“Compassionate use” is the informal, widely used name for what the U.S. Food and Drug Administration formally calls expanded access: a regulatory pathway that lets a patient with a serious or immediately life-threatening disease or condition receive an investigational drug, biologic, or medical device for treatment outside of a clinical trial, when no comparable or satisfactory approved alternative exists. It is a use-authorization mechanism, not a research pathway — the goal is treating one patient (or a defined group of patients), not generating the controlled data a formal clinical trial produces.
For a research administrator, understanding compassionate use matters because it sits directly adjacent to, but is legally and procedurally distinct from, the standard Investigational New Drug (IND) application that authorizes a sponsor’s clinical trial in the first place. This guide covers the regulatory basis, the three expanded-access categories FDA recognizes, how expanded access differs from a standard IND, and how the Right to Try Act functions as a separate, parallel pathway.
Regulatory basis: 21 CFR 312, Subpart I
Expanded access to investigational drugs for treatment use is codified in 21 CFR Part 312, Subpart I. This subpart sets out the general criteria FDA applies to any expanded access request, and separately addresses the mechanics of the three specific categories of expanded access described below. A device-specific compassionate use mechanism exists in parallel under FDA’s investigational device exemption (IDE) framework (21 CFR Part 812), but Subpart I is the drug/biologic-specific regulatory basis and the one most commonly meant by “compassionate use.”
Across all three categories, FDA’s general criteria for granting expanded access require that:
- The patient has a serious or immediately life-threatening disease or condition.
- There is no comparable or satisfactory alternative therapy available to diagnose, monitor, or treat the disease or condition.
- The patient is unable to obtain the investigational product under a clinical trial, or enrollment in a trial is not possible (for example, the trial has closed, the patient does not meet its eligibility criteria, or no trial is geographically accessible).
- The potential patient benefit justifies the potential risks of the treatment, and the risks are not unreasonable given the disease or condition.
- Providing the investigational product for the requested use will not interfere with the clinical trials that could support the product’s development or marketing approval.
The three expanded access categories
FDA organizes expanded access requests into three categories, scaled to how many patients are involved and how the request is initiated:
1. Individual patient expanded access, including emergency use
Covers a single named patient. The physician submits a request (often FDA Form 3926 for non-emergency individual requests) with sponsor agreement to supply the product. A true emergency — where there isn’t time for the standard written submission — can be authorized by telephone or other rapid means by the FDA reviewing official before paperwork is completed, under the emergency-use provisions of this category; the required documentation follows afterward.
2. Intermediate-size patient population access
Covers a defined group of patients, larger than one but smaller than what a full treatment IND would cover — typically patients who share the same disease or condition and for whom there is no other pathway to access. This is common for rare diseases, where a small, identifiable population needs the same investigational product outside of an ongoing trial.
3. Treatment IND or treatment protocol
Covers widespread access for a large population, typically used when an investigational drug has shown promise for a serious or life-threatening condition during trials (often once it has reached a later development stage) and there is a broader patient population that could benefit before formal marketing approval. A treatment IND or treatment protocol is a more involved submission with more extensive obligations for the sponsor, and it more closely resembles a scaled-down version of the ongoing clinical development program than the individual-patient or intermediate-size categories do.
How expanded access differs from a standard IND application
It’s easy to conflate expanded access with the Investigational New Drug (IND) application that authorizes a sponsor’s clinical trial, because both are filed under 21 CFR Part 312 and both authorize human use of an unapproved drug or biologic. The distinction is one of purpose:
- A standard (research) IND exists to generate the controlled safety and efficacy data needed to support eventual marketing approval. The trial protocol defines a research question, endpoints, and a statistical analysis plan; the population is enrolled according to defined inclusion/exclusion criteria designed to answer that question.
- An expanded access IND or protocol exists to treat a patient (or defined population) who cannot access the product through a trial. It does not need to answer a research question, though sponsors are still required to report any adverse events, and safety data collected can, and sometimes does, inform the overall safety picture supporting later approval.
Practically, this means an active clinical trial and an expanded access protocol for the same investigational product can run side by side — FDA’s general criteria specifically require that the expanded access use not interfere with the trials that could support the product’s approval, precisely because both pathways can be open on the same molecule at once.
Charging and cost
Sponsors are permitted, under narrowly defined circumstances, to charge for an investigational product provided through expanded access — recovering direct costs of manufacture is generally permissible, but expanded access is not intended as a revenue mechanism, and any charge is subject to FDA authorization and specific limitations set out in FDA regulation and guidance.
Right to Try: a distinct, parallel pathway
The federal Right to Try Act, enacted in 2018, created a separate pathway that operates outside of, and does not require, FDA’s expanded access process. Where expanded access is an FDA-authorized pathway requiring FDA sign-off (or emergency-use authorization by an FDA official) on a case-by-case basis, Right to Try allows an eligible patient to request an eligible investigational drug directly from the manufacturer without going through FDA at all for that specific request.
To qualify under Right to Try, both the patient and the drug must meet defined criteria:
- Patient eligibility: the patient must have a life-threatening disease or condition, have exhausted approved treatment options, be unable to participate in a clinical trial for the investigational drug, and provide written informed consent.
- Drug eligibility: the drug must have completed a Phase 1 clinical trial, must not be approved or licensed for any use by FDA, and must be under active investigation in an FDA-authorized clinical trial intended to form the basis of a marketing application (its development or approval process cannot be discontinued or on clinical hold).
Manufacturer participation in Right to Try is voluntary — the Act does not compel a manufacturer to supply its investigational product, and many choose to route requests through FDA’s expanded access program instead, in part because expanded access carries a longer track record, more established safety-reporting infrastructure, and (for some sponsors) a clearer sense of how the request will interact with their ongoing regulatory strategy.
Institutional considerations for research administrators
Even though expanded access sits outside the core clinical trial protocol, it carries real institutional obligations. Individual-patient and intermediate-size expanded access typically requires review by the treating institution’s Institutional Review Board (IRB) (a single IRB member may be able to provide expedited concurrence for an emergency use, with full board review to follow), documented informed consent from the patient or their legally authorized representative, and adverse event reporting back to the sponsor and FDA. Sponsors granting expanded access must also maintain records and reporting obligations distinct from — but running alongside — whatever they maintain for their formal clinical trial program on the same product.
Frequently asked questions
Is compassionate use the same thing as expanded access?
Yes — “compassionate use” is the informal, commonly used term; “expanded access” is FDA’s formal regulatory term for the same pathway under 21 CFR Part 312, Subpart I.
Does a patient need to be enrolled in a clinical trial to get compassionate use access?
No. Expanded access exists specifically for patients who cannot access an investigational product through a clinical trial — because none is available to them, they don’t meet a trial’s eligibility criteria, or no trial is running for their condition.
Who decides whether a compassionate use request is approved?
Both FDA and the sponsor (the company or entity holding the IND for the investigational product) must agree. FDA authorizes the expanded access use; the sponsor must independently agree to supply the product, and is not obligated to do so.
How is Right to Try different from FDA’s expanded access program?
Right to Try lets an eligible patient request an eligible investigational drug directly from the manufacturer without an FDA authorization step for that specific request. Expanded access requires FDA authorization (or FDA emergency-use sign-off) as part of the process. Both still require manufacturer/sponsor agreement to supply the product, and neither compels a manufacturer to do so.
Can compassionate use data be used to support FDA approval?
Expanded access is not designed to answer the research question a formal trial answers, but safety data collected during expanded access use must still be reported and can inform the overall safety profile FDA considers. It does not substitute for the controlled efficacy data generated under a standard research IND.
