FDA updates guidance on expanded access for investigational drugs under IND

The US Food and Drug Administration (FDA) has updated its guidance for industry on expanded access to investigational drugs under an investigational new drug (IND) application. The guidance now includes new frequently asked questions about how expanded access should be implemented given new regulatory access and statutory requirements through the 21st Century Cures Act (Cures Act) and FDA Reauthorization Act of 2017 (FDARA).

While the guidance remains largely the same from 2017, FDA added new recommendations for Institutional Review Board (IRB) review, informed consent and new requirements in Cures Act and FDARA to publicly share sponsor policies on evaluating and responding to expanded access requests, the agency said.

“The manufacturer or distributor is required to include their contact information, procedures for submission of expanded access requests, general criteria for evaluation and response, the anticipated time frame for acknowledgement of such requests, and a hyperlink or other reference to the record in ClinicalTrials.gov that contains information about availability of the drug under expanded access,” FDA wrote.

New questions about expanded access

The new guidance adds several questions concerning safeguards for expanded access use, emergency and non-emergency individual patient expanded access, specific information in informed consent documents and how investigators can comply with the requirement to make their expanded access policy readily available to the public.

Answering a question about what safeguards exist in the expanded access use of an investigational drug under IND, FDA said licensed physicians are investigators who administer and dispense these drugs, and they as well as the sponsors are responsible for complying with the requirements associated with expanded access use, such as reporting adverse events and meeting informed consent requirements as well as obtaining an IRB review of expanded access use for the investigational drug. Sponsors are tasked with ensuring investigators are qualified to administer the investigational drug and keeping accurate records that show effective IND expanded access use.

The guidance also added a section on emergency and non-emergency individual patient expanded access IND. For non-emergency expanded access, “FDA intends to allow for waivers of the requirement for review and approval at a convened IRB meeting for individual patient expanded access INDs where the IRB chairperson or another designated IRB member provides concurrence before treatment use begins,” the agency said, while an IRB should be given notice of emergency expanded access within 5 days of a patient beginning an investigational treatment so it can be reviewed by an IRB using its standard operation procedure. A waiver for intermediate and treatment INDs and protocols is “not appropriate” in the view of the agency, FDA said.

FDA clarified in another question that physicians are not required to get local IRB approval if they are participating in an expanded access protocol if the entity they are working with has already obtained IRB review and approval. “A physician associated with an institution should verify that the sponsor has obtained IRB approval of the protocol, and the physician should consult their institution on their policy in these situations. Some institutions may require that their physicians obtain approval from the institution’s IRB as well,” they wrote.

Informed consent regulations require statements that the study “involves research,” and FDA clarified in the guidance that this statement would also be appropriate to include in informed consent documents for expanded access. “As an alternative and given that the drug used under expanded access is investigational, FDA considers a statement in the informed consent document indicating that although the primary use of the drug is for treatment, the drug is investigational and FDA has not determined that the drug is safe or effective for use in treating the disease or condition, to also satisfy the requirement,” they said.

The agency also provided more details on how to make their expanded access policy publicly available. A manufacturer or distributor should post the policy at the start of a Phase 2 or Phase 3 study or 15 days after the investigational drug receives breakthrough therapy designation, whichever is earlier.

“Posting the expanded access policy on its own website will fulfill the requirement of making the policy available to the public. If a pharmaceutical company or the drug manufacturer is developing multiple investigational drugs, it may have one general expanded access policy that applies to all applicable products and should make such general policy publicly available,” FDA wrote. “However, if it has different expanded access policies for different investigational drugs, each expanded access policy should be made publicly available with reference to the products to which the policy applies.”

New informed consent template

FDA’s new guidance adds an informed consent template for investigators to use when treating a patient with an investigational drug under an IND in the expanded access program. The agency noted that the template is not intended to replace the Federal Food, Drug, and Cosmetic Act or Code of Federal Regulations and investigators are still required to fulfill the requirements of these laws.

The informed consent template asks the investigator to provide the name of the condition, state that no other FDA-approved treatment is available, note the product’s investigational nature, explain that the patient is voluntarily participating in the program and write out contact information for staff that the patient can reach out to with questions.

Investigators should also explain the potential benefits, risks and duration of treatment. They should note that there are no alternative treatment options available, list all applicable procedures associated with treatment and provide instances of when the investigator would stop treatment. Investigators should document any costs and potential injuries and explain how the patient’s health information could be used. The informed consent should contain any other important information pertinent to undergoing the investigational treatment, such as what happens if investigators learn of any new health benefits or risks, patient compensation for treatment and links to educational materials.

Guidance

FDA updates guidance on expanded access for investigational drugs under IND

Related topics

Recommended content

Welcome to the new RAPS Digital Experience