FDA Updates Expanded Access Guidance to Streamline Investigational Drug Access for Patients

The U.S. Food and Drug Administration has issued comprehensive updates to its expanded access guidance, providing clearer pathways for patients with serious or life-threatening conditions (search)Search disease to obtain investigational drugs (search)Search drug outside traditional clinical trials. The October 2025 guidance, titled "Expanded Access to Investigational Drugs for Treatment Use—Questions and Answers," replaces the 2017 version and incorporates regulatory requirements added by the 21st Century Cures Act (search)Search term and the FDA Reauthorization Act (search)Search term of 2017.

Three Pathways for Patient Access

The updated guidance confirms that three expanded access pathways remain available for patients who cannot participate in clinical trials. These include individual patient use (including emergency use), intermediate-size population programs, and treatment Investigational New Drug applications or protocols for larger groups. Each request must demonstrate four key criteria: no comparable or satisfactory alternative therapies exist, the potential benefit justifies the potential risk, the use will not interfere with ongoing clinical development, and the patient does not qualify for any ongoing clinical trials.

The guidance clarifies that expanded access submissions may be filed either by the drug developer as the IND sponsor or by a treating physician acting as a sponsor-investigator. Importantly, the sponsor of a treatment IND does not need to be the sponsor of the well-controlled clinical trials for the same drug.

Enhanced Policy Transparency Requirements

A significant update addresses public disclosure requirements for drug developers' expanded access policies. Companies must now publicly post their expanded access policies by the earlier of initiating a Phase 2 or Phase 3 study or within 15 days after receiving a fast track, breakthrough, or regenerative advanced therapy designation. These policies must explain how requests are submitted, reviewed, expected acknowledgement times, and include links to relevant clinicaltrials.gov records.

The guidance notes that while the FDA cannot require drug developers to provide expanded access, the agency has observed increased patient awareness and more frequent, targeted requests due to social media and readily available clinical trial information.

Streamlined Procedures and Documentation

The updated guidance introduces several practical tools to facilitate the expanded access process. A new matrix summarizes various categories of expanded access, including respective waiting times before treatment may begin, IRB review requirements, and other key information. The guidance also provides a single-patient expanded access informed consent template with instructions and example language for each required element.

For physician-initiated requests, the guidance clarifies that physicians may cross-reference a sponsor's existing IND application information to provide required toxicology, chemistry, manufacturing, and controls data. When companies decline to submit their own expanded access protocol, they may support physician-initiated requests by providing a Letter of Authorization, which permits the FDA to rely on the company's underlying IND without disclosing proprietary data to the treating physician.

IRB Review and Safety Considerations

The guidance maintains that expanded access requires prior Institutional Review Board review in accordance with FDA regulations, with exceptions for emergencies when insufficient time exists for prospective IRB review. In emergency situations, treatment can be initiated without IRB review, provided the IRB is notified within five working days of use. The guidance provides new language explaining how investigators may request a waiver from full IRB review using Form 3926, the FDA's Individual Patient Expanded Access IND Application form.

Regarding safety reporting, the guidance emphasizes that investigators remain responsible for reporting adverse events to sponsors, while sponsors must comply with IND safety reporting requirements. The FDA acknowledges that expanded access data, including safety data, rarely alter approval decisions or result in clinical holds due to adverse events, recognizing that patients receiving drugs through expanded access often have more advanced disease stages than clinical trial participants.

Strategic Implications for Drug Developers

The guidance underscores the need for drug developers to align regulatory actions with patent and exclusivity strategies, particularly when investigational data from expanded access programs could predict future filings. Companies are advised to ensure core patent applications covering composition, methods of use, and formulations are filed before initiating expanded access use to avoid inadvertent public disclosures that could compromise patentability.

The FDA's updated guidance aims to facilitate patient access while ensuring that expanded access programs do not undermine clinical trials, particularly in rare disease settings where patient populations are limited. The guidance provides drug developers with a clearer framework for structuring requests, managing adverse event reporting, coordinating with treating physicians, and planning for appropriate oversight.