FDA Further Expands And Clarifies Expanded Access FAQs

By Dianne J. Bourque, partner, Holland & Knight

In October 2025, the FDA published updates to its expanded access guidance (the guidance) to assist research sponsors, researchers, IRBs, and others with the implementation of FDA’s expanded access regulations.

The guidance, which replaces the FDA’s 2017 expanded access guidance, is presented in the same question and answer format as the 2017 guidance, addressing frequently asked questions and clarifying issues arising since 2017, including regulatory requirements added by the 21^st Century Cures Act¹ and the FDA Reauthorization Act of 2017.² It also includes new tables and an informed consent template.

The updated guidance presents a great opportunity for sponsors to review their expanded access programs to ensure compliance with regulatory requirements and readiness for an expanded access request.

Expanded Access Background

Expanded access, which is also referred to as “compassionate use,” is the treatment use of an investigational drug or a drug not yet approved for marketing. The FDA has long facilitated expanded access requests for patients with serious or immediately life-threatening diseases or conditions who have no available treatment alternatives. In our experience, the FDA appreciates the unfortunate clinical circumstances that might prompt a physician to request expanded access to an investigational product. We have seen the FDA respond to expanded access requests at night and during the weekends, and overwhelmingly, the FDA has supported patients who meet expanded access criteria.

The FDA permits expanded access for individual patients, including in an emergency, but there is also an expanded access pathway for intermediate-sized patient populations and treatment IND protocols for broader use. The guidance describes requirements for each of these categories of expanded access. Importantly, expanded access to an investigational drug is only available when the sponsor of that investigational drug agrees to provide expanded access. The FDA cannot force a sponsor to provide access to the investigational drug. The FDA does, however, require that a sponsor make its policy for responding to expanded access requests publicly and readily available, such as by posting on a public-facing website.³ As the guidance makes clear, expanded access policies must be posted by the earlier of 1) initiation of a Phase 2 or 3 study; or 2) within 15 days after the drug receives a Fast Track, Breakthrough, or Regenerative Medicine Advanced Therapy designation.

A sponsor’s expanded access policy should explain how requests for expanded access are submitted, how they are reviewed, the expected acknowledgement time, and a link to the relevant clinicaltrials.gov record, as applicable. Of course, if a sponsor opts not to make its investigational product available for expanded access use, the expanded access policy should indicate that expanded access is not available.

With the advent of social media and the availability of clinical trials information, such as through clinicaltrials.gov, patients are more educated about drug product pipelines than ever. And in our experience, they are making more frequent, targeted, and in some cases aggressive expanded access requests, so it’s important for sponsors to be prepared for the inevitable request.

Expanded Access Roles And Responsibilities

Expanded access requests most often come from treating physicians or investigators with patients who fit expanded access criteria, i.e., the patient is at a stage of disease in which there is a reasonable likelihood that death will occur within a matter of months or premature death is likely without treatment, but the patient is not qualified to join a clinical trial for the relevant investigational product. The guidance now offers new clarification on physician and sponsor roles in an expanded access request. For example, the guidance clarifies that a physician may cross-reference a sponsor’s existing IND application information for submission with the expanded access request in order to provide toxicology, chemistry, manufacturing, and controls or other required information. The guidance also describes what a physician must submit if the sponsor does not permit cross-reference.

IRB Review

An important expanded access requirement is IRB review, which is the physician’s responsibility. With some exceptions, expanded access requires prior IRB review in accordance with FDA regulations in 21 CFR Part 56. The exception is for emergencies when there is insufficient time to secure prospective IRB review. In an emergency, treatment can be initiated without IRB review, provided that the IRB is notified of the emergency expanded access use within five working days of the use.⁴ In 2017, the FDA made clear that an investigator may request review of a proposed expanded access use by the IRB chair (or designated IRB member) instead of the full IRB at a convened meeting. The guidance provides new language explaining how an investigator may request a waiver from full IRB review on Form 3926, which is the FDA’s Individual Patient Expanded Access IND Application form. The guidance also describes required IRB documentation, amendments, and continuing review requirements.

New Expanded Access Categories Appendix

The guidance introduces a helpful matrix that summarizes the various categories of expanded access, including their respective waiting times before treatment may begin, IRB review requirements, and other key information. The matrix is a helpful, quick reference for investigators.

New Informed Consent Appendix

Another new appendix to the guidance is the single-patient expanded access informed consent template, which includes instructions for creating an expanded access consent and example language for each required element. In the clinical research context, it can be difficult to ensure that study participants appreciate the nature of research — i.e., that it’s not treatment and that it could potentially harm as well as help a participant. This distinction is even more difficult to make in the expanded access context because an investigational product is being used for treatment purposes. The guidance includes help with consent wording and explains how to address required disclosures regarding the investigational nature of a product when it’s being used in a treatment context.

The consent template also addresses topics, such as who pays for treatment. For example, it provides sample language that states, “If you receive this treatment, your insurance may not cover the cost of some of the tests and visits to see your doctor that are related to receiving the investigational drug. Contact your insurance company to learn more about the coverage if you decide to receive the treatment.” It also includes example language addressing injury: “Costs related to treatment-related injuries will be billed in the ordinary manner to you or your insurance company.”

Safety Reporting

Safety reporting is an important part of the expanded access pathway. Investigators are responsible for reporting adverse events to sponsors. Sponsors are responsible for complying with IND safety reporting requirements⁵, meeting annual reporting requirements⁶, ensuring that treating physicians are licensed and qualified to administer the investigational drug for expanded access use, providing physicians with the information needed to minimize risk and maximize potential benefits, and maintaining adequate drug disposition records.⁷ The guidance notes that expanded access data, including safety data, rarely alter approval decisions or result in a clinical hold due to adverse events observed in expanded access treatment. Patients who receive a drug through expanded access often have a more advanced stage of disease than patients participating in a clinical trial, and they may be receiving other therapies for their disease at the same time they are receiving a product through expanded access. The FDA recognizes that these and other factors make it difficult to attribute an adverse event to expanded access treatment.

Additional Guidance

The guidance includes new information to help providers, patients, and others learn about drug companies’ expanded access policies with a link to the FDA Reagan-Udall Foundation’s Expanded Access Navigator website. The website includes extensive information about expanded access, including a list of drug companies and their expanded access policies.

References:

1. 21st Century Cures Act, Public Law 114-255; 130 STAT.1033, December 13, 2016, Sec. 3032
2. FDA Reauthorization Act of 2017 (FDARA), Public Law 115-52; 131 STATE.1005, August 18, 2017, Sec. 610
3. 21 USC 360bbb-0(b)
4. 21 CFR 56.104(c)
5. 21 CFR 312.32
6. 21 CFR 312.22
7. 21 CFR 312.57

About The Author:

Dianne Bourque is a healthcare attorney in Holland & Knight's Boston office who focuses on the Health Insurance Portability and Accountability Act (HIPAA) as well as clinical research and life sciences regulatory issues.

A large part of Ms. Bourque's practice involves counseling researchers and research sponsors in matters related to the FDA and Office for Human Research Protections (OHRP) regulated clinical research, including consent, access to and use of tissue and associated patient information, expanded access to investigational products, and the IRB process.

Ms. Bourque advises a variety of healthcare industry clients on a broad range of regulatory issues, including data acquisition and use in AI algorithm training, research, product development, and digital health applications. She also advises providers on risk management and patient care matters.