FDA regulations ordinarily require prior approval from FDA and an IRB for research use of an investigational drug, biologic, or device. Exceptions to this rule apply in very limited cases, including life-threatening emergencies. This guidance describes the circumstances when emergency use is appropriate and the procedures that must be followed before or immediately following an emergency use.
When is an Emergency Use Appropriate?
Emergency use of an FDA-regulated test article may occur only in those circumstances where it is not feasible to secure prospective FDA and IRB approval or informed consent of an individual participant. Emergency use is permitted only if all of the following criteria are met:
- The patient faces a life-threatening condition (e.g., a serious disease or condition such as a sight-threatening or limb-threatening condition, as well as other situations involving risk of irreversible morbidity) that requires immediate treatment.
- The patient is likely to benefit from treatment with the unapproved drug, biological, or device.
- No generally acceptable alternative for treating the patient is available.
- There is no time to use existing procedures to secure prospective FDA and IRB approval and/or informed consent.
Absent an emergency, an investigational drug or device may not be used without prior IRB (and sponsor/FDA) approval of a protocol or any necessary amendments.
What is the Procedure for Reporting an Emergency Use to the IRBMED?
Call and e-mail the IRBMED office as soon as the decision to use an unapproved test article is made, prior to the treatment or procedure if at all possible. After hours and on weekends/holidays, in addition to e-mailing the office, ask the UMHS operator (734) 936-6267 to page the IRBMED chair on call. File a formal report of the emergency use in eResearch within 5 calendar days of the use. Indicate in section 1.12 whether the report is for an investigational drug/biologic or for an investigational device.
When Must FDA Be Notified?
Even in an emergency where it is impossible to secure an IND or IDE in advance, FDA must be consulted prior to use. Contact information (24/7) for drugs/biologics and for devices is available on FDA’s website. Note: if sponsor approval is secured, the researcher is encouraged to request written assurance from the sponsor that FDA approval also has been secured.
What Other Procedures are Required?
If time permits prior to treatment with an investigational agent, the principal investigator (or other individual using the investigational agent and qualified to consent subjects) should secure the following:
- An independent assessment by a physician uninvolved with the investigation, as required in 21 CFR 50.23. The assessment must certify the physician’s agreement that all of the criteria have been met:
- The subject was confronted by a life-threatening situation (including one involving risk of serious, irreversible morbidity), necessitating use of the product.
- At the time of the procedure, there was no available alternative method of approved or generally recognized therapy that would have provided equal or greater likelihood of saving the subject’s life or avoiding serious, irreversible morbidity.
- Informed consent from the recipient or recipient’s legally authorized representative, or an outside physician’s certification that: (1) it was not feasible to secure the recipient’s legally effective consent (for example because the recipient was unconscious or sedated or legally incompetent); and (2) time was insufficient to secure consent from the recipient’s legal representative.
- Concurrence from an IRBMED Chair or Vice Chair that there is an emergency or, preferably, prospective IRBMED approval (in which case the use is not an emergency use).
- Permission from the IND or IDE holder (i.e., the sponsor of a trial/drug or device manufacturer).
Guidance for Principal Investigators/Research Staff Following an Emergency Use
Promptly following an emergency use (and in any event within 5 calendar days), the PI must:
- Obtain an independent physician assessment if time did not permit prior to the treatment or procedure.
- Write or dictate a note or report including a statement of who administered the drug or placed the device and why it was used.
- Submit a report via eResearch.
- Submit a report to the sponsor (IND/IDE holder).
- If you are the sponsor, notify the FDA of the emergency use and provide FDA with a written summary of the conditions constituting the emergency, subject protection measures, and results.
- Evaluate the likelihood of a similar need for the drug/device occurring again.
- Refrain from further emergency use until any necessary approvals have been secured (e.g., opening of a new “high risk” arm on the trial), even if the conditions for an emergency use otherwise exist.
- Other than mandatory reports to FDA or the sponsor, do not use data related to the emergency use in any publication or report on a related research project.
Note: subject to VERY limited exceptions, FDA prohibits additional emergency uses that depart from approved investigational plans and IRB protocols.
Last Updated: 3/6/2012