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Emergency Use of an Unapproved Drug, Biologic or Device

Overview

Emergency use is defined as the use of an investigational drug or biological product with 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)]. The emergency use provision in the FDA regulations [21 CFR 56.104(c)] is an exemption from prior review and approval by the IRB. The exemption, which may not be used unless all of the conditions described in FDA Regulatory Criteria 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. If the test article in question is listed on the List of Previous Emergency Uses of Test Articles at UCI, the investigator will need to submit an IRB Application for review and approval.

The emergency use of an unapproved investigational drug or biologic requires an IND. If the intended subject does not meet the criteria of an existing study protocol, or if an approved study protocol does not exist, the usual procedure is for the investigator to contact the manufacturer and determine if the drug or biologic can be made available for the emergency use under the company's IND.

UCI requests that the investigator notify the IRB prior to the emergency use of a test article by completing the Notification Form: Emergency Use of a Test Article. There are two parts to this form. Part I must be completed prior to the emergency use of a test article. Part II must be completed within 5 business days after the emergency use. The IRB will review the notification form to determine whether the circumstances will follow regulatory requirements for use of a test article.  The IRB will monitor the emergency use of test articles at UCI to ensure that continued use does not occur (as this constitutes research which would require prospective IRB review and approval).

Emergency Use Forms

  1. Notification Form: Emergency Use of a Test Article
  2. Emergency Use Consent Form
  3. Memorandum of Understanding Related to the Use of Data Obtained Under Emergency Use

Procedure for Seeking Emergency Use of a Test Article from a Manufacturer

An investigator who wants approval of an emergency use of a test article should first check the List of Previous Emergency Uses of Test Articles at UCI.

Drugs: If the drug or biological product is not listed, the investigator should contact the manufacturer to determine if the product can be made available (for one, specific patient) under the company’s IND; or if the company declines or cannot be reached, the investigator can contact the FDA for an emergency IND.

Devices: The investigator may contact the manufacturer to determine if the product can be made available. The investigator should ensure that the FDA will be notified immediately after the unapproved device is shipped for an emergency use. An unapproved device may not be shipped in anticipation of an emergency. If the company declines or cannot be reached, the investigator can contact the FDA.

  • For Drug Products - (301) 827-4570
  • For Biological Blood Products - (301) 827-3518]
  • For Biological Vaccine Products - (301) 827-3070
  • For Medical Devices - (301) 594-1190
  • For Nights, Weekends, Holidays – (866) 300-4374 / (301) 443-1240

For additional information, Investigators should review the FDA Information Sheet: Emergency Use of an Investigational Drug or Biologic

Informed Consent for Emergency Use

The investigator should obtain the informed consent of the patient or his/her legally authorized representative (LAR). A witness should also be present during the informed consent process and should sign the consent form along with the investigator. An emergency use consent form template is available for tailoring for the specific emergency use situation. Note: No other emergency use consent form should be signed by the patient or the LAR (e.g., drug manufacturer consent for emergency use).

If the patient is unable to provide consent and a LAR is not available, but a life-threatening situation necessitating the immediate use of the test article is present, an exception for the informed consent requirement may apply. In this situation, both the investigator and a physician who is not otherwise participating in the emergency use situation must certify in writing on the Notification Form: Emergency Use of a Test Article that the following criteria are met:

  • the patient is confronted with a life-threatening situation necessitating the immediate use of the investigational drug, agent, biologic or device;
  • the patient is unable to provide effective consent;
  • there is insufficient time to obtain consent from the patient's legally authorized representative; and
  • no available alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of treating the patient's condition.

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 IRB recommends in the case that a patient is not able to consent, that investigators prospectively obtain the IRB Chair's determination that the situation meets the criteria for the exception from the requirement to obtain informed consent.  If it is not possible, the assessment will be conducted retrospectively.

Disposition of Data Obtained Under Emergency Use Provision

The Office of Research obtained the following guidance from the Food and Drug Administration's Center for Drug Evaluation and Research and the Office for Human Research Protections (OHRP), two federal agencies that regulate the conduct of human subjects research.

The FDA requires data from all investigational uses, including the Emergency Use provision, to be retained and, in the case of commercially sponsored research, submitted to the sponsor when requested.

The FDA considers that when an investigator conducts an emergency use of a test article in a life-threatening situation without prior IRB review, the activity is research and the patient is a subject. As such, FDA may require data from an emergency use of a test article in a life-threatening situation to be reported in a marketing application.

Therefore, reports by the sponsor/manufacturer to the FDA may include Emergency Use data, but such data may not be compiled with research data for publications or other reports, except possibly for single case reports.

Step by Step Instructions for Investigators: Emergency Use of a Test Article

  1. At any stage in the following process, for assistance in determining whether an emergency use of a test article in a life threatening situation meets the criteria for use, contact the UCI Human Research Protection staff at one of the following numbers (during business hours (M-F, 8-5)): IRB Administrators: 949-824-3711 or 949-824-2576.
  2. Check the List of Previous Emergency Uses of Test Articles at UCI.
  3. If the drug or biological product is not listed, contact the manufacturer to determine if the product can be made available (for one, specific patient) under the company’s IND; or if the company declines or cannot be reached, contact the FDA for an emergency IND.
  4. Complete the entire Part I of the Notification Form: Emergency Use of a Test Article.  This includes Sections I-III.
  5. Complete the Emergency Use Consent Form – this will be the consent form used to consent the patient.
  6. Submit via fax ((949) 824-1465) or e-mail the completed Part I of the Notification Form: Emergency Use of a Test Article and Emergency Use Consent Form template to the IRB.  Part I of the Notification Form: Emergency Use of a Test Article must be signed by the investigator (and physician not involved in patient’s treatment – as applicable).    
  7. If unable to obtain prospective informed consent from the patient, the investigator should prospectively confirm with the IRB Chair that the waiver of consent is appropriate.   In addition, as part of completing Part I of the Notification Form: Emergency Use of a Test Article, if the investigator is unable to prospectively obtain informed consent, the investigator should proceed by following the steps outlined in Section II.  A physician not involved in the care of the patient must confirm (via signature) that the criterion for a waiver of informed consent has been met. The current biomedical IRB Chairs are Dr. Tahseen Mozaffar and Dr. Kenneth Linden.
  8. Upon receipt of the Notification Form: Emergency Use of a Test Article and Emergency Use Consent Form, HRP Staff will notify the IRB (i.e., the IRB Chair or a designee not involved in the patient's care). The IRB will review the Notification Form: Emergency Use of a Test Article to determine whether the circumstances will follow regulatory or legal requirements for use of a test article.  Note: Clearance from UCIMC Health Services Administration may also be necessary.
  9. The IRB will monitor the emergency use of test articles at UCI to ensure that continued use does not occur (as this constitutes research which would require prospective IRB review and approval).
  10. Within five working days of the emergency use, the investigator must provide the IRB with follow-up information and documentation regarding the emergency use.  This is a federal requirement. To fulfill this requirement, complete and submit via fax or e-mail Part II of the Notification Form: Emergency Use of a Test Article.  Also, provide written verification of approval from the IND/IDE holder authorizing release of the test article. This may have been authorized verbally, but written confirmation should be provided.
  11. The IRB will review the completed Notification Form: Emergency Use of a Test Article at a convened meeting to determine whether the circumstances follow regulatory requirements for the emergency use of a test article, consent was obtained in accordance with FDA regulations, or the circumstances met the exception to the requirement for consent. The Notification Form: Emergency Use of a Test Article will be signed by the IRB Chair and a copy provided to the investigator.
  12. The investigator should maintain copies of all paperwork involved in the emergency use, including the Notification Form: Emergency Use of a Test Article signed by the IRB Chair.
  13. There will be additional paperwork and report filing as required by sponsors, drug companies, and the FDA (such as follow up/ annual reporting requirements).  This is the responsibility of the UCI investigator.  The investigator should work with their sponsor and FDA contacts to determine their reporting responsibilities.

List of Previous Emergency Uses of Test Articles at UCI:

  • BAT AB
  • Clofazimine
  • Diethylcarbamazine
  • Epicel
  • IV Ribavirin
  • Varizig
  • Vascular Reconstruction Device and Delivery System (Codman Enterprise)
  • Yondelis
  • Gliovac
  • RO5424802 (AF-802) (Alectinib)
  • GBM6 Tumor Lysate
  • Allopregnanolone (SAGE 547)
  • Uridine Triacetate
  • Graftmaster RX Coronary Stent Graft System
  • CPI-0610
  • Indoximod

Regulations:

 

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