Presentation: Institutional Review Board: Humanitarian Use Devices (HUDs)

(This presentation is also available in video format with captioning and PDF printer-friendly format.)

Presented by Fabienne Santel, MD

Division of Bioresearch Monitoring
Office of Compliance
Center for Devices and Radiological Health
Food and Drug Administration

Learning objectives

• Define Humanitarian Use Device
• Describe FDA’s approval
• Identify the HDE-holder responsibilities
• Identify the physician responsibilities
• Describe the IRB responsibilities

Topics

• Humanitarian Use Device (HUD)
• Humanitarian Device Exemption (HDE)
• FDA review
• HDE-holder responsibilities
• Physician responsibilities
• IRB responsibilities
• FDA concerns

Humanitarian Use Device (HUD)

• HUD definition
  • Title 21 CFR 814.3(n)
  • A device intended to benefit patients in the treatment or diagnosis of a disease or condition affecting fewer than 4,000 individuals in the US per year
• Office of Orphan Products Development designates a device as a Humanitarian Use Device (HUD)
  • Verifies that the device is designed to treat or diagnose a disease or condition following the parameters in the definition
  • Reviews a description of the device
  • Reviews a description of the rare disease or condition

Humanitarian Device Exemption (HDE)

• HDE Definition
  • Title 21 CFR 814.2
  • A premarket approval application submitted to FDA seeking a Humanitarian Device Exemption from the effectiveness requirements of sections 514 and 515 of the Food, Drug, Cosmetic Act.

Humanitarian Device Exemption Application to FDA

• FDA approval of HDE application
  • HUD does not pose unreasonable risk of injury to patients
  • That the probable benefit outweighs risk of injury from its use
• FDA approval of the HDE
  HDE label states
  • The device is a Humanitarian Use Device
  • The device, to treat or diagnose a specific disease or condition, is authorized by federal law
  • The effectiveness of this device for this use has not been demonstrated
• FDA approval of a HDE application allows the HUD to be marketed

HDE-Holder

• The HDE-holder must
  • Have both HUD designation and approved HDE from FDA before device is shipped to institutions with Institutional Review Board (IRB) oversight
• The HDE-holder is responsible for ensuring initial and continuing IRB review
• The HDE-holder may wish to enforce this by not shipping HUDs to institutions until after receiving documentation of IRB approval
• The HDE-holder is responsible for ensuring
  • the HUD is not administered to or implanted in a patient prior to obtaining IRB approval at the health care facility
• The HDE-holder must
  • Maintain IRB correspondence
  • Report clinical experience, including safety information, to FDA in annual reports

Physician Responsibilities

• Obtain IRB approval and continuing approval
• Follow IRB requirements
• Give patients HUD information packet
• Report serious adverse events and deaths using the Medical Device Reporting system at 21 CFR 803.

IRB initial review of HUDs

• Use approval criteria at 21 CFR 56.111
  • Consideration of the patient’s need for the HUD
  • Likelihood that device is appropriate for the patient’s condition or disease state

IRB continuing review of HUDs

• Follow written procedures for continuing review
  • Convened meeting, or
  • Expedited review is acceptable because it is an approved device

IRB review of HUDs

• An IRB may approve the use of the HUD
  • In general
  • For groups of HUD patients that meet certain criteria
  • Under a HUD treatment protocol, or
  • On a case-by-case HUD basis

IRB limitations on HUD use based on

• One or more measures of disease progression
• Prior use and failure of alternate treatment modalities
• Reporting requirements to IRB or IRB Chair
• Appropriate follow-up precautions and evaluations
• Any other criteria it determines appropriate

IRB withdrawal of approval

•  IRBs must be constituted and act in accordance with the agency’s regulations and withdraw approval for:
  • – Failure to follow IRB or FDA requirements
  • – Unexpected serious harm or death
•  Questions to ask at continuing review
  • – Reporting serious adverse events or deaths
  • – Following IRB conditions of approval or limitations

Medical Device Reporting (MDR) and Humanitarian Use Devices

• Applies to all FDA approved devices
• Serious adverse events and deaths must be reported to FDA and the IRB using the Medical Device Reporting system at 21 CFR 803
• HDE-holders and IRBs should ensure that physicians know about this requirement

FDA Concerns

• Off label use of an HUD
  • IRB should ensure that physicians are made aware of any restrictions or limitations of off-label use at the time of initial review.
  • FDA recommends informed consent and reasonable patient protections measures
    • Monitoring and considering the specific needs of the patient and limited information about risks and effectiveness of the HUD
  • Summary report to IRB and HDE-holder following the use
• Research for HDE-approved indication
  • No Investigational Device Exemption (IDE) required
  • IRB review and informed consent recommeded
• Research outside approved indication
  • Requires an (IDE) 21 CFR 812
  • IRB review and informed consent required

References

• Regulation
  • 21 CFR 814 Subpart H
  • 21 CFR 56 Institutional Review Boards
  • 21 CFR 803 Medical Device Reporting
• Guidance
  www.accessdata.fda.gov/scripts/cdrh/ cfdocs/cfHDE/HDEInformation.cfm
  • List of all HUDs
  • Frequently asked questions and answers

Summary

• Humanitarian Use Device and Humanitarian Device Exemption
• FDA’s approval criteria
• HDE-holder responsibilities
• Physician responsibilities
• IRB responsibilities