Guidance

Emergency Use of a Test Article in Life-Threatening Circumstances

IRBMED
Aug 22, 2022 12:00 pm
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This guidance describes the circumstances regarding Emergency Use of an investigational product (drug, biologic, or device) and the procedures to be followed before or immediately following the emergency use of an investigational product.

Emergency Use is a form of Expanded Access and is part of the FDA Expanded Access program. For non-emergency use and additional information, see also the IRBMED Expanded Access guidance page. 

Emergency use is defined at 21 CFR 56.102(b)(d) as

  • the use of a test article (drug, biologic, or device)
  • on a human subject in a life-threatening situation
    • in which no standard acceptable treatment is available, and
    • in which there is not sufficient time to obtain IRB approval.

The expanded access emergency use provisions in the FDA regulations, 21 CFR 56.104(c), provide

  • an exemption from prior review and approval by the IRB, as long as
  • the emergency use is reported to the IRB within five working days.

  • When is an Emergency Use appropriate?

    Emergency Use of an FDA-regulated investigational product (test article) may occur in circumstances where it is not feasible to secure IRB approval and/or informed consent from the patient or Legally Authorized Representative (LAR).  Emergency Use is permitted only if all of the following criteria are met:

    • The patient faces a life-threatening or severely debilitating condition. Per HRPP Operations Manual Part 8.IV:
      • Life-threatening means diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted, and diseases or conditions with potentially fatal outcomes where the end point of clinical trial analysis is survival. 
      • Severely debilitating means diseases or conditions that cause major irreversible morbidity. Examples of severely debilitating conditions include blindness, loss of arm, leg, hand or foot, loss of hearing, paralysis, or stroke.
    • The patient is likely to benefit from treatment with the unapproved drug, biologic, or device.
    • No generally acceptable alternative for treating the patient is available.
    • There is no time to use existing procedures to secure prospective IRB approval or, for a device, FDA approval for the use.

  • What are the steps for Emergency Use?

    Always BEFORE the emergency use treatment

    1. Contact the Michigan Institute for Clinical and Health Research IND/IDE Investigator Assistance Program (MICHR/MIAP) at UM-Expanded-Access-Request@med.umich.edu.
      This email contacts MICHR/MIAP directly, and also notifies the Research Pharmacy (level-2 login required) (formerly known as IDS) of the impending emergency use necessity. There is no charge for MICHR/MIAP assistance when utilizing an Expanded Access investigational product, including Emergency Use.
    2. Obtain permission from the investigational product sponsor/manufacturer for the emergency use of the investigational product.
      Some manufacturers may request “IRB approval” before providing the product; MICHR/MIAP and IRBMED will help facilitate this request even if there is not time to submit and review an application beforehand.
    3. Notify the IRBMED Chair-on-Call by contacting the UMHS operator to page the IRBMED Chair-on-Call at (734) 936-4000. Be prepared to answer questions not only about the patient and investigational agent, and plan for administration, but also about the notifications/consultations/approvals sought and/or received from the investigational agent’s sponsor, and from FDA.
    4. For investigational drugs and biologics: Obtain an Emergency IND from FDA. MIAP will provide support for this process.

    As time permits, BEFORE the emergency use treatment

    Any of the below procedures not completed before administration of the investigational agent should still be completed within 5 working days afterward.

    1. Document the approval of the IRBMED Chair-on-Call through a follow-up email detailing the content of the discussion. Attach a print-to-pdf copy of the email within the subsequent eResearch application.
    2. Obtain informed consent from the patient or patient’s Legally Authorized Representative, using the IRBMED Specialty Consent Template for FDA Expanded Access (even without IRBMED document finalization), or using consent template provided by investigational product sponsor/manufacturer.

    Within 5 working days AFTER the emergency use treatment

    1. With MICHR/MIAP assistance, submit an application for IRB acknowledgement of the Emergency Use in the eResearch system within 5 working days of the administration of the product (Application Type 01-1: “Expanded Access …”).
    2. If informed consent was not obtained prior to use, secure an uninvolved, independent physician’s certification that:
      1. It was not feasible to secure the patient’s legally effective consent (for example because the patient was unconscious or sedated or legally incompetent
      2. Time was insufficient to secure consent from the patient’s legally authorized representative
      3. The patient was confronted by a life-threatening situation (including one involving risk of serious, irreversible morbidity), necessitating use of the product.
      4. At the time of the procedure, there was no available alternative method of approved or generally recognized therapy that would have provided equal or greater likelihood of saving the patient’s life or avoiding serious, irreversible morbidity.
    3. Write or dictate a note or report including a statement of who administered the drug or placed the device and why it was used.
    4. With MICHR/MIAP assistance, complete additional required reports. Which reporting responsibilities are yours depend heavily on whether you are the “sponsor” (IND/IDE holder).
    5. Evaluate the likelihood of a similar need for the drug/device occurring again.
    6. If there is a high likelihood of a similar need for the drug/device occurring again, consider whether it is feasible to secure the necessary approvals prior to next use, such as opening of a new “high risk” arm on the trial, or establishing a multi-patient expanded access IND.  MICHR/MIAP can assist you in understanding how to proceed if the situation warrants continued usage of the Emergency Use investigational product.

  • When must FDA be notified of an Emergency Use of an investigational product?

    FDA Expanded Access contacts are available at all hours of the day or night.

    Emergency Use of an investigational drug or biologic product requires an ‘Emergency IND’ from the FDA prior to administration of the agent.

    For Emergency Use of a medical device, prior FDA approval is not expected, if the criteria for Emergency Use are satisfied. The FDA expects the physician to

    • make the determination that the patient's circumstances meet the above criteria; 
    • assess the potential for benefit from the use of the unapproved device;
    • have substantial reason to believe that benefits will exist.

    A physician may obtain an opinion from FDA whether the case meets criteria for Emergency Use prior to investigational device administration. MIAP will facilitate the device-specific reporting.

  • Additional Resources
Tags: Regulatory MICHR Investigator Initiated
Units: Institutional Review Boards (IRBMED)
Topic: FDA (Drugs, Devices & Biologics) Investigator & Study Team Responsibilities Regulations & Policies (Federal, State & Local)
Questions?

Contact us at irbmed@umich.edu or 734-763-4768 / (Fax 734-763-1234)

2800 Plymouth Road, Building 520, Room 3214, Ann Arbor, MI 48109-2800

A list of IRBMED staff is available in the Personnel Directory, or view the list of Regulatory Teams.

Edited By: larkspur@umich.edu
Last Updated: August 22, 2022 12:00 PM

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