Emergency Use of an Unapproved Drug, Biologic or Device

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. The investigator will need to submit an IRB initial review application for review and approval within 25 business days.

The emergency use of an unapproved investigational drug or biologic requires an Investigational New Drug (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.

UC Davis requests that the investigator contact the IRB Administration or an IRB Chair prior to the emergency use of a test article. If there is (was) insufficient time to obtain IRB approval, review and follow the Worksheet: Emergency Use (HRP-322) to meet regulatory criteria for use. Use the Emergency Use Consent Document (HRP-506) to prepare your consent document.

Note: Within Standard Operating Procedure (SOP) 1509 “Emergency or “Compassionate” Use of Unapproved Drugs, Biologics or Devices”, UC Davis Health provides direction on the appropriate use of investigational products under the jurisdiction of the FDA when treating a seriously ill patient when standard treatment is unavailable or not effective.

Emergency Use Forms

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

Drugs: 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) 796-3400
  • For Biological Blood Products – (240) 402-3400
  • For Biological Vaccine Products – (240) 402-7800
  • For Medical Devices – (301) 594-1190
  • For Nights, Weekends, Holidays – (866) 300-4374 / (301) 796-8240

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

Procedure for Procuring an Investigational Drug or Biologic

The investigator must confirm with the manufacture that the drug, biologic or device manufacture is will in and able to provide the test article for emergency use.

Consult with UCDMC Investigational Drugs Pharmacy regarding the procurement and cost associated with the investigational drug or biologic; all investigational drugs or biologics utilized in the emergency/treatment IND must be dispensed through the IDS Pharmacy.  The IDS Pharmacy will report to the IRB any concerns regarding the potential misuse of an investigational drug or biologic.

If the cost for procurement of the investigational drug exceeds $1000 (including any costs associated with shipping or transportation of the product) and the physician prescriber does not having funding to support the cost of procurement of the agent, the Clinical Pharmacology Consult Service (CPCS) must be contacted for review and approval of the request PRIOR to initiation of drug procurement.  If a prescriber proceeds with procurement of the agent without CPCS approval, the prescriber and/or their department will be responsible for all costs related to procurement of the investigational agent.

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 Emergency Use Consent Document (HRP-506).

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 involved in the situation, must certify 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 prospectively confirm with a physician not involved in the research will certify in the medical record and in writing to the IRB within five business days that the criterion for a waiver of informed consent has been met.  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. Review UCDHS Policy 1509 “Emergency or “Compassionate” Use of Approved Drugs, Biologics or Devices and  Worksheet: Emergency Use (HRP-322).
  2. 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 UC Davis IRB Administration staff at one of the following numbers (during business hours (M-F, 8-5)): IRB Director: 916-703-9154. Or contact the IRB Biomedical Chairs: Dr. John Anderson 916-734-7210 or Dr. John MacMillan 916-734-7506.
  3. 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.If using an investigational drug or biologic the investigator must consult the UCDMC Investigational Drugs Service (IDS).
  4. Complete the Emergency Use Consent Document (HRP-506) – this will be the consent form used to consent the patient.
  5. If unable to obtain prospective informed consent from the patient, the investigator should prospectively confirm with a physician not involved in the research will certify in the medical record and in writing to the IRB within five business days that the criterion for a waiver of informed consent has been met.
  6. Within 5 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.

References:

UC Davis Health Emergency or “Compassionate” Use of Unapproved Drugs, Biologics or Devices (Policy 1509)

UC Davis Health Innovative Care Policy (Policy 2516)

Worksheet: Emergency Use (HRP-322)

Emergency Use Consent Document (HRP-506)

FDA Information Sheet: Emergency Use of an Investigational Drug or Biologic