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(Refer to the “Quick Reference Guide for Emergency and Compassionate Use” for quick instructions on what to submit)

Overview

Emergency use:

Emergency use is defined as the use of a test article (drug, biologic, or device) 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 (21 CFR 56.102(d)).

Emergency Use Criteria

  • Patient is in a life-threatening or severely debilitating situation
  • No standard treatment is available
  • There is no time to obtain IRB approval

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.

Compassionate use:

For devices specifically, the FDA recognizes that there are circumstances in which an investigational device is the only option available for a patient faced with a serious, albeit not life-threatening, disease or condition. In these circumstances, (hereafter referred to “compassionate use”) the compassionate use provision allows access for patients who do not meet the requirements for inclusion in the clinical investigation but for whom the treating physician believes the device may provide a benefit in treating and/or diagnosing their disease or condition. This provision is typically approved for individual patients but may be approved to treat a small group.

Definitions

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. [21 CFR 56.102(l)]

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.

What to do/submit for an Emergency or Compassionate Use Situation:

  • Contact the manufacturer to obtain their approval of the plan.
  • For a compassionate use, once the manufacturer’s support is secured, please speak to the FDA, since the FDA must approve all compassionate uses before they occur.
  • A physician not involved in the patient’s care must evaluate the patient’s clinical status and the proposed emergency or compassionate use and provide a letter stating that no other standard acceptable treatment is available for this patient.

You may prepare and submit documentation to the IRB office prior to receiving final approval or support from the individuals or entities named above; however, the IRB cannot provide a letter of acknowledgement for this emergency or compassionate use until all of the following documents have been reviewed:

  1. Written notification of the emergency or compassionate use of a test article in a life-threatening situation. This notification should include:
    1. A description of the patient’s medical history and current situation, including prior treatments for the condition requiring the test article
    2. When the patient will receive the intervention
    3. How the patient will be treated and followed (include details such as dose calculation, dose escalation, and tests/procedures that will be followed)
    4. How this use meets the FDA definition of emergency or compassionate use
    5. Confirmation that this information has been documented in the patient’s medical record
  2. Letter of support from a physician not involved in the patient’s care stating that no other standard acceptable treatment is available for this patient

*Confirm also, that this information has been documented in the patient’s medical record

  1. Form 1
  2. Form 2 for the drug or Form 3 for the device that will be used
  3. An informed consent form (ICF) tailored for this single use OR certification by the treating physician and a physician unaffiliated with this emergency or compassionate use that the criteria for the exception from informed consent were met as per 21 CFR 50.24
  4. Brief specific protocol that explains how the drug or device will be used with the one patient. Per the FDA’s Emergency IND Application Timeline, the protocol is to include:
    1. Rationale for intended use of the investigational drug/device including a list of available therapeutic options tried before resorting to the emergency IND/IDE treatment;
    2. Description of the patient’s disease or condition, including recent medical history and previous treatments;
    3. Proposed method of administration of the drug, dose, or implementation of the device and duration of intervention;
    4. Description of clinical procedures, laboratory tests, or monitoring necessary to evaluate the effects of the drug/device and to minimize its risks

The drug or device manufacturer may also be able to provide you with a protocol used in a similar approved study to submit to the IRB.

  1. The Investigator’s Brochure for the drug or Operator’s Manual for the device.
  2. A statement from the drug or device manufacturer that documents the manufacturer’s awareness of the proposed emergency or compassionate use and supports the use of the drug or device in this patient.

A signed letter is preferred; however, a fax copy or scanned signed letter is acceptable.

  1. A statement from the FDA that it has approved the proposed emergency or compassionate use of the drug or device in this patient.

A signed letter is preferred; however, a fax copy or scanned signed letter is acceptable.

  1. For compassionate use of an unapproved device without an IDE only: a letter of support from Tufts Medical Center leadership that the proposed compassionate use of the device is supported by the institution.

A signed letter is preferred; however, a fax copy or scanned signed letter is acceptable.

No patient identifiers (name, medical record number, etc.) should be included in the above.

Data obtained from uses covered by this procedure cannot be used in a research study.

If the treating physician’s opinion is that immediate use of the test article is required to preserve the patient’s life, and if there is insufficient time to obtain an independent physician’s determination that the criteria for emergency use apply (life-threatening, no standard treatment available, and no time to obtain IRB approval), the treating physician should make the determination and use the article. Within 5 working days after the use of the article, the treating physician should have the determination reviewed and evaluated in writing by a physician who is not involved in the patient’s care. The treating physician must then notify the IRB within 5 working days after the use of the test article by submitting the documents listed above. [21 CFR 50.23(c)].

The need for an investigational drug or biologic may arise in an emergency situation where there is not enough time for submission of an IND number. In such a case, the FDA may authorize shipment of the test article in advance of the IND submission. Requests to the FDA for such authorization may be made by telephone or other rapid communication means [21 CFR 312.36].

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 criteria for emergency use [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. The treating physician and physician uninvolved in the patient’s care must also document this use and that it meets the criteria for emergency use [21 CFR 56.102(d)] in the patient’s medical record.

Some sponsors will agree to allow the use of the test article, but their regulatory policy requires “an IRB letter of concurrence” or “IRB acknowledgement” before the test article will be shipped. If it is not possible to convene a quorum of the IRB within the time available, an IRB Chair or Vice-Chair will review the proposed emergency use and provide a written statement of acknowledgment / concurrence.

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 to determine if the test article can be made available for emergent use under the manufacturer’s IND.

After the Emergency Use

After the emergency use, the treating physician is responsible for ensuring that certain follow-up procedures occur per FDA regulations (see page 2 of the FDA’s Emergency IND Application Timeline).  If it is anticipated that additional patients may require the same test article, a new study submission for this test article must be submitted to the IRB for review and approval by the convened IRB.

Useful Links

Expanded Access

FDA contacts for obtaining an emergency IND

Product Office/Division to Contact
Drug products Division of Drug Information
(888) 463-6332
(301) 796-3400
Biological blood products Office of Blood Research and Review
(240) 402-8360
Biological vaccine products Office of Vaccines Research and Review
Contact the Office of Communication, Outreach and Development at:
(240) 402-7800
On nights and weekends Office of Crisis Management & Emergency Operations Center
(866) 300-4374
(301) 796-8240