Prompted by a substantial increase in requests for individual patient access to investigational drugs and biologics to treat COVID-19, the U.S. Food & Drug Administration (“FDA”) issued guidance on June 2, 2020 that outlines key factors and procedures that Institutional Review Boards (“IRBs”) should consider when reviewing such non-emergency requests.

In the guidance, the FDA recommends that IRBs:

• Consider establishing procedures for a single IRB member to review an expanded access submission for an individual patient. Except for emergency expanded access use[1], a physician who wishes to treat a patient with an investigational drug under expanded access is responsible for obtaining IRB review and approval consistent with 21 C.F.R. Part 56 before beginning treatment.[2] However, the FDA permits physicians to obtain concurrence by the IRB chairperson or by a designated IRB member in lieu of a review and approval at a convened IRB meeting at which a majority of the members are present. Physicians may indicate to the FDA their intent to obtain concurrence when submitting the streamlined FDA Form 3926 for individual patient expanded access requests, which includes a checkbox for the physician to opt for the alternative IRB review procedure. In the guidance, the FDA explains that the IRB’s procedures for review by a single member should (i) reflect the information that the IRB deems relevant for a single IRB member review, and (ii) ensure that the IRB member documents the decision to concur or not concur with the treatment.
• Focus the review of an expanded access request for an individual patient on assessing the risks and benefits for the specific patient involved, based on their unique clinical characteristics. In other words, IRBs should determine whether the risks associated with the proposed treatment have been minimized for the particular patient and whether such risks are reasonable in relation to anticipated benefits for that patient. In the guidance, the FDA clarifies that it does not expect that a formal protocol will be necessary for the IRB to make these determinations. Instead, a thorough patient history and treatment plan can suffice, provided they include the following information: (i) the proposed daily dose, route, and frequency of administration, duration of planned treatment, criteria for discontinuation of treatment, and planned dose modifications for adverse events; (ii) the planned monitoring for adverse events, response to treatment, and changes in clinical status, as well as proposed modifications to the treatment plan to mitigate risks to the patient, if appropriate; (iii) key details of the patient’s history, including diagnosis and summary of prior therapy, information regarding a patient’s relevant clinical characteristics (e.g., comorbid conditions; concomitant medications) necessary to assess the potential for increased risks of the drug; and (iv) a summary of known risks of the drug. The FDA notes that additional information may be necessary to facilitate IRB review of expanded access requests for intermediate-size and larger-size patient populations.

The FDA also highlighted other important components of the IRB’s review:

• Assessing the qualifications of the physician submitting the request.
• If the request is for a pediatric patient, confirming that age-appropriate assent is solicited from the patient and permission from a parent or guardian is obtained, as required under 21 C.F.R. § 50.55.
• Confirming that the informed consent form for the treatment includes a statement that explains the investigational nature of the drug and the fact that the FDA has not determined that the drug is safe or effective for use in treating COVID-19. This type of statement will satisfy the requirements of 21 C.F.R. § 50.25(a)(1).

This guidance represents an important effort by the FDA to respond to continuing uncertainty by IRBs as to how to review expanded access requests for treatment of individual patients through the lens of the research approval and informed consent criteria that they are required to apply even though expanded access uses are not research. Although the FDA’s recommendations are intended to remain in effect only for the duration of the COVID-19 public health emergency declared by the U.S. Secretary of Health and Human Services, the FDA indicated that this guidance is expected to assist the FDA more broadly in its continued effort to facilitate patient access to drugs through expanded access beyond the public health emergency, and noted that it reflects the FDA’s general thinking on this issue. As such, within 60 days following the termination of the COVID-19 public health emergency, the FDA intends to revise and replace this guidance based on any comments received and the FDA’s experience with its implementation.

Given the COVID-19 public health emergency, this guidance is being implemented without prior public comment, but it remains subject to comment in accordance with the FDA’s good guidance practices. You may submit a comment on the guidance online by clicking here. You may also mail your written comments to: Dockets Management, Food and Drug Administration, 5630 Fishers Lane, Rm 1061, Rockville, MD 20852. All written comments should be identified with the docket number: FDA-2020-D-1414.

For questions regarding the guidance or the IRB’s role in reviewing expanded access requests, please contact Marylana Saadeh Helou, Emily Fogler, or your regular Verrill attorney.

To learn more about expanded access and related issues, and to access a COVID-19 Expanded Access template that health care providers and drug manufacturers can use to memorialize the circumstances of the provision of an investigational drug for expanded access use, please see our prior alerts and publications here.