Emergency Use of a Test Article

The 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)].

What does life-threatening mean?

“Life-threatening”, for the purposes of the above section [21 CFR 56.102(d)] includes the scope of both life-threatening and severely debilitating as defined below:

FDA Definition of 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.
FDA Definition of 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.

IRB Requirements

The FDA provides an emergency use provision in the regulations [21 CFR 56.104(c)] which allows an exception from prospective review by the IRB. Emergency use of a test article as defined above does not require review by a convened IRB Panel, but the use must be reported to the IRB. The IRB Chair, Co-Chair, or a Vice Chair will determine whether the use complies with the regulatory requirements.

The investigators must notify the IRB before the emergency use of the test article using the ERICA system. If immediate use of the test article is required to save the life of the participant and there is not sufficient time to contact the IRB, the investigator may proceed with the emergency use. In this case, the use of the test article must be reported to the IRB using the ERICA system as soon as possible and absolutely no later than 5 working days from the time the procedure is conducted or drug is administered.

Notifying the IRB of the emergency use (either before or after the procedure or drug administration) should not be construed as IRB approval. A letter will be issued from the IRB Chair, Co-Chair or Vice-Chair stating whether the use complies with the regulatory requirements.

If the IRB will hold a convened meeting prior to the use of the test article, it is not considered exempt from prospective review by the IRB. The IRB staff should be contacted as soon as possible to facilitate review at the convened meeting.

Is the emergency use of a test article considered "research?"
Emergency use of a test article (21 CFR 56.104(c)) is considered by FDA to be human research. It meets the FDA definition of clinical investigation and requires regulation under the Food, Drug and Cosmetic Act. It also involves the administration of a test article to a human, so it involves human subjects. Therefore under FDA regulations, it is human research.

The research must not be subject to DHHS regulation since DHHS has no corresponding exemption from prospective IRB review. The activity must not meet the DHHS definition of “research” and involve “subjects” as defined by DHHS regulations. In other words, the data from an emergency use may not be reported in a way that implies that the activity was a prospectively planned systematic investigation designed to develop or contribute to generalizable knowledge.

An investigator who is responsible for the emergency use of a drug, where drugs are stored and dispensed by the Investigational Pharmacy, must abide by the following policies:

University of Utah Hospitals and Clinics Policy Manual

Medication Management, INvestigational Drug Use, No. 9-8
Department of Pharmacy Policies and Prodedures, No. 12-12, section IV, item C

Investigational Drug Studies (SOP 18.31) for Primary Children's Medical Center

Informed Consent

Even for emergency use, the investigator is required to obtain informed consent of the subject or the subject’s legally authorized representative. However, the FDA provides an exception from the requirements of informed consent [21 CFR 50.23] as outlined below.

Before the use of the test article, both the investigator and a physician who is not otherwise participating in the clinical investigation must certify all of the following:

The human subject is confronted by a life-threatening situation necessitating use of test article.
Consent cannot be obtained because of an inability to communicate with or obtain consent from the subject.
Time is not sufficient to obtain consent from subject's legal representative.
No alternative generally approved method is available.

If immediate use of the test article is required to save the life of the subject and time is not sufficient to obtain independent determination by another physician, a determination by the investigator shall be made. This determination is to be reviewed and evaluated in writing by a physician who is not participating in the investigation within 5 days after use of article. Use the Certification for Emergency Use of a Test Article without Consent and submit with the Report of Emergency Use in the ERICA system.

The documentation described above must be submitted to the IRB within 5 working days after the use of a test article.

Submitting an Emergency Use of a Test Article Application

Log on to the ERICA system.
Complete a conflict of interest disclosure for this emergency use submission.
On the IRB Studies page, click the Create a New Study Application button.
Complete the first page (Contacts and Title) of the new study application, selecting Emergency Use of a Test Article Application in section 1.7.
Complete the entire emergency use of a test article application by clicking Continue after completing each page. This is a smart form and will automatically select the emergency use pages that will need to be completed.
Attach documentation required, as applicable, for emergency use to the Documents and Attachments page.
- Consent Document or Certification for Emergency Use of a Test Article without Consent.
  - The consent document should not be on the IRB watermark template, as it will not receive an approval stamp.
- Any IND or IDE information (i.e. Investigator's Brochure, etc.)
- Sponsor Protocol or Grant Application, if applicable
- Monitoring or debriefing plans not already described in the emergency use application
- Principal Investigator's Scholarly Record (CV/Resume)
Submit the application to the IRB for review.

Submission Considerations

If the IRB Chair determines that there is time to review a proposed use of the test article (i.e. the test article has not been used yet) at the convened IRB, you will be required to complete the entire new study application and the application will not be considered for emergency use.

If the IRB Chair determines that a reported use of the test article (i.e. the test article has already been used) does not meet the definition of emergency use, you will be required to submit a protocol deviation and the IRB will review the use for non-compliance.