Emergency Use of IDE/IND (2024)

From the FDA Information Sheets, Guidance for Institutional Review Boards and Clinical Investigators, 1998 Update.

FDA defines theemergency usemeans the use of a test article 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. [21CFR 56.102(d)]

FDA Emergency Use Guidance

When can Emergency Use be used?

Generally, IRB approval is required prior to conducting human subjects research. However, there is an exception to this is the one-time use of an investigational drug, biologic or device for a single subject in a life-threatening situation. This is called Emergency use.

The Food and Drug Administration (FDA) defines ‘emergency use’ as the use of a test article 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 [21CFR 56.102(d)]. Test articles are any drug, biological product, or 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.

Emergency use of an unapproved investigational drug or biologic requires an Investigational New Drug (IND) application to the FDA. This guidance outlines the UI HSO/IRB requirements for requesting an emergency use of an Investigational New Drug Application (IND), Investigational Device Exemption (IDE) and requirements for informed consent.

Criteria for Emergency Use

The emergency use provision [21 CFR 56.104(c)] is an exemption from prior IRB review and approval. The exemption allows for ONE emergency use of a test article without prospective IRB review. It may be used ONLY under the following conditions [as defined in 21 CFR 56.102(d)]:

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 knowledge.

Informed Consent Requirement

The process of informed consent must meet FDA requirements [21 CFR 50.25]. The Principal Investigator (PI) is required to obtain legally effective informed consent from the subject or the subject’s legally authorized representative, using an appropriate consent document that includes all required elements for informed consent. The consent document must also contain the standard and HIPAA Privacy Authorization. The PI may use the UI IRB Informed Consent Document template and HIPAA Authorization or adapt a consent form from a previously approved research study involving the use of the same investigational drug or biologic.

Exception from Informed Consent Requirement

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

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

Steps to request Emergency Use of an investigational drug (IND) or investigational device exemption (IDE)

Initial investigator submission

The investigator must contact the Human Subjects Office (HSO)

During business hours, call (319-335-6564) or email (irb@uiowa.edu) and ask for staff member that deals with emergency use submissions.
If the request is urgent or after normal business hours, email Kay Lewis (Kela-Lewis@uiowa.edu), Tony Quinlan (Tony-Quinlan@uiowa.edu) or Michele Countryman (Michele-Countryman@uiowa.edu) and provide the information below.

Provide the following information:

Evidence that the situation is life-threatening and/or severely debilitating
Justification that no standard acceptable treatment is available
Explanation why there is not sufficient time to obtain IRB approval (IRB-01 meeting every Thursday and every other Monday)
Letter of authorization (LOA) from the manufacturer or sponsor supplying the test article (if applicable)
Copy of documentation submitted to the FDA to and approval letter from the FDA that the Investigator may proceed with the treatment

IRB Chair Review of emergency use submissions

The IRB Chair will review of emergency use submissions. If there is not a convened IRB-01 meeting within the time restrictions, the Chair will determine if the case meets the emergency use criteria. If so, the IRB Chair will provide a letter to the investigator outlining the acknowledgment of the emergency use and explaining there is not time for prospective IRB approval. If the sponsor/manufacturer agrees to allow the use of the test article but requires an IRB approval letter before they ship the test article, the investigator will provide the sponsor with a copy of the letter from the IRB Chair.

IRB review of emergency use submissions

IRB notification does not mean the IRB approved the emergency use. The PI must file a report to the UI IRB (and FDA) within five-days. The IRB will review the investigator’s report at the next IRB-01 Full Board meeting to assess whether the emergency use was justified.

PI submission required after Emergency Use of a Test Article

Notify the IRB (and FDA) within five (5) working days following the use of the test article [21 CFR 50.23(c)] to include:

status of the patient
indication of the life-threatening or severely debilitating nature of the situation
explanation as to why this drug or treatment was necessary
a copy of the signed Informed Consent Document with Protected Health Information (PHI) redacted
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:

The participant is/was confronted by a life-threatening situation necessitating the use of the test article.
Informed consent was not/cannot be obtained because of an inability to communicate with, or obtain legally effective consent from, the participant.
Time is/was not sufficient to obtain consent from the participant’s legal representative.
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.

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.

Subsequent Emergency Use situations

FDA regulations and University of Iowa policy expect that emergency use of a test article without prospective IRB approval is a one-time occurrence. Any subsequent use of the investigational product for additional patients at UI must have prospective IRB review and approval.

However, the FDA and UI IRB-01 acknowledge that it is inappropriate to deny emergency treatment to a second qualified individual if the only obstacle is that the IRB is unable to convene a meeting to review the issue.
The investigator must notify the IRB if there are additional individuals that need the emergency treatment.
If the investigator anticipates similar emergency situations in the future, s/he should submit an IRB application, Consent Document, and protocol to the IRB for full board review and approval as soon as possible.

References:

UI Investigator’s Guide/IRB Standard Operating Procedures at the University of Iowa – section on Emergency Use of an Investigational Drug or Device
FDA regulations on Emergency Use of an IND 21CFR312.54 and 21CFR.312.310
Exemption from IRB requirement 21CFR56.104c
Exemption from general requirements of informed consent 21 CFR 50.23
Emergency Use of an Investigational Drug or Biologic
Emergency Use of Devices
Expanded Access