling, clinical brochure, and/or other pertinent manufacturer informational materials
  • The FDA HDE approval letter
  • Humanitarian Use Device Consent Form (click here to download template) or the patient information brochure prepared by the manufacturer
Training Requirements
  • Physicians may take the full CITI Human Subjects Protections course if they are otherwise engaged in human subjects research.
  • Physicians may take the standalone Humanitarian Use Devices (HUDs) module if they are NOT otherwise engaged in human subjects' research. Within the CITI Course Enrollment Questions, check the box next to Humanitarian Use Devices (HUDs).

See the CITI Guidance page for more information. 

Request an Emergency Use of a HUD for Clinical Care in a Single Patient

If a physician in an emergency situation determines that IRB / FDA approval for the use of an HUD cannot be obtained in time to prevent serious harm or death to a patient, a HUD may be used within the scope of its labeling or off-label without prior IRB approval. Emergency use situations are those in which:

  • The patient has a life-threatening condition that needs immediate treatment;
  • No generally acceptable alternative treatment for the condition exists that provides an equal or greater likelihood of saving the subject’s life; AND
  • Because of the immediate need to use the device, there is insufficient time to contact the FDA or the IRB.

Physician responsibilities prior to emergency HUD use: 

  1. Determine if the proposed use meets the regulatory definition for emergency use (see above), AND complete as many of the following patient protection measures as possible:
  2. Obtain an independent assessment by an uninvolved physician (i.e., not the referring physician)
  3. Obtain authorization of the HDE holder to use the HUD in the emergency situation.
  4. Obtain informed consent of the patient or his/her legally authorized representative OR, if informed consent cannot be obtained because of an inability to communicate with or obtain legally effective consent form the patient or legally authorized representative, written certification of an uninvolved physician that the conditions warrant emergency use and informed consent cannot be obtained for the aforementioned reasons.
  5. Obtain applicable institutional clearances for HUD use (e.g., EHRS approval)

Physician responsibilities following emergency HUD use

  1. Within 5 days after the emergency use of the HUD, provide written notification to the IRB of the emergency use. Include: identification of the patient involved, the date of the use, and the reason for the use; Outline a schedule for monitoring the patient, taking into account the specific needs of the patient and the limited information available about the risks and benefits of the device.
  2. Submit a follow-up report on the patient’s condition and information regarding the patient protection measures to the HDE holder, who would then submit this information as a HDE report to the FDA.
  3. Report to the HDE holder/FDA and to the 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 (21 CFR 814.126(a)).

Request an Off-Label Compassionate Use of a HUD for Clinical Care in a Single Patient

If a physician in a non-emergent situation determines that there is no generally acceptable alternative treatment or device for the patient’s condition, the HUD may be used off-label in a compassionate use situation. 

IRB Submissions for Compassionate Off-Label Use of a Humanitarian Use Device (HUD) require the following to be provided in HSERA:

  1. An independent assessment by an uninvolved physician (i.e., not the referring physician)
  2. Documentation from the HDE holder allowing the off-label clinical use
  3. A description of the patient(s)' condition and the circumstances necessitating use of the device; an assessment of why alternative therapies or diagnostics are unsatisfactory; a description of schedules to monitor the patient(s) based on the patient(s)' specific needs; an assessment of information about the risks and probable benefits of the device for the proposed patient(s)
  4. Documentation of FDA approval for compassionate use of the HUD (see HDE holder responsibilities), or notification that this is pending
  5. The HUD manufacturer’s product labeling, clinical brochure, and/or other pertinent manufacturer informational materials
  6. The FDA HDE approval letter
  7. Humanitarian Use Device Consent Form (click here to download template) OR the patient information brochure prepared by the manufacturer
  8. Cover letter with additional information that may help in the review and document list identifying each attachment (name, version, date)
  9. Obtain any institutional clearances for the device prior to compassionate use.

If the HUD is already approved for on-label use at the institution, chair concurrence may be utilized for IRB review. If the HUD is not already approved for on-label use at the institution, full convened board review will be required. 

Physician responsibilities following compassionate HUD use
  1. Submit a follow-up report on the patient’s condition and information regarding the patient protection measures to the HDE holder, who would then submit this information as a HDE report to the FDA.
  2. Report to the HDE holder/FDA and to the 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 (21 CFR 814.126(a))

Request Approval for Investigational Use of a Humanitarian Use Device (HUD)

Investigational use refers to research/clinical investigation involving a HUD, off label or in accordance with its label. 

Investigational use of a HUD in accordance with its label

If the investigational use is in accordance with the approved HDE label to collect safety and effectiveness data, please follow submission requirements online here: https://irb.upenn.edu/initial.

Investigational use of a HUD off-label

If the investigational use is NOT in accordance with the approved HDE label, please follow submission requirements online here: https://irb.upenn.edu/initial. A research informed consent form and a standalone protocol will be required. Depending on the proposed use, the use may require submission of an IDE application to the FDA, or be conducted under abbreviated requirements for NSR devices.