The FDA’s Office of Good Clinical Practices (OGCP) is an important resource for clinical trial professionals who cannot find the answers they need in the agency’s multitude of regulations, guidances and policies.

OGCP answers questions submitted via email to gcp.questions@fda.hhs.gov, interpreting the FDA’s position, offering advice on how to proceed and pointing out key documents and resources that provide more in-depth guidance. The following questions address IRB requirements for individual patient-expanded access.

Waiver of IRB Requirements for Individual Patient Expanded Access IND

Q: I have reviewed the recently updated FDA guidance documents, “Waiver of IRB Requirements for Drug and Biological Product Studies” and “Expanded Access to Investigational Drugs for Treatment Use — Questions and Answers” as well as updated FDA Form 3926 and am seeking clarification related to FDA’s expectation for IRB review, or what is termed “concurrence”, in the guidance.

Specifically:

• FDA guidance “Expanded Access to Investigational Drugs for Treatment Use — Questions and Answers” Q6 states, “Is institutional review board (IRB) review and approval required for all expanded access categories?”

A6: Except for emergency expanded access use (see Q8) when there is not sufficient time to secure prospective IRB review, an investigator treating a patient with an investigational drug under expanded access is responsible for obtaining IRB review 11 and approval consistent with 21 CFR part 56 before treatment with the investigational drug may begin, regardless of whether the protocol is submitted in a new IND or to an existing IND (21 CFR 312.305(c)(4)). In the case of emergency expanded access use, FDA authorization is still required (§312.310(d)), but it is not necessary to wait for IRB approval to begin treatment.

…

• FDA guidance “Waiver of IRB Requirements for Drug and Biological Product Studies” Section VIII states, “A physician submitting an individual patient-expanded access IND using Form FDA 39268 may select the appropriate box on that form to request a waiver under §56.105 of the requirements in §56.108(c), which relate to IRB review and approval at a convened IRB meeting at which a majority of the members are present. FDA concludes that such a waiver is appropriate for individual patient expanded access INDs when the physician obtains concurrence by the IRB chairperson or another designated IRB member before treatment use begins (no separate IRB approval process or notification to the IRB would be needed).” It is noted that this implies that “concurrence” is NOT IRB approval.
• Form FDA 3926 states, “10.b. Request for Authorization to Use Alternative IRB Review Procedures I request authorization to obtain concurrence by the Institutional Review Board (IRB) chairperson or by a designated IRB member, before the treatment use begins, in order to comply with FDA’s requirements for IRB review and approval. This concurrence would be in lieu of review and approval at a convened IRB meeting at which a majority of the members are present. It is noted that this does not state “…in lieu of review and approval” but is specific to convened IRB review.

Related to these documents, I had the following questions:

1. It is unclear if it is FDA’s expectation that the “concurrence” by IRB Chair (or designated reviewer) is done via an expedited review mechanism (which would technically constitute IRB approval) or if it can be done by an administrative process that documents the concurrence when a waiver is requested (and therefore the “designated IRB member” doesn’t necessarily have to be a designee of the IRB Chair for purposes of expedited review as concurrence is not technically IRB approval). It is noted that the term “concurrence” is used rather than “approval” but there is reference to “designated IRB member” which is often used in the context of expedited review.
2. In addition, my interpretation is that informed consent is still required under 21 CFR 50 for expanded access, including individual patient, so would the review of these requirements be addressed via the concurrence?

A: The IRB chairperson (or designated IRB member) would consider the same information that the full IRB would consider to determine whether to approve the treatment when reviewing and concurring for individual patient-expanded access use.

Informed consent is required for expanded access uses. Review of the informed consent would be part of the IRB review and concurrence process for individual patient-expanded access use.

Q: Just to further clarify the actual review pathway that is allowed, when the IRB chairperson (or designated IRB member) reviews an individual patient-expanded access use request, would the IRB chairperson document their review and concurrence as being done via expedited review (under 21 CFR 56 .110) or done via an “administrative” (non-IRB review) concurrence action?

Specifically, for those institutions that use electronic IRB systems to track and manage IRB reviews, we are trying to figure out if we must route these individual patient-expanded access use requests (when a waiver is requested) via an expedited review pathway or if they can have a separate administrative review pathway.

A: I think you are asking which regulatory IRB review pathway this type of review fits into, full board or expedited or if it would be in a different review pathway. Generally, review of individual patient-expanded access use by an IRB chairperson (or designated IRB member) would follow a different review pathway, that is, one in which the IRB chair or designee reviews the relevant documents (as determined by the IRB) and then his or her decision to concur or not (and/or any questions and responses) is documented.