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EMERGENCY USE OF TEST ARTICLES


Federal regulations allow for the emergency use of test articles (unapproved investigational drugs, biologics or devices) (EUTA). Prospective IRB review and approval of the EUTA is not required, provided that such emergency use is reported to the IRB within 5 working days. The LSUHSC-NO (LSUNO) HRPP, however, does request prior notification of emergency use, if time permits, using the procedures described below. Any subsequent use of the test article at the institution or affiliated sites is subject to IRB review.


When Can the EUTA Provision be Used?

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

  1. You wish to use a test article on a human, and
     
  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

    Severly 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.
     
  4. There is no standard acceptable treatment available for the patient’s condition, and
     
  5. There is not sufficient time to obtain prospective IRB approval.


Informed Consent Requirements

For emergency use of a drug, biologic or device, the investigator/treating physician is required to obtain the written informed consent of the participant or the participant’s legally authorized representative. The IRB has developed an Emergency Use Consent Template for this purpose.

An exception to the written informed consent requirement is allowed if both the investigator and a physician who is not otherwise participating in the clinical investigation certify in writing to all of the following [21 CFR 50.23(a)]:

  1. The participant 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 participant.
     
  3. Time is not sufficient to obtain consent from the participant’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.

The IRB has developed the Independent Physician Certification letter template for use under these circumstances. The treating physician may also use this template to communicate with the IRB but his/her certification is typically provided during the IRB notification process (see below).

If, in the investigator’s opinion, immediate use of the test article is required to preserve the patient’s life, and if time is not sufficient to obtain an independent physician’s determination that the four conditions above apply, the treating physician 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.


Physician Responsibilities Before the Test Article is Used

     OBTAIN APPROVAL FROM THE SPONSOR, FDA AND/OR INSTITUTION

  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. Investigational Drugs: Division of Drug Information | (855) 543-3784 | (301) 796-3400 | druginfo@fda.hhs.gov
       
    2. Investigational Biologics: Center for Biologics Evaluation and Research | (800) 835-4709 | (240) 402-8020 | industry.biologics@fda.hhs.gov
       
    3. Investigational Medical Devices: Center for Devices and Radiological Health |301-796-7100 | DICE@fda.hhs.gov
       
    4. On Nights and Weekends: FDA Emergency Call 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.

     NOTIFY THE IRB

  1. Notify the IRB Office of the intended EUTA by completing and submitting Part I of the EUTA application in Kuali Research. Instructions are available in the Kuali Quickguide - Emergency Use of a Test Article.
      
  2. If there is insufficient time to complete the application, notify a staff member of the IRB Office by email or phone of the intended EUTA.
     
  3. This notification should not be construed as IRB approval. Notification will be used by the IRB Office to initiate tracking to ensure that the investigator files a report within the five-day timeframe required by 21 CFR 56.104(c).
     
  4. 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 a formal IRB approval.
     
  5. 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

     NOTIFY THE IRB

  1. The investigator must notify the IRB within 5 working days after the use of the test article [21 CFR 50.23(c)] by completing and submitting the EUTA application in Kuali Research.
     
    1. If an EUTA application WAS submitted in Kuali Research prior to the use of the test article, the investigator will “amend” the original submission by completing Part II of the application.
       
    2. If an EUTA application WAS NOT submitted in Kuali Research prior to the use of the test article, the investigator will complete both Parts I & II of the application.
       
  2. Among other information, the notification will:
     
    1. Describe the test article that was used, including any IND or IDE numbers;
       
    2. Describe the conditions necessitating the emergency use;
       
    3. Describe the status of the participant;
       
    4. Provide a redacted copy of the signed consent document or a signed copy of the Independent Physician Certification Letter.

     NOTIFY THE FDA AND SPONSOR/MANUFACTURER

  1. 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.

     FUTURE USE OF THE TEST ARTICLE

  1. 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 the same facility, 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.


Resources

     HRPP RESOURCES

  1. Emergency Use Consent Template
     
  2. Independent Physician Certification Letter Template
     
  3. Kuali Quickguide - Emergency Use of a Test Article

     FDA RESOURCES

  1. Expanded Access for Medical Devices: https://www.fda.gov/medical-devices/investigational-device-exemption-ide/expanded-access-medical-devices#emergency
     
  2. For Physicians: How to Request Single Patient Expanded Access (“Compassionate Use”): https://www.fda.gov/drugs/investigational-new-drug-ind-application/physicians-how-request-single-patient-expanded-access-compassionate-use
     
  3. Investigational New Drug (IND) Application: https://www.fda.gov/drugs/types-applications/investigational-new-drug-ind-application#emergency
     
  4. Expanded Access | Information for Physicians: https://www.fda.gov/news-events/expanded-access/expanded-access-information-physicians#SubmitRequests