Background
The US FDA has a long history of facilitating expanded access (EA) to promising new investigational drugs for patients suffering from serious or life-threatening conditions who have no viable alternative treatment options available to them. In 2009, the agency released regulations on expanded access use under an investigational new drug application (IND) (21 CFR part 312, subpart I). After receiving ongoing questions regarding the implementation of these regulatory requirements, the FDA released a guidance document, in 2017, which provided recommendations for key stakeholders in a question-and-answer format.
Since then, the FDA has received additional questions, many of which reference the regulatory requirements added by the 21st Century Cures Act (Cures Act) and the FDA Reauthorization Act of 2017 (FDARA). To address these questions, the FDA has now finalized its updated guidance document: Expanded Access to Investigational Drugs for Treatment Use – Questions and Answers, which replaces the 2017 version. The new Q&A document, released in October 2025, keeps the core EA framework intact but provides clearer structure, explicit IRB and consent pathways, and practical tables and templates that speed decision-making.
Below, we break down the meaningful differences from the 2017 version and how Sponsors can operationalize the updates to move from request to first-patient dosed, while keeping compliance at the forefront.
What Did Not Change
To start, it is worth mentioning some key elements that have remained the same to re-emphasize their importance.
- The three EA categories remain: single-patient, intermediate-size, and treatment IND/protocol.
- The statutory criteria in 21 CFR part 312, Subpart I still apply: serious disease/condition, no comparable alternative, potential benefit justifies potential risks, and providing the drug will not interfere with clinical development.
- FDA still cannot enforce access. The Sponsor’s willingness to provide drug supply is the gating factor.
What Has Changed vs. 2017 (in simple terms)
1) Cleaner Structure, operational appendices
The new guidance is still a Q&A, but has been reorganized for faster navigation and adds two practical appendices:
- Appendix A – a one-page matrix that lays out waiting periods, IRB requirements, and who files what for each EA route (single-patient, intermediate-size, treatment IND/protocol; emergency vs. non-emergency).
- Appendix B – a single-patient EA informed consent template. Many investigators asked for this; having an FDA template reduces back-and-forth with IRBs and helps align language with 21 CFR part 50.
2) Informed consent expectations are more practical
The guidance reiterates that EA uses are clinical investigations under 21 CFR part 50, but it goes further than 2017 by offering practical wording and an FDA template. It clarifies how to meet the “research” disclosure requirement when a traditional study description doesn’t fit and underscores the need to tell patients the drug is investigational and not established as safe/effective for the requested use. Net result: less ambiguity for physicians and IRBs, leading to faster approvals.
3) IRB review pathway for non‑emergency single‑patient EA is clarified
The 2017 guidance document introduced Form FDA 3926 and the option to proceed with IRB chair (or designee) concurrence in lieu of a full board meeting. The new Q&A keeps that option and spells out the mechanics more clearly, including how checking Field 10.b on Form 3926 functions as the waiver request, what documentation the IRB must keep, and how to handle amendments and continuing review. For Sponsors and sites, this route saves days to weeks versus waiting for a convened IRB.
4) Timing rules are easier to apply
The rules themselves didn’t change, however, the document now makes it easier to see when the 30‑day safety review clock applies (e.g., a brand-new EA IND) versus when treatment may start upon FDA acknowledgement (e.g., adding an intermediate-size expanded access protocol to an active IND) while still meeting IRB obligations. For busy medical, regulatory, and clinical operations teams, this consolidated view reduces cycle time.
5) Multi‑drug requests and chronic therapy
The new guidance reaffirms that one EA submission can, when clinically appropriate, cover multiple investigational drugs and that multi‑course or chronic therapy may be authorized if dosing, duration, and monitoring are well defined and supported by safety information. These concepts existed before but are easier to discover and operationalize now.
6) Public posting requirements are made explicit
7) Sponsor/physician roles and cross‑referencing
Clearer language exists around letters of authorization (LOAs). For example, information that may be cross‑referenced (CMC, tox, manufacturing), and details on what a physician needs to submit if the manufacturer refuses to authorize cross‑reference(s). This is useful for Sponsor‑investigators and for manufacturers fielding direct physician requests.
8) Public posting requirements are made explicit
The Q&A consolidates the mechanics around emergency use: telephone authorization, written follow‑up timelines, and IRB notification. Nothing revolutionary, but the reminders live next to the practical tables and forms, which elevates consistency for sites.
Operational Implications for Sponsors (and How WEP Clinical Helps)
1) Make the IRB chair pathway your default for eligible single‑patient EA
When a request is non‑emergency, use Form FDA 3926 and check Field 10.b to document the request for IRB chair (or designee) review. Build this into SOPs, training, and site kits. WEP standardizes this in our EAP playbook so investigators have step‑by‑step guidance, template emails to IRBs, and a checklist for required attachments. Result: fewer holds, fewer resubmissions, faster starts.
2) Adopt the FDA informed consent template and tailor once
Start from Appendix B and tune for product‑specific risks, local regulations, and reading level. WEP’s Project Managers – with oversight from medical and regulatory affairs teams – align the template with the Sponsor’s safety language, device/combination product nuances (if applicable), and in simple, easy to understand language. This approach reduces IRB queries and shortens approval cycles – especially when multiple sites are involved.
3) Tighten your public EA policy and timing
Update your corporate website with a clear, searchable EA policy that meets content and timing expectations. Align your ClinicalTrials.gov entries and linkages to eliminate contradictions. WEP partners with Sponsor communication and regulatory teams to implement the right pattern (on‑site page, PDF, or CT.gov link) and set reminders keyed to development milestones.
4) Choose the right pathway early
If single‑patient requests start to accumulate, consider moving to an intermediate‑size EA protocol under your active IND. That consolidates oversight, standardizes monitoring and safety reporting, and reduces one‑off paperwork and potential IRB friction. WEP designs and runs these protocols with the same discipline we bring to interventional trials: data collection plans, safety management, home‑nursing options, logistics, and partnership governance.
5) Plan for combinations and chronic dosing
Where medically appropriate, write the EA request to cover combination therapy and/or multi‑course/chronic use. The key is specificity: dosing, duration, criteria for continuation, and safety monitoring. WEP works with Sponsor medical and safety teams to craft robust rationales that satisfy FDA expectations while keeping real‑world delivery feasible.
6) Streamline emergency use response
Emergency use is rare but time‑critical. WEP maintains an EA rapid‑response workflow with 24/7 on‑call medical and regulatory support, scripted call trees for FDA contact, and pre‑built documentation packets for the required follow‑ups. This prevents last‑minute scrambles and reduces the risk of non‑compliance under pressure.
EA Delivery is Cross‑Functional – Teamwork is Critical
Expanded Access is not a single form process. At WEP, we tell our Sponsors to think of EA more like an ‘Expanded Access Clinical Trial’ that may touch medical, regulatory, clinical operations, safety/pharmacovigilance, manufacturing/supply chain, QA, legal, and communication teams within their organization. Although involvement may be limited within some of the cross-functional teams listed, it’s important to note their potential involvement in the first instance to set the tone of the program. Sponsors that treat EA like a cross‑functional program, not a one‑off exception, will move faster and reduce risk.
How to ensure your team is understanding and implementing these changes :
While this new guidance document was finalized recently, WEP has been following this guidance since it was initially drafted by the FDA. As such, our regulatory team has already been guiding our clients through these changes to ensure they are working efficiently and designing and delivering compliant, operationally-sound Expanded Access Programs.
📩 If you would like to connect to discuss how we can support your team, please reach out to us – EAP@WEPCLINICAL.COM
