Emergency Exemption for Investigational Test Articles

IRB review and approval is not required for the emergency use of a test article, provided that such emergency use is reported to the IRB within 5 working days. Any subsequent use of the test article at the institution is subject to IRB review. 21 CFR 56.104(c)

When can it be used? 

The Emergency Use provision can be used when all five of the following conditions apply:

  1. You wish to use a test article on a human, and
    (Test article means any drug for human use, biological product for human use, medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the act or under sections 351 or 354-360F of the Public Health Service Act.)
  2. the patient is in a life-threatening situation, and
    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. The criteria for life-threatening do not require the condition to be immediately life-threatening or to immediately result in death. Rather, the subjects must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.
  3. a severely debilitating condition exists, and
    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.
  4. there is no standard acceptable treatment available for the patient’s condition, and
  5. there is not sufficient time to obtain IRB approval.

responsibilities before the test article is used:

  1. For the emergency use of an unapproved investigational drug or biologic, an IND is required.
    If the intended participant does not meet the criteria of an existing study protocol, or if an approved study protocol does not exist, and a drug or biologic will be used, the investigator must obtain an emergency IND.  The usual procedure is to contact the manufacturer and determine if the drug or biologic can be made available for the emergency use under the company's IND. If there is not time to apply for an IND, the FDA may authorize shipment of the test article in advance of the IND submission. Requests for such authorization may be made by telephone or other rapid communication means to the FDA.
    1. Drug Products: Division of Drug Information | (888) 463-6332 | (301) 796-3400
    2. Biological Blood Products: Office of Blood Research and Review | (HFM-300) | (301) 827-3518
    3. Biological Vaccine Products: Office of Vaccines Research | (HFM-400) | (301) 827-3070
    4. On Nights and Weekends: Office of Crisis Management & Emergency Operations Center | (866) 300-4374 | (301) 796-8240
  2. For the use of an investigational device, the physician should follow as many patient protection measures as possible.  This includes obtaining:
    1. Informed consent from the patient or a legal representative (see Informed Consent requirements below);
    2. Clearance from the institution as specified by institutional policies;
    3. Concurrence of the IRB chairperson;
    4. An independent assessment from an uninvolved physician; and
    5. Authorization from the IDE sponsor, if an approved IDE exists for the device.

Informed Consent Requirements:

For emergency use of a drug, biologic or device, the investigator is required to obtain the written informed consent of the participant or the participant's legally authorized representative.  Investigators may use the IRB’s Emergency Use Consent template.  

Written informed consent does not have to be obtained if both the investigator and a physician who is not otherwise participating in the clinical investigation certify in writing all of the following [21 CFR 50.23(a)]:

If, in the investigator's opinion, immediate use of the test article is required to preserve the subject's life, and if time is not sufficient to obtain an independent physician's determination that the four conditions below apply, the clinical investigator should make the determination and, within 5 working days after the use of the article, have the determination reviewed and evaluated in writing by a physician who is not participating in the clinical investigation.

  1. The subject is confronted by a life-threatening situation necessitating the use of the test article.
  2. Informed consent cannot be obtained because of an inability to communicate with, or obtain legally effective consent from, the subject.
  3. Time is not sufficient to obtain consent from the subject's legal representative.
  4. No alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the subject's life.

Notification to the IRB:

If time permits, notify the IRB Office of the intended Emergency Use.  Investigators may contact the IRB Office via phone or email.  We suggest completing the IRB’s Emergency Use Form.

This notification should not be construed as IRB approval.

Notification will be used by the IRB to initiate tracking to ensure that the investigator files a report within the five-day timeframe required by 21 CFR 56.104(c).

The FDA regulations do not provide for expedited IRB approval in emergency situations. Therefore, "interim," "compassionate," "temporary" or other terms for an expedited approval process are not authorized.

An IRB must either convene and give "full board" approval of the emergency use or, if the conditions of 21 CFR 56.102(d) are met and it is not possible to convene a quorum within the time available, the use may proceed without any IRB approval.

Some manufacturers will agree to allow the use of the test article, but their policy requires an IRB approval letter before the test article will be shipped. If it is not possible to convene a quorum of the IRB within the time available, the IRB office can prepare a written statement that the IRB is aware of the proposed use and considers the use to meet the requirements of 21 CFR 56.104(c). Although, this is not IRB approval, the acknowledgment letter has been acceptable to manufacturers and has allowed the shipment to proceed.

responsibilities after the test article is used:

  1. The investigator must notify the IRB within 5 working days after the use of the test article [21 CFR 50.23(c)]. The notification should
    1. Describe the test article that was used, including any IND or IDE numbers
    2. The conditions necessitating the emergency use,
    3. The status of the participant,
    4. Confirmation that written consent was obtained,
    5. If written consent was not obtained, provide written certification from the investigator and a physician who is not otherwise participating in the clinical investigation that:
      1. The participant is/was confronted by a life-threatening situation necessitating the use of the test article.
      2. Informed consent was not/can not be obtained because of an inability to communicate with, or obtain legally effective consent from, the participant.
      3. Time is/was not sufficient to obtain consent from the participant's legal representative.
      4. No alternative method of approved or generally recognized therapy is/was available that provides an equal or greater likelihood of saving the participant's life.
  2. For Investigational devices, the emergency use should be reported to the FDA by the IDE sponsor via a supplement within 5 working days from the time the sponsor learns of the use. The supplement should contain a summary of the conditions constituting the emergency, the patient protection measures that were followed and patient outcome information.
  3. FDA regulations require that any subsequent use of the investigational product at the institution have prospective IRB review and approval. If the investigator believes the investigational product may need to be used again at NU, a new protocol submission should be submitted to the IRB.  FDA acknowledges, however, that it would be inappropriate to deny emergency treatment to a second individual if the only obstacle is that the IRB has not had sufficient time to convene a meeting to review the issue.

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