Emergency Use of a Test Article

Emergency Use

Emergency use: The use of a test article on a human subject in a life-threatening situation in which no standard acceptable treatment is available and where there is not sufficient time to obtain IRB approval. [21 CFR 56.102(d)]

Test article: Any [investigational] drug, biological product, or medical device for human use. [21 CFR 56.102(1)]

IRB approval is required prior to conducting human subject research.  An exception to this is in the one-time use of an investigational drug or device (test article) for a single participant in a life-threatening (emergency use) situation. 

An emergency use of a test article is exempt from prior IRB review and approval, provided that the emergency use of a test article is reported to the IRB within 5 working days of date of the emergency use.  [21 CFR 56.104(c)]

The IRB may be notified prior to an emergency use; however, this notification should not be construed as an IRB approval. Notification is used by the IRB to initiate tracking to ensure that the investigator files a report within the five day time-frame required.
The IRB may choose to request additional information.

Any subsequent use of the test article at Stanford is subject to IRB review and approval.  Only one use of the test article is permitted under the emergency use IRB exception and any subsequent use needs to be done under an IRB approved protocol - however, the FDA acknowledges 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 ["Emergency Use of an Investigational Drug or Biologic," FDA Information Sheet, 1998 Update].

top

Criteria for Emergency Use

All the following must be satisfied:

• Existence of a life-threatening/severely debilitating condition where no standard acceptable treatment is available
• No current IRB approved protocol covering the situation and no time to obtain prior FDA and IRB approval
• Availability of an investigational agent or device which in the opinion of the physician might be beneficial, and
• Availability of an investigational agent or device from a sponsor or elsewhere.
• The Emergency Use of a Test Article is not a systematic investigation designed to develop or contribute to generalizable knowlege.

top

Consent Requirement

Informed consent of the patient or the patient’s legally authorized representative is required, unless both the investigator and a physician (not otherwise participating in the investigation) certify in writing that

1. the patient is confronted with a life-threatening situation;
2. that informed consent cannot be obtained from the patient (because patient cannot communicate or is incompetent to give consent);
3. consent cannot be obtained from the legally authorized representative (unavailable or unknown); and
4. no alternative approved treatment/therapy is available that provides an equal or greater likelihood of saving the patient’s life.

top

Drugs and Biologics - Reporting Requirements to the IRB (and FDA)

The protocol director must submit the following materials to the IRB within five (5) working days following the use of the test article:

• Emergency Use of a Test Article – Notification to the IRB [Form APP-11m] which includes:
• information about the patient
• indication of the life-threatening or severely debilitating nature of the situation
• explanation as to why this drug or treatment was necessary
• and if the emergency use occurred without obtaining prior informed consent, Section D on this form must also be completed: Independent Physician Certification - Emergency Use of a Test Article Without Informed Consent
• Written permission from the manufacturer for the use of the test article under their IND.  Generally the investigator will contact the manufacturer and determine if the drug or biologic can be made available for the emergency use under the company’s IND.
  If the company declines permission or cannot be reached, the investigator should contact the FDA for authorization of the shipment of the drug in advance of the IND submission. In such a case the FDA may authorize shipment of the test article in advance of the IND submission.
  The IRB may request that the investigator contact the FDA to obtain an IND.
• Signed Consent Form, with HIPAA

top

Devices - Reporting Requirements to the IRB (and FDA)

The protocol director must submit the following materials to the IRB within five (5) working days following the procedure:

• Emergency Use of a Test Article – Notification to the IRB [Form APP-11m] which includes:
• information about the patient
• indication of the life-threatening or severely debilitating nature of the situation
• explanation as to why this drug or treatment was necessary
• and if the emergency use occurred without obtaining prior informed consent, Section D on this form must also be completed: Independent Physician Certification - Emergency Use of a Test Article Without Informed Consent
• Written permission from the manufacturer for the use of the test article under their IDE.  Generally the investigator will contact the manufacturer and determine if the device can be made available for the emergency use under the company’s IDE.
  The IRB may request that the investigator contact the FDA to obtain an IDE.
  If the company declines permission or cannot be reached or an IDE does not exist, the FDA expects the investigator to:
  
  • Determine whether the criteria for emergency use have been met;
  • Assess the potential for benefits from the unapproved device and to have substantial reason to believe that benefits exist;
  • Assure that the decision of the investigator that an emergency exists is not based solely on the expectation that IDE approval procedures may require more time than is available.
  • Obtain an independent assessment by an uninvolved physician.

  In addition, if the device is used and there is no IDE:

  • The use must be reported to the FDA within 5 working days (to CDRH or CBER). This report should contain a summary of the conditions constituting the emergency, patient outcome information, and the patient protection measures that were followed.
• Signed Consent Form, with HIPAA

top

FDA contact numbers
   - Drugs and biologicals (CDER)
   - Devices: Center for Devices and Radiological Health (CDRH)
            Tel: 1-800-638-2041 ~  www.fda.gov/cdrh
         or
            Center for Biologics Evaluation and Research (CBER)
            Tel: 1-800-835-4709 or 301-827-1800 ~ www.fda.gov/cber/guidelines.htm.