- Overview and Definitions
- Ethical Considerations of Emergency Use Provisions
- Emergency Use Criteria
- Emergency Use Requirements
- Consequences of Noncompliance with Federal Regulations
- Tips for submitting Expanded Access - Individual Patient (SPIND)
- Emergency Use Forms
Overview and Definitions
The University and the FDA wish to support a physician’s obligation to treat a seriously ill patient with all available modalities. The emergency use provision in federal regulations allows physicians restricted access to investigational treatments that would be otherwise off-limits [21 CFR 56.104(c) and 21 CFR 56.102(d)].
Contrary to common usage, the terms “emergency use” and “compassionate use” are not synonymous. Become aware of the specific, separate standards for emergency use and compassionate use/expanded use to avoid violating federal regulations and UCSF policy regarding the use of unapproved drugs, biologics and devices.
Different FDA regulations apply to the different types of test article use, and the terminology can be confusing. Use the following definitions:
Ethical Considerations of Emergency Use Provisions
Although treating a seriously ill patient under emergency use provisions is motivated by humaneness and compassion, there are several ethical issues to consider regarding the emergent use of an experimental treatment.
Emergency Use Criteria
The following criteria must be met to comply with federal regulations and University policy on emergency use of unapproved drugs, biologics and devices.
- The test article is used one time per institution to treat a single patient.
- The patient has a condition that is life-threatening or severely debilitating.
- No standard treatment is available.
- There is not sufficient time to obtain IRB review and approval.
- The emergency use is reported to the IRB within five working days; when possible, the treating physician should consult with the IRB prior to use.
- Consent will be sought and documented from the prospective participant or the participant’s legally authorized representative, unless the criteria for the exception to the requirement for consent.
- The treatment is not part of a systematic investigation designed to develop or contribute to generalizable knowledge (that is, treatment will not be incorporated into a project that meets the DHHS definition of research requiring IRB review).
Important Note: The FDA holds the institution to high standards when justifying emergency use. Past lessons tell us that it is very difficult to argue that there’s no acceptable alternative treatment and that there is “not sufficient time” to obtain prior IRB approval.
Emergency Use Request Requirements for Drug or Biologic
If the use of an unapproved drug, or biologic can be justified as emergency use, the physician must fulfill several time-sensitive requirements.
Consequences of Noncompliance with Federal Regulations
If the strict emergency use requirements are not met, both the physician and the institution may suffer strong sanctions.
- Physician noncompliance may result in termination or suspension from treating patients in any and all FDA-regulated studies.
- If the institution fails to provide guidance to physicians and to establish clear procedures, the institution's ability to conduct FDA-regulated research may be restricted.
IRB Oversight
- To help physicians comply with emergency use regulations, the IRB determines whether each use complies. Most often, this is done when the physician discusses the proposed use with an IRB Chair or Vice Chair before the patient is treated. When prior consultation is not possible, a Chair will review the post-use written report. If the post-use written report indicates consent was waived, the IRB Chair or Vice Chair also will review the waiver to determine if it complies with FDA requirements.
- For both the emergency use itself and for a waiver of consent (if applicable), the IRB will issue a letter certifying compliance or informing the physician of noncompliance. In the case of noncompliance, the IRB will follow its usual procedure to determine whether the noncompliance is a serious or continuing problem requiring additional action.
Expanded Access - Individual Patient (SPIND)
In 2017, the FDA began allowing “Alternative IRB Review Procedures” for Individual Patient Expanded Access (sometimes referred to as Single Patient IND). Prior to this FDA decision, Individual Patient Expanded Access requests were required to be reviewed by a convened IRB committee. Note: “Alternative IRB Review Procedures” can only be requested for Individual Patient Expanded Access, not for Expanded Access involving groups.
The UCSF IRB has determined that IRB Chair review is appropriate provided FDA does not decline the physicians request for “Alternative IRB Review Procedures.” If the physician would like to request “Alternative IRB Review Procedures” from FDA, here are the instructions:
- Read the FDA guidance
- When submitting to FDA, use FDA Form 3926 -- Individual Patient Expanded Access Investigational New Drug Application (IND); In June 2021, FDA released a new tool: Expanded Access eRequest, which is a web-based tool that enables physicians to complete, sign, and submit non-emergency Expanded Access (EA) requests to FDA.
- FDA Form 3926 will have a box (Question 10b.) request “Alternative IRB Review Procedures.”
- Once you’ve received the FDA May Proceed Letter, here are the instructions for submitting to the IRB:
- Individual Patient Expanded Access requests are reviewed in iRIS using the same IRB application as a research study.
- Complete the IRB application as completely as possible. Some sections may not apply given your type of submission.
- FDA May Proceed Letter, FDA Form 3926 that you submitted to FDA, Informed Consent Form (IRB template), HIPAA Form, Investigator’s Brochure, any other relevant documents that will assist the IRB Chairperson in the review.
- In the title of the IRB submission, include “Individual Patient Expanded Access” so the submission can be quickly identified by IRB staff.