Compassionate Use Programmes for Sponsors: Scope and Obligations

A compassionate use programme makes an investigational medicine available outside clinical trials to seriously ill patients with no satisfactory authorised alternative. For the sponsor it brings obligations of its own: fair patient selection, supply allocation that protects ongoing trials, full pharmacovigilance, cost recovery rules and a plan for continuity of care when the programme ends. In the EU the framework is Article 83 of Regulation (EC) No 726/2004 plus national rules; in the US it is FDA expanded access.

When a patient faces a life-threatening condition and no approved therapy exists, the moral imperative to provide access to an investigational drug becomes acute. For pharmaceutical sponsors, this imperative carries with it a complex web of regulatory, ethical and operational obligations that extend far beyond simply shipping product. Understanding the scope of compassionate use programmes, the requests that trigger them and the obligations sponsors must fulfil is essential to maintaining both compliance and public trust. The regulatory environment in 2026 reflects years of evolving guidance from the FDA, the EMA and national competent authorities, each layering distinct requirements onto sponsors who choose to make unapproved medicines available. Two recent examples are the FDA's revised questions-and-answers guidance on expanded access, issued in April 2026 (U.S. Food and Drug Administration, 2026b), and France's decree harmonising early and compassionate access, in force since 1 September 2026 (Décret n° 2026-448). This article addresses the full arc of sponsor responsibility: from defining what compassionate use means in practice, through the regulatory frameworks that govern it, to the strategic and ethical decisions that shape every programme's success or failure.

What counts as a compassionate use medicine?

Compassionate use medicines are investigational products made available outside of clinical trials to patients who have exhausted all other treatment options. What is compassionate use in legal terms? In the EU, Article 83 of Regulation (EC) No 726/2004 defines it as making a medicine available, for compassionate reasons, to a group of patients with a chronically or seriously debilitating disease, or a disease considered to be life-threatening, who cannot be treated satisfactorily by an authorised medicinal product; the medicine must be the subject of a marketing authorisation application or be undergoing clinical trials (Regulation (EC) No 726/2004). The CHMP guideline on compassionate use reads “cannot be treated satisfactorily” as covering patients left without treatment options, patients whose disease does not respond or relapses, and patients for whom the available treatments are contraindicated or inadequate (European Medicines Agency, 2007). In the US, the FDA's expanded access page describes expanded access, sometimes called compassionate use, as a pathway for a patient with a serious or immediately life-threatening disease or condition to gain access to an investigational product for treatment outside clinical trials when no comparable or satisfactory alternative therapy is available (U.S. Food and Drug Administration, 2026a).

The scope of these programmes varies by jurisdiction, but the underlying principle is consistent: a seriously or terminally ill patient should not be denied access to an investigational medicine solely because it has not yet received a marketing authorisation. The principle has a limit that both regulators state plainly. Clinical trials come first, and patients should always be considered for inclusion in a trial before compassionate use is offered (European Medicines Agency, 2007; U.S. Food and Drug Administration, 2024b). For sponsors, the scope of a compassionate use programme defines who qualifies, under what conditions the drug is supplied and what data must be collected throughout the process.

Compassionate use is also distinct from supply for a single named patient, which a physician obtains from the manufacturer under their own direct responsibility and which the EMA says should not be confused with compassionate use programmes (European Medicines Agency, 2010). For the wider family of pre-authorisation routes, our overview of what a managed access programme is shows how the routes fit together.

What are the core objectives of expanded access and compassionate use programmes?

A compassionate use programme serves several interlocking purposes. First, it fulfils a humanitarian obligation by providing access to patients with no alternatives (Regulation (EC) No 726/2004). Second, it collects safety information under defined conditions, which the sponsor must report and which regulators can consider alongside trial data, although such programmes cannot replace clinical trials (Decreto 7 settembre 2017; European Medicines Agency, 2007). Third, it gives treating physicians and the sponsor's own medical and supply teams practical experience of supplying, administering and monitoring the medicine under a protocol. That experience must stay outside any promotional activity: in the EU a medicine without a marketing authorisation may not be advertised, and in the US a sponsor may not represent an investigational drug as safe or effective for the use under investigation (Directive 2001/83/EC; 21 C.F.R. § 312.7, 2026). Sponsors should view these objectives not as competing priorities but as mutually reinforcing elements of a responsible access strategy.

Mapping the variation is the first job. Building and staffing the infrastructure to run against it, country by country, is the harder one. Ideogen handles the national filings, the import and supply route, physician request handling and the safety reporting for partners across Europe, MENA, CIS and 94 markets worldwide, in orphan and rare disease. Talk to our experts to bridge market access on rare and orhpan disease to meet unmet needs and improve patient outcomes at [email protected].

How does compassionate use differ from a clinical trial?

Compassionate use exists to benefit the individual patient, not to generate generalisable evidence.

Clinical trials are designed to answer specific scientific questions under controlled conditions, with predefined endpoints, inclusion criteria and statistical plans. Compassionate use programmes, by contrast, exist primarily to benefit the individual patient rather than to generate generalisable evidence. The CHMP is explicit that clinical trials are practically the only means of obtaining reliable and interpretable efficacy and safety data, and that compassionate use is not a substitute for properly conducted trials (European Medicines Agency, 2007). The regulatory burden differs accordingly: informed consent is still required (21 C.F.R. § 312.305, 2026), but the protocol is typically less rigid, endpoints are not formally analysed, and the patient population may include individuals who would be excluded from a trial, for example because they do not meet its enrolment criteria or cannot reach a trial site (21 C.F.R. pt. 312, subpt. I, 2026). Sponsors must be careful not to conflate the two, as blurring the line can create regulatory risk and undermine the integrity of both the trial and the access programme. In the US, for instance, supplying an investigational drug for treatment to a patient who is not enrolled in a trial counts as expanded access and needs its own submission (U.S. Food and Drug Administration, 2026b).

What do the FDA and the EMA require of sponsors?

In the US, the FDA requires an expanded access submission under 21 CFR 312, Subpart I, and IND safety reporting by the sponsor (21 C.F.R. pt. 312, subpt. I, 2026; 21 C.F.R. § 312.305, 2026). In the EU, Article 83 of Regulation (EC) No 726/2004 sets the framework, and each Member State sets its own procedures and reporting obligations (European Medicines Agency, 2007; Regulation (EC) No 726/2004).

The two most influential regulatory bodies governing compassionate use are the U.S. Food and Drug Administration and the European Medicines Agency. Each has established distinct pathways, timelines and documentation requirements that sponsors must understand in detail before initiating any programme. Their roles also differ in kind. The FDA must find that its criteria are met before any expanded access use proceeds (21 C.F.R. § 312.305, 2026), whereas the EMA's scientific committee gives recommendations that do not create a legal framework, and the Member States coordinate and implement programmes under their own rules and procedures (European Medicines Agency, 2020).

How do the FDA's expanded access pathways and IND submissions work?

The FDA offers three categories of expanded access under 21 CFR 312, Subpart I: individual patient access (including emergency use), intermediate-size patient populations, and treatment protocols for widespread use (21 C.F.R. pt. 312, subpt. I, 2026; U.S. Food and Drug Administration, 2026a, 2026b). Each category needs an expanded access submission, which may be a new IND or a protocol amendment to an existing IND (21 C.F.R. § 312.305, 2026). When a treating physician files the submission, the sponsor can grant a right of reference, given in a letter of authorisation, that lets the FDA refer to information in the sponsor's own IND (21 C.F.R. § 312.310, 2026; U.S. Food and Drug Administration, 2026b). Emergency IND requests can be authorised by telephone, with written follow-up within 15 working days (21 C.F.R. § 312.310, 2026). Approval rates exceed 99 per cent for individual patient requests (U.S. Food and Drug Administration, 2024a, 2025).

In April 2026, the FDA issued a second revision of its questions-and-answers guidance on expanded access. Among other points, it sets out which forms suit each type of submission, how IRB review works for individual patients, and the follow-up the agency expects from sponsors: IND safety reports, annual reports for uses that last a year or longer, and a written summary at the end of individual patient treatment (U.S. Food and Drug Administration, 2026b). The volume of requests is substantial. According to the FDA's submission data, its Center for Drug Evaluation and Research received 1,326 non-emergency and 634 emergency individual patient expanded access INDs in fiscal year 2023, and allowed 1,318 and 634 of them to proceed (U.S. Food and Drug Administration, 2024a). Providing access remains voluntary: the FDA can authorise expanded access but cannot compel a sponsor to supply its drug (U.S. Food and Drug Administration, 2026b). The table summarises the three categories (21 C.F.R. pt. 312, subpt. I, 2026).

How does Article 83 work, and how do Member States differ?

Under Article 83 of Regulation (EC) No 726/2004, the EMA can issue opinions recommending compassionate use for products undergoing centralised marketing authorisation review or under clinical investigation (European Medicines Agency, 2007; Regulation (EC) No 726/2004). However, implementation remains the responsibility of individual EU Member States, which means sponsors face a patchwork of national requirements. A Member State that makes a medicine available under Article 83 notifies the EMA, and the Committee for Medicinal Products for Human Use (CHMP), after consulting the manufacturer or the applicant, may adopt opinions on the conditions for use, the conditions for distribution and the patients targeted (Regulation (EC) No 726/2004). Companies should not ask the EMA for an opinion directly, although they may inform it of national procedures under way (European Medicines Agency, 2007). Such opinions are rare: the EMA's public list holds six, the most recent adopted in 2020 (European Medicines Agency, 2020), while a policy analysis of seven European countries identified 36 compassionate use programmes for anticancer and orphan medicines authorised in 2021 and 2022 alone (Rosenberg et al., 2025).

France's Autorisation d'Accès Compassionnel (Agence nationale de sécurité du médicament et des produits de santé, 2026; Décret n° 2026-448), Germany's compassionate use programmes under Section 21(2) no. 3 of the German Medicinal Products Act (AMG) with the Arzneimittel-Härtefall-Verordnung (AMHV) (Arzneimittel-Härtefall-Verordnung, 2010), and Italy's Decreto Ministeriale 7 September 2017 (Decreto 7 settembre 2017) each impose distinct procedural and reporting obligations. An individual healing attempt (individueller Heilversuch) is a different, physician-level concept: the AMHV does not apply to the use of an unauthorised medicine in a single patient under a physician's direct responsibility (Arzneimittel-Härtefall-Verordnung, 2010). Sponsors operating across multiple Member States must map these variations early and build compliance infrastructure that accounts for differing timelines, physician request procedures and pharmacovigilance standards. The table compares the three frameworks on the points that most often shape a programme plan.

What does the Right to Try Act change for sponsors?

In the United States, the Right to Try Act, signed into law in 2018 (Right to Try Act, 2018; U.S. Food and Drug Administration, 2018), created an alternative pathway that bypasses FDA review for certain eligible patients (U.S. Food and Drug Administration, 2024c). According to the FDA's Right to Try page, an eligible patient has a life-threatening disease or condition, has exhausted approved treatment options, cannot take part in a clinical trial of the drug and has given written informed consent; an eligible drug has completed a Phase 1 trial, is not approved for any use and remains in active development under an IND (U.S. Food and Drug Administration, 2024c). The FDA does not review or approve Right to Try requests, individual requests do not need IRB review, and the sponsor reports to the agency through an annual summary of use that includes serious adverse events (U.S. Food and Drug Administration, 2024c).

Sponsors are not required to participate in Right to Try requests: the Act does not oblige a sponsor to provide an eligible drug, and no liability lies against a sponsor for deciding not to provide one (Right to Try Act, 2018; U.S. Food and Drug Administration, 2024c). For a drug provided in compliance with the Act, it states that no liability in a cause of action lies against a sponsor or manufacturer, or against a prescriber, dispenser or other entity, unless the relevant conduct constitutes reckless or wilful misconduct, gross negligence or an intentional tort under state law (Right to Try Act, 2018). These protections are not absolute: beyond these provisions, the Act leaves product liability, tort, consumer protection and warranty actions unaffected (Right to Try Act, 2018). In practice, the route has seen little use. The FDA's consolidated annual summary counts 12 eligible drugs and biological products for the first reporting period, from 30 May 2018 to 31 December 2022, then four, five and six for 2023, 2024 and 2025, and records no case in which Right to Try outcome data were used in a review (U.S. Food and Drug Administration, 2026d). In a qualitative study of 21 oncologists experienced in expanded access, none had formally tried to obtain a drug through Right to Try (Smith et al., 2021). Expanded access keeps FDA review, IRB oversight and defined reporting duties, which gives sponsors clearer regulatory oversight and better-defined obligations. Understanding where liability begins and ends under each pathway is critical for any sponsor evaluating whether and how to establish a compassionate use programme.

What obligations does a sponsor take on when it runs a programme?

Once a sponsor commits to providing pre-approval access, a cascade of operational obligations follows. These obligations span patient selection, supply logistics and safety monitoring, and each must be managed with the same rigour applied to a clinical trial. In the US this is a legal duty as much as good practice: whoever submits an expanded access IND or protocol is a sponsor under FDA rules and carries the sponsor responsibilities set out for clinical investigations, to the extent they apply (21 C.F.R. § 312.305, 2026).

How should sponsors select patients fairly?

Patient selection is among the most ethically sensitive aspects of any compassionate use programme. Sponsors must define eligibility criteria that balance medical need against the availability of drug supply, the stage of clinical development and the risk-benefit profile for the individual patient. Criteria should be documented, publicly accessible where feasible, and applied consistently. In the US, a manufacturer of an investigational drug for a serious disease must publish its expanded access policy, including the general criteria it uses to evaluate requests, by the first Phase 2 or Phase 3 study at the latest (21 U.S.C. § 360bbb-0, 2024). Compliance has been uneven: one analysis found a public policy at 32 per cent (140 of 423) of applicable US companies with an oncology drug (Kang et al., 2021). Some sponsors have used independent review committees to evaluate requests, removing the decision from commercial teams and reducing the perception of bias. In one published pilot, a company and an academic ethics department set up a committee of medical experts, bioethicists and patient representatives to allocate a scarce investigational oncology agent to single patients (Caplan et al., 2018). Transparency in this process is not merely a regulatory expectation; it is a reputational necessity.

How should sponsors manage supply and allocate the drug?

Providing investigational product outside of clinical trials introduces direct tension with the supply needed for ongoing studies, and regulators look at the same tension. Before authorising any expanded access, the FDA must determine that it will not interfere with the clinical investigations that could support approval (21 C.F.R. § 312.305, 2026), and the CHMP warns that compassionate use should not slow down the trials that provide essential benefit-risk information (European Medicines Agency, 2007). Sponsors must forecast demand for compassionate use alongside trial enrolment projections, manufacturing capacity and shelf-life constraints. A well-designed allocation strategy addresses several questions simultaneously:

• How much product can be diverted from clinical supply without jeopardising trial timelines?
• What happens if demand for compassionate access exceeds available inventory?
• Are there geographic or logistical barriers to shipping investigational product to certain regions?
• What cold chain or special handling requirements apply?

Failure to plan for these contingencies can delay access for patients and, in worst-case scenarios, compromise the clinical programme that the compassionate use effort is intended to complement. The FDA notes that the risk of interference is highest early in development and in rare diseases, where even a series of individual requests could affect a development programme (U.S. Food and Drug Administration, 2026b).

Who reports adverse events, and how fast?

Sponsors bear full responsibility for collecting, evaluating and reporting adverse events arising from compassionate use. Under FDA regulations, sponsors must report serious and unexpected suspected adverse reactions within 15 calendar days, and unexpected fatal or life-threatening suspected adverse reactions within 7 calendar days (21 C.F.R. § 312.32, 2026; 21 C.F.R. § 312.305, 2026). In the EU, national rules set the detail, and the timelines differ. Where the CHMP has adopted an opinion, the Regulation's pharmacovigilance rules for centrally authorised medicines also apply to the programme (European Medicines Agency, 2007). In Germany, the person responsible for a programme must report each suspected serious adverse reaction to the competent federal authority electronically, within 15 days at the latest, and submit a safety report when the programme ends (Arzneimittel-Härtefall-Verordnung, 2010). In Italy, physicians must report suspected adverse reactions within two days, or 36 hours for biological medicines, and the supplying company then manages the reports under the national pharmacovigilance rules (Decreto 7 settembre 2017).

Sponsors must ensure that treating physicians understand their obligation to report adverse events promptly and that internal pharmacovigilance teams have the capacity to process reports from what can be a geographically dispersed and clinically heterogeneous patient population. The quality of safety data from compassionate use can influence regulatory decisions about the product's eventual approval, although such effects are rare. The FDA reports a small number of cases in which expanded access safety data helped assess a drug's risks and benefits, and a very small number in which adverse event information contributed to approved labelling (U.S. Food and Drug Administration, 2026b). In ten years of records at the FDA's drug centre, 0.2 per cent of commercial development programmes were placed on clinical hold because of adverse events in expanded access patients, against 7.9 per cent placed on hold for any reason (Jarow et al., 2016).

The systems behind these duties are covered in our guide to pharmacovigilance in access programmes.

What ethical and practical challenges do sponsors face?

The main ones are protecting recruitment into the trials that must show safety and efficacy, and paying for supply: charging rules limit cost recovery, and national health systems do not consistently reimburse unapproved products (Rosenberg et al., 2025).

Beyond regulatory compliance, sponsors face a set of ethical and practical dilemmas that require careful judgement and, often, difficult trade-offs.

How can sponsors balance pre-approval access with trial recruitment?

Sponsors can limit compassionate use to patients who are ineligible for existing trials, or limit it by region or by timing, and should document each of these judgement calls for ethics committee review.

One of the most persistent tensions in compassionate use is the risk that providing free access to an investigational drug will undermine enrolment in the very trials needed to demonstrate its safety and efficacy. If patients can obtain the drug outside of a trial, some may decline to participate in a randomised study, particularly one that includes a placebo arm. The FDA regards programmes that treat larger populations as having a high potential to interfere with recruitment, and expects patients who receive a drug under expanded access generally to be ineligible for, or otherwise unable to enter, ongoing trials (U.S. Food and Drug Administration, 2026b). Sponsors must weigh this risk against the ethical obligation to treat patients who cannot wait for trial results. Strategies to mitigate this tension include restricting compassionate use to patients who are ineligible for existing trials, limiting access geographically, or timing programme launches to coincide with trial completion milestones. None of these solutions is perfect, and each involves judgement calls that should be documented and reviewed by ethics committees.

Can a sponsor charge for a compassionate use medicine?

The FDA permits sponsors to charge for investigational drugs provided under expanded access, but only with its prior written authorisation and only to recover direct costs: the cost per unit to manufacture or acquire the drug, and the direct costs of shipping and handling it (21 C.F.R. § 312.8, 2026). For intermediate-size and treatment use, the sponsor may also recover the costs of monitoring, of complying with IND reporting requirements and other administrative costs directly associated with the expanded access IND. Indirect costs, such as research and development, are excluded, so charging cannot turn a profit, and the calculation must be reviewed and approved by an independent certified public accountant (21 C.F.R. § 312.8, 2026).

In the EU, Article 83 itself does not regulate charging, and the rules are national (Regulation (EC) No 726/2004). In Germany, medicines in a compassionate use programme are supplied free of charge under Section 21 AMG (Arzneimittelgesetz, 2005, § 21), and Italy defines compassionate use as supply free of charge by the company (Decreto 7 settembre 2017). In France, the ANSM states that cover by the national health insurance is guaranteed automatically for medicines under compassionate access (Agence nationale de sécurité du médicament et des produits de santé, 2026). Comparative studies confirm the spread: a comparison of France, Italy, Spain and the UK found that compassionate use is usually paid for by the company, while other early access programmes are reimbursed by third-party payers (Tarantola et al., 2023), and reimbursement options for compassionate use and named patient supply are inconsistent between countries (Rosenberg et al., 2025). For sponsors, the financial burden of a large compassionate use programme can be substantial, particularly for biologics or gene therapies with high per-unit production costs. Sponsors should model the financial impact of compassionate use early in clinical development and build these costs into programme budgets rather than treating them as an afterthought.

Why do programme data and patient transitions matter to sponsors?

The data generated by compassionate use programmes, and the transition of patients out of those programmes, represent both an opportunity and an obligation for sponsors.

Can real-world evidence from compassionate use support regulatory submissions?

Safety and efficacy observations from compassionate use can supplement clinical trial data, particularly for rare diseases where trial enrolment is limited. Both regulators have committed to using real-world evidence more: the FDA created a framework in 2018 for evaluating its use in regulatory decisions (U.S. Food and Drug Administration, 2026c), and the EMA and the European medicines regulatory network are working to integrate real-world data and evidence into regulatory decisions (European Medicines Agency, 2026). A review of FDA and EMA approval documents found 39 approvals in which data from expanded access programmes informed the assessment of clinical efficacy, 13 of them as the main evidence (Polak et al., 2020). Italian law states the boundary from the other side: data from compassionate use do not replace the data needed for a marketing authorisation, but may be used to support it (Decreto 7 settembre 2017). Sponsors who invest in standardised data collection, electronic case report forms and consistent follow-up schedules position themselves to make full use of the data these programmes generate. The caveat is that compassionate use data is inherently uncontrolled, and regulators will scrutinise its quality and completeness with appropriate scepticism.

What happens to patients when the programme ends?

When a compassionate use programme ends, whether because the product receives marketing authorisation, the sponsor discontinues development, or supply is exhausted, patients who have been receiving the drug face an abrupt transition. Sponsors have an ethical and, in some jurisdictions, a legal obligation to plan for this eventuality. In the EU, where a compassionate use programme has been set up, the applicant must ensure that patients taking part also have access to the new medicine between authorisation and placing on the market (European Medicines Agency, 2007; Regulation (EC) No 726/2004). National rules add their own duties. In Germany, the notification must state the criteria for suspending or ending the programme, and a programme ends with its termination, with the medicine's actual availability on the market, or at the latest one year after the confirmed notification, although it may then be notified again (Arzneimittel-Härtefall-Verordnung, 2010). In Italy, a company must tell AIFA the expected period of free supply and give at least 30 days' notice before closing a programme (Decreto 7 settembre 2017). In the US, the sponsor maintains an active IND until treatment has concluded and safety monitoring is complete (U.S. Food and Drug Administration, 2026b). Best practice includes providing a defined wind-down period, facilitating transition to commercial product where possible, and communicating clearly with patients and physicians about timelines and alternatives.

For the design work that comes before a programme opens, see our guide to planning an expanded access programme.

Frequently asked questions about compassionate use programmes for sponsors

Can a sponsor charge for a compassionate use medicine?

In the US the FDA lets sponsors recover direct costs under expanded access, not make a profit; in the EU the charging rules are national (21 C.F.R. § 312.8, 2026; Rosenberg et al., 2025).

Who reports adverse events in a compassionate use programme?

The sponsor collects, evaluates and reports adverse events, with the same discipline as in a clinical trial (21 C.F.R. § 312.32, 2026; 21 C.F.R. § 312.305, 2026).

What happens to patients when a compassionate use programme ends?

The sponsor plans continuity of care in advance: a defined transition, supply until authorised supply is available, or a clear and communicated exit (Regulation (EC) No 726/2004).

Can a sponsor outsource a compassionate use programme?

The sponsor keeps its regulatory responsibilities, but the operational work can be run by a partner: the national filings, the import and supply route, physician request handling and safety reporting in each market. Ideogen does this for partners across Europe, MENA, CIS and 94 markets worldwide, in orphan and rare disease. Write to [email protected].

What is the path forward for responsible sponsors?

Compassionate use programmes sit at the intersection of science, regulation and human urgency. Sponsors who approach these programmes with clear governance structures, transparent patient selection, rigorous pharmacovigilance and honest communication will not only meet their legal obligations but also build the kind of trust that sustains long-term relationships with regulators, physicians and the patients who depend on them. Requests are already rising: non-emergency individual patient expanded access INDs received by the FDA's drug centre grew from 880 in fiscal year 2021 to 1,326 in 2023 (U.S. Food and Drug Administration, 2024a), and the sponsors who have invested in scalable, ethical frameworks will be best positioned to respond. Every programme is, at its core, a promise to a patient: that access will be fair, that safety will be monitored, and that the obligation to care does not end when the trial does.

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