- General Overview
- Exception from Informed Consent Requirement
- FDA contacts for obtaining an emergency IND
In the rare event that a subject does not meet the inclusion criteria of an IRB approved research study and the use, administration of an investigational drug, device, biologic, etc., is indicated emergently for use, a research application may be reviewed by emergency exemption procedure.
Emergency use is defined as the utilization of an investigational drug, device, biologic, etc. (a "test article"), on a human research subject with a life-threatening situation in which no standard acceptable treatment is available, and in which there is not sufficient time to obtain full IRB approval [21 CFR 56.102(d)], and, where applicable, standard treatment options have been exhausted.
The emergency use provision in the U.S. Food and Drug Administration (FDA) regulations [21 CFR 56.104(c)] is an exemption from prior IRB review and approval. The exemption, which may not be used unless all of the conditions described in 21 CFR 56.102(d) exist, allows for one emergency use of a test article without prospective IRB review. FDA regulations require that any subsequent use of the investigational product at the institution have prospective IRB review and approval.
Per the FDA, life threatening, for the purposes of section 56.102(d), includes the scope of both life threatening and severely debilitating, as defined below:
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.
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 FDA regulations do not provide for expedited IRB approval procedures in emergency situations. Therefore, "interim," "compassionate," "temporary" or other terms for an expedited approval process are not authorized. An IRB must either convene and provide "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 sponsors will agree to allow the use of the test article, but their regulatory 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, some IRBs have sent to the sponsor 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 an "IRB approval," the acknowledgment letter has been acceptable to manufacturers and has allowed the shipment to proceed.
If an unapproved investigational drug or biologic must be employed emergently, an investigational new drug number (IND) is required. The typical procedure in this instance is to contact the manufacturer of the test article and determine if the test article can be made available for emergent use under the company's IND.
back to topException from Informed Consent Requirement
Even for an emergency use, the Principal Investigator is required to obtain written informed consent of the research subject or the research subject's legally authorized representative unless both the Principal 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)]:
- The research subject is confronted by a life-threatening situation necessitating the use of the test article.
- Informed consent cannot be obtained because of an inability to communicate with, or obtain legally effective informed consent from, the subject.
- Time is not sufficient to obtain informed consent from the research subject's legal representative.
- No alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the research subject's life.
If, in the Principal Investigator's opinion, immediate use of the test article is required to preserve the research subject's life, and if time is not sufficient to obtain an independent physician's determination that the four conditions above apply, the Principal 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 independent of the research study. The Principal Investigator must notify the IRB within 5 working days after the use of the test article [21 CFR 50.23(c)].
The need for an investigational drug or biologic may arise in an emergency situation that does not allow time for submission of an IND number. In such a case, 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 [21 CFR 312.36].
FDA contacts for obtaining an emergency IND:
Drug product:
Drug Information Branch
(HFD-210)
301-827-4573
Biological blood products:
Office of Blood Research and Review
(HFM-300)
301-827-3518
Biological vaccine products:
Office of Vaccines Research and Review
(HFM-400)
301-827-0648
Biological therapeutic products:
Office of Therapeutics Research and Review
(HFM-500)
301-594-2860
On nights and weekends:
Division of Emergency and Epidemiological Operations
(HFC-160)
301-443-1240
