Planning Expanded Access Programmes for Biotech Sponsors

An expanded access programme lets seriously ill patients who cannot join a trial receive an investigational medicine, under 21 CFR Part 312, Subpart I in the US and Article 83 of Regulation (EC) No 726/2004 plus national rules in the EU. For a biotech sponsor, planning starts in Phase 2: define eligibility, check that supply can serve both trials and the programme, write the protocol, set up request review and safety reporting, and decide how the programme ends.

Expanded access programmes confront biotech sponsors developing investigational therapies with a critical decision long before regulatory approval: whether and how to provide their drug to seriously ill patients outside of clinical trials. They represent both a humanitarian obligation and a strategic undertaking, requiring careful planning across regulatory, operational, ethical and commercial dimensions. For small and mid-size biotech companies with limited resources, the stakes are particularly high, as a poorly structured programme can strain drug supply, complicate ongoing trials and create reputational risk; smaller companies are also less likely to have the public expanded access policy that US law requires (Kang et al., 2021). A well-designed programme, by contrast, can generate real-world safety information, show clinicians and patient communities that requests are handled fairly, and prepare the sponsor's teams for obligations that continue after a marketing authorisation. The question is not simply whether to offer pre-approval access but how to plan for it in a way that serves patients without undermining the broader development programme. This article addresses the essential considerations that biotech sponsors must weigh as they design, implement and sustain expanded access efforts in 2026 and beyond.

Why do the foundations of expanded access matter before planning?

Understanding the regulatory and conceptual underpinnings of expanded access is essential before any operational planning begins. These programmes exist at the intersection of patient need, regulatory policy and drug development strategy, and sponsors must grasp their formal structure before committing resources.

What is an expanded access programme?

An EAP, or expanded access programme, is a regulatory pathway that allows patients with serious or life-threatening conditions to receive investigational drugs outside of clinical trials when no comparable or satisfactory alternative therapy exists. The FDA codifies this pathway under 21 CFR Part 312, Subpart I (21 C.F.R. pt. 312, subpt. I, 2026; U.S. Food and Drug Administration, 2026a), while the EMA provides a parallel framework through Article 83 of Regulation (EC) No 726/2004 (European Medicines Agency, 2007; Regulation (EC) No 726/2004). These programmes can take several forms: individual patient access (sometimes called single-patient INDs), intermediate-size programmes for smaller patient populations, and treatment protocols designed for broader use (21 C.F.R. pt. 312, subpt. I, 2026). Each form carries distinct regulatory requirements regarding documentation, informed consent and reporting obligations. Terminology is not uniform. Article 83 covers programmes for groups of patients, while supply to a single named patient falls under Article 5 of Directive 2001/83/EC and national law (Directive 2001/83/EC; European Medicines Agency, 2007), and a review of US, European and Italian rules found programmes misclassified, for example registered as Phase 2, 3 or 4 trials, because the definitions differ (Iudicello et al., 2016). Sponsors should recognise that an EAP is not a substitute for clinical development but rather a parallel mechanism that demands its own governance structure, clinical oversight and resource allocation.

Building that infrastructure in-house is a real cost, and for a company running its first programme it rarely pays back. Ideogen provides it: the national filings, the request intake and review workflow, the import and supply route, and the safety reporting, across Europe, MENA, CIS and 94 markets worldwide. Talk to our experts about bridging access to unmet need in orphan and rare disease, where earlier access changes patient outcomes, at [email protected].

How does expanded access differ from a clinical trial?

Clinical trials generate controlled evidence under a protocol with predefined endpoints; expanded access puts the individual patient's benefit first and collects safety data rather than efficacy evidence.

The distinction between expanded access, often called compassionate use, and formal clinical trials is more than semantic; it shapes how sponsors allocate resources, collect data and manage risk. Clinical trials operate under tightly controlled protocols with predefined endpoints, randomisation and statistical power calculations. Expanded access, by contrast, prioritises individual patient benefit over data generation. There is no control group, no blinding and typically no primary efficacy endpoint, and the FDA itself notes that expanded access treatment generally occurs outside a controlled clinical trial setting (U.S. Food and Drug Administration, 2026b). Safety reporting remains mandatory (21 C.F.R. § 312.305, 2026), but the evidentiary standards differ significantly. Sponsors must also understand that expanded access does not generate the controlled data that regulatory agencies normally rely on for approval decisions, and the CHMP states plainly that compassionate use is not a substitute for properly conducted trials (European Medicines Agency, 2007). Safety signals identified through these programmes can, however, influence labelling and the assessment of a drug's risks: 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 they contributed to approved labelling (U.S. Food and Drug Administration, 2026b), and a review of FDA decisions from 2010 to 2016 found one instance in which safety events under expanded access alone led to potentially adverse labelling (Jarow & Moscicki, 2017). This distinction matters because it prevents sponsors from conflating the two pathways and inadvertently compromising either one.

How these routes compare in practice is set out in our article on expanded access versus compassionate use.

When should a sponsor start planning?

Strategic foresight separates sponsors who manage expanded access effectively from those who find themselves overwhelmed by ad hoc requests.

Planning should begin early in Phase 2, not as an afterthought during late-stage development.

US law fixes a point on that timetable. A manufacturer of an investigational drug for a serious disease must make its expanded access policy public by the first initiation of a Phase 2 or Phase 3 study, or 15 days after a breakthrough therapy, fast track or regenerative advanced therapy designation if that comes earlier (21 U.S.C. § 360bbb-0, 2024; U.S. Food and Drug Administration, 2026b). The risk to development also matters most at this stage: the FDA notes that the potential for expanded access to interfere with drug development is highest early in development and in rare diseases, and that for rare disease programmes well-controlled trials should generally start before patients are treated under expanded access (U.S. Food and Drug Administration, 2026b).

How do you set eligibility criteria?

Eligibility criteria for expanded access drugs must balance inclusivity with patient safety and programme sustainability. The regulatory floor is similar on both sides of the Atlantic: a serious or immediately life-threatening condition, no comparable or satisfactory alternative therapy, and a potential benefit that justifies the potential risks, in the FDA's terms (21 C.F.R. § 312.305, 2026), or a chronically or seriously debilitating or life-threatening disease that cannot be treated satisfactorily with an authorised medicine, in the EU's (Regulation (EC) No 726/2004). Sponsors should define clear clinical parameters on top of that floor: disease severity, prior treatment history, proximity to clinical trial sites, and contraindications that might elevate risk. Trial access is a criterion in its own right, since the FDA expects patients to be ineligible for, or otherwise unable to enter, ongoing trials, for example because they cannot reach a study site (U.S. Food and Drug Administration, 2026b). Overly broad criteria can flood the programme with requests that exceed supply capacity, while overly narrow criteria may invite criticism for restricting access to patients in genuine need. A tiered approach often works well, with the most urgent cases (those facing imminent mortality with no alternatives) receiving priority. Sponsors should also establish whether expanded access will be offered only in geographies where the drug is under active regulatory review or extended more broadly. Documenting these criteria transparently helps defend against allegations of arbitrary gatekeeping and provides a defensible framework for the independent review committees that evaluate individual requests. Some laws require it: in Germany, the notification of a programme must state the criteria for selecting patients and the expected number of patients (Arzneimittel-Härtefall-Verordnung, 2010).

Is your supply ready for a programme?

Drug supply is often the binding constraint on expanded access for investigational drugs, particularly for biologics, cell therapies and other complex modalities with long manufacturing lead times; one published allocation framework was built for a scarce investigational agent (Caplan et al., 2018). Sponsors must conduct a rigorous assessment of current and projected manufacturing capacity, factoring in the quantities needed for ongoing and planned clinical trials, regulatory submission batches and commercial launch inventory. Diverting supply to an expanded access programme without adequate planning can delay pivotal trials or leave the sponsor unable to meet commercial demand at approval, and in the US the FDA must be satisfied that expanded access will not interfere with the trials that could support approval (21 C.F.R. § 312.305, 2026). A practical approach involves earmarking a defined percentage of each manufacturing run for expanded access use, with clear escalation procedures if demand exceeds projections. Cold chain logistics, shelf life considerations and import and export requirements for international programmes add further complexity; in Italy, for instance, a medicine imported for compassionate use enters the country on presentation of the ethics committee's favourable opinion (Decreto 7 settembre 2017). Manufacturing rules apply in full: in Germany, the medicine in a programme must be manufactured, imported and released under the rules for investigational medicinal products (Arzneimittel-Härtefall-Verordnung, 2010). Early engagement with contract manufacturing organisations is advisable to ensure that expanded access demand does not create production bottlenecks.

Why is the expanded access protocol the core regulatory document?

Regulatory compliance is non-negotiable, and the expanded access protocol serves as the foundational document that governs the programme from a regulatory standpoint.

What goes into an expanded access protocol?

The expanded access protocol must satisfy regulatory requirements while remaining practical enough for treating physicians to follow in real-world clinical settings. Key components include a clear rationale for providing the drug outside of trials, a description of the patient population, dosing and administration guidelines, informed consent procedures and a detailed safety monitoring plan. In the US, the submission must include the rationale for the intended use, the criteria for patient selection, the method of administration, dose and duration of therapy, a description of the manufacturing facility, chemistry, manufacturing and controls information, pharmacology and toxicology information, and the clinical procedures and monitoring needed to evaluate the drug's effects and minimise its risks (21 C.F.R. § 312.305, 2026). The protocol should specify which adverse events require expedited reporting versus periodic aggregate reporting (21 C.F.R. § 312.32, 2026). For FDA submissions, sponsors file the protocol as a new IND or as a protocol amendment to an existing IND, and the FDA generally encourages a protocol under the existing IND when the sponsor already has one (21 C.F.R. § 312.305, 2026; U.S. Food and Drug Administration, 2026b). In the EU there is no EU-level submission by the company: programmes follow national procedures, and the EMA asks manufacturers not to request an opinion themselves, although a Member State may notify the Agency and the CHMP may then adopt one (European Medicines Agency, 2020; Regulation (EC) No 726/2004). In Germany, for example, the responsible person notifies BfArM or the Paul-Ehrlich-Institut through the Common European Submission Portal, and the programme may start only once the notification is confirmed (Paul-Ehrlich-Institut, n.d.; Arzneimittel-Härtefall-Verordnung, 2010). One common mistake is drafting the expanded access protocol as if it were a clinical trial protocol, loading it with unnecessary assessments and visit schedules that burden treating physicians and discourage participation. The FDA itself distinguishes expanded access protocols, whose primary intent is treatment, from continuation and open-label safety protocols, whose primary purpose is to obtain safety data (U.S. Food and Drug Administration, 2026b). The protocol should be lean, focused on safety, and designed for the clinical realities of treating seriously ill patients in diverse healthcare settings.

How do FDA and EMA requirements differ?

FDA and EMA requirements for expanded access share common principles but differ in procedural specifics. The FDA requires sponsors to submit an IND application or protocol amendment (21 C.F.R. § 312.305, 2026), and each treating physician must obtain IRB review and informed consent before treatment begins (21 C.F.R. § 312.305, 2026; U.S. Food and Drug Administration, 2025a). Streamlined routes exist. In an emergency, treatment can begin before IRB review, provided the use is reported to the IRB within 5 working days (21 C.F.R. § 56.104, 2026); for a non-emergency individual patient IND, the FDA intends to allow review by the IRB chair or a designated member instead of a convened board, on request (U.S. Food and Drug Administration, 2026b); and for a sponsor's multi-site protocol, a single IRB of record may review the protocol and the participating physicians (U.S. Food and Drug Administration, 2026b). The EMA framework relies on Member State implementation, meaning that sponsors must contend with varying national requirements across Europe, including differences in ethics committee review timelines, pharmacovigilance reporting formats and cost-recovery policies (European Medicines Agency, 2020; Rosenberg et al., 2025). The Clinical Trials Regulation (Regulation (EU) No 536/2014) has applied since 31 January 2022 (Commission Decision (EU) 2021/1240; Regulation (EU) No 536/2014), and Member States continue to update their compassionate use frameworks: France, for example, harmonised its early access and compassionate access procedures by Décret n° 2026-448, in force since 1 September 2026 (Décret n° 2026-448). Sponsors operating globally should map out regulatory requirements jurisdiction by jurisdiction and consider engaging local regulatory consultants in markets where they lack in-house expertise. Failure to comply with reporting obligations in any single jurisdiction can have cascading consequences for the broader development programme. The table sets the two systems side by side.

What does it take to run an expanded access programme day to day?

Translating a regulatory-compliant protocol into a functioning programme requires operational infrastructure that most early-stage biotech companies do not have in place by default.

How should physician requests be reviewed?

Through a structured intake process, such as a physician request portal, and an independent review committee, for example of clinicians, ethicists and regulatory specialists, that assesses each request against the programme's eligibility criteria.

A structured intake process is critical for managing the volume and complexity of expanded access requests. A web-based physician request portal can standardise the submission of patient clinical information, allow treating physicians to upload relevant medical records and track the status of each request through a defined review workflow. In the US, the law shapes the intake design: a manufacturer's public expanded access policy must give contact information, the procedures for making requests, the general criteria for evaluating them and the time the manufacturer expects to need to acknowledge receipt (21 U.S.C. § 360bbb-0, 2024). Companies may post the policy on their own website or on the Reagan-Udall Foundation's Expanded Access Navigator, and physicians can prepare and submit individual patient requests to the FDA with the foundation's eRequest app (U.S. Food and Drug Administration, 2024, 2026b). Behind the portal sits an independent review committee that evaluates each request against the programme's eligibility criteria; one published pilot used medical experts, bioethicists and patient representatives (Caplan et al., 2018). This committee structure serves two purposes: it ensures consistent decision-making across requests, and it insulates the sponsor from accusations of bias or commercial motivation in access decisions. Sponsors should establish service-level agreements for review turnaround times, recognising that patients seeking expanded access are often in urgent clinical situations where delays of even a few days can have meaningful consequences. Publishing a policy does not guarantee any individual patient access to a drug (21 U.S.C. § 360bbb-0, 2024).

What safety data must a programme collect?

Safety data from expanded access programmes, while not collected under the controlled conditions of a clinical trial, can provide valuable real-world evidence about a drug's safety profile in populations that may differ from trial participants (U.S. Food and Drug Administration, 2026b). Sponsors must implement systems for capturing adverse events, serious adverse events and any unexpected safety signals. In the US, that means IND safety reports within 15 calendar days, or 7 for unexpected fatal or life-threatening suspected adverse reactions, annual reports for uses that last a year or longer, and a written summary of results, including adverse effects, at the end of individual patient treatment (21 C.F.R. § 312.32, 2026; 21 C.F.R. § 312.310, 2026; 21 C.F.R. § 312.305, 2026). In Germany, the responsible person reports each suspected serious adverse reaction within 15 days and submits a final safety report covering all serious and all non-serious unexpected reactions (Arzneimittel-Härtefall-Verordnung, 2010). Electronic data capture platforms used for clinical trials can often be adapted for this purpose, though the data fields and visit schedules will be simpler. Periodic safety reports should be compiled and reviewed internally, with expedited reporting to regulatory authorities as required. One challenge specific to non-trial settings is ensuring that treating physicians, who may have limited experience with pharmacovigilance reporting, understand their obligations and have straightforward mechanisms for submitting safety data; in the US, investigators are responsible for reporting adverse drug events to the sponsor (21 C.F.R. § 312.305, 2026). Training materials and dedicated medical information support lines can help bridge this gap. Sponsors should also expect regulators to read these data in context: the FDA notes that expanded access patients may have more advanced disease, other therapies and comorbidities, which can make it difficult to attribute an event to the drug (U.S. Food and Drug Administration, 2026b). FDA review can also add safeguards: in a sample of 150 single-patient non-emergency INDs, the FDA recommended changes to dosing, safety monitoring or informed consent in 11 per cent (Jarow et al., 2017).

What ethical questions does expanded access raise?

The ethical dimensions of expanded access extend well beyond regulatory compliance, touching on fundamental questions of fairness, transparency and the responsible management of patient expectations.

How can sponsors ensure equitable access and transparency?

Equitable access is one of the most scrutinised aspects of any expanded access programme. Sponsors must demonstrate that their eligibility criteria and review processes do not systematically disadvantage patients based on geography, socioeconomic status, race or insurance coverage. Public disclosure of programme policies, including the criteria used to evaluate requests and aggregate data on the number of requests received, approved and denied, helps build trust with patient advocacy groups and regulatory bodies. In the US, part of that disclosure is a legal duty, since the expanded access policy must be public (21 U.S.C. § 360bbb-0, 2024), and practice still lags: an analysis of US companies with an oncology drug found a public policy at only 32 per cent of applicable companies, and all the information the law describes in 31 per cent of those policies (Kang et al., 2021). Where expanded access is available for a drug studied in an applicable clinical trial, the trial's ClinicalTrials.gov registration must also include an expanded access record (U.S. Food and Drug Administration, 2026b; 42 C.F.R. § 11.28, 2026). Cost recovery policies also warrant careful consideration: while FDA regulations permit sponsors to charge for expanded access drugs under certain conditions (21 C.F.R. § 312.8, 2026), doing so can create access barriers for uninsured or underinsured patients and generate negative public perception.

The duties that follow once a programme is running are set out in our article on sponsor obligations in compassionate use.

How should sponsors manage expectations for unapproved therapies?

Patients seeking expanded access are often in desperate clinical situations, and the informed consent process must clearly communicate that the investigational drug has not been proven safe or effective through the full regulatory review process. The FDA's own wording is direct: it has not found investigational products to be safe and effective for their specific use, the product may or may not be effective, and its use may cause unexpected serious side effects (U.S. Food and Drug Administration, 2026a). Its consent template for individual patient expanded access asks for a statement that the product is investigational and not approved as safe and effective, and that participation is voluntary and can be stopped at any time without penalty (U.S. Food and Drug Administration, 2026b). This is not merely a legal formality; it is an ethical obligation to ensure that patients and their families understand the uncertainties involved. Consent documents should describe known and potential risks, the absence of guaranteed benefit, and the possibility that treatment may be discontinued if supply becomes unavailable or if safety concerns emerge. Sponsors should also prepare treating physicians with communication guides that help frame these conversations with appropriate sensitivity. The goal is neither to discourage patients from seeking access nor to create unrealistic hope, but to ensure that the decision to pursue treatment is genuinely informed.

How does expanded access shape launch and market access?

Expanded access programmes do not exist in isolation from a sponsor's broader commercial strategy. The decisions made during pre-approval access can shape market dynamics, payer relationships and the sponsor's reputation for years after a product reaches the market. Continuity is the first link: in the EU, a sponsor that has set up a compassionate use programme must keep participating patients supplied between authorisation and placing on the market (Regulation (EC) No 726/2004); Italy requires the company to declare the presumed period of free supply and to give AIFA 30 days' notice of closure (Decreto 7 settembre 2017); and in France a company supplying a new medicine in development under compassionate access must commit to applying for early access within 12 months, or 18 months for a rare disease (Agence nationale de sécurité du médicament et des produits de santé, 2026). France's early access schemes, financed through social insurance, also cover the period after authorisation and before reimbursement (Tarantola et al., 2023). Real-world safety data collected through expanded access can inform post-marketing commitments and risk evaluation and mitigation strategies (REMS), the safety programmes the FDA can require for certain medicines with serious safety concerns (U.S. Food and Drug Administration, 2025b). Regulators have also used expanded access data at approval: a review of FDA and EMA approvals found 39 in which such data informed the assessment of efficacy (Polak et al., 2020), while a seven-country analysis found disparities in the availability and duration of compassionate use programmes before and after EU marketing authorisation (Rosenberg et al., 2025). Contact with treating physicians during a programme must stay non-promotional: a sponsor may not represent an investigational drug as safe or effective, or otherwise promote it (21 C.F.R. § 312.7, 2026), and in the EU a medicine without a marketing authorisation may not be advertised (Directive 2001/83/EC). Conversely, negative experiences, whether clinical, logistical or communicative, can damage a product's reputation before it ever reaches pharmacy shelves.

Frequently asked questions about planning expanded access programmes

When should a biotech sponsor start planning expanded access?

Early in Phase 2, before requests arrive, so eligibility, supply and review processes are in place (21 U.S.C. § 360bbb-0, 2024; U.S. Food and Drug Administration, 2026b).

What does an expanded access protocol contain?

The rationale for supply outside trials, the patient population, dosing and administration, informed consent, and a safety monitoring and reporting plan (21 C.F.R. § 312.305, 2026).

Does expanded access data count as evidence?

It adds real-world safety information on patients who may differ from trial participants, but it is collected outside controlled conditions and does not replace trial evidence (European Medicines Agency, 2007; U.S. Food and Drug Administration, 2026b).

What if a sponsor does not have the infrastructure to run an expanded access programme?

It can be run by a partner. The sponsor keeps its regulatory responsibilities and its decisions on eligibility and supply; the partner provides the national filings, the physician request intake and review workflow, the import and supply route, and the safety reporting in each market. Ideogen does this for biotech partners across Europe, MENA, CIS and 94 markets worldwide, in orphan and rare disease. Talk to our experts to bridge access to unmet needs in orphan and rare disease that change patient outcomes at [email protected].

What do sponsors need to plan for expanded access?

Biotech sponsors planning expanded access programmes should approach them as integrated components of their development and commercialisation strategy rather than isolated humanitarian gestures. Well-run programmes share common traits: early planning, clear governance, transparent communication and a genuine commitment to serving patients who have exhausted other options. For sponsors asking what they need to plan for expanded access, the answer spans regulatory preparation, supply chain readiness, operational infrastructure, ethical frameworks and long-term commercial awareness. Each of these dimensions requires dedicated resources and cross-functional coordination. The companies that invest in this planning early will find themselves better positioned not only to meet their obligations to patients but also to manage the move from programme supply to authorised supply with a stronger foundation of clinical experience and stakeholder trust.

Next step: our managed access programme partner services.

References

Agence nationale de sécurité du médicament et des produits de santé. (2026, May 29). Accès compassionnel [Compassionate access]. https://ansm.sante.fr/vos-demarches/industriel/acces-compassionnel

Arzneimittelgesetz in der Fassung der Bekanntmachung vom 12. Dezember 2005 (BGBl. I S. 3394), zuletzt geändert durch Artikel 2 Absatz 4 des Gesetzes vom 12. Mai 2026 (BGBl. 2026 I Nr. 143), § 21 Zulassungspflicht [Medicinal Products Act, section 21: Requirement for marketing authorisation]. (2005). Gesetze im Internet. https://www.gesetze-im-internet.de/amg_1976/__21.html

Caplan, A. L., Teagarden, J. R., Kearns, L., Bateman-House, A. S., Mitchell, E., Arawi, T., Upshur, R., Singh, I., Rozynska, J., Cwik, V., & Gardner, S. L. (2018). Fair, just and compassionate: A pilot for making allocation decisions for patients requesting experimental drugs outside of clinical trials. Journal of Medical Ethics, 44(11), 761-767. https://doi.org/10.1136/medethics-2016-103917

Charging for investigational drugs under an IND, 21 C.F.R. § 312.8 (2026). https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-312/subpart-A/section-312.8

Commission Decision (EU) 2021/1240 of 13 July 2021 on the compliance of the EU portal and the EU database for clinical trials of medicinal products for human use with the requirements referred to in Article 82(2) of Regulation (EU) No 536/2014 of the European Parliament and of the Council. (2021). Official Journal of the European Union, L 275, 1-2. https://eur-lex.europa.eu/eli/dec/2021/1240/oj

Decreto 7 settembre 2017 del Ministero della Salute. Disciplina dell'uso terapeutico di medicinale sottoposto a sperimentazione clinica [Decree of the Ministry of Health of 7 September 2017 governing the therapeutic use of medicinal products under clinical trial]. (2017). Gazzetta Ufficiale della Repubblica Italiana, Serie Generale n. 256 (2 November 2017). https://www.gazzettaufficiale.it/eli/id/2017/11/02/17A07305/sg

Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. (2001). Official Journal of the European Communities, L 311, 67-128. https://eur-lex.europa.eu/eli/dir/2001/83/oj

Décret n° 2026-448 du 3 juin 2026 harmonisant les dispositions applicables aux accès précoces et aux accès compassionnels [Decree No 2026-448 of 3 June 2026 harmonising the provisions on early access and compassionate access]. (2026). Journal officiel de la République française, n° 0130, texte n° 33 (5 June 2026). https://www.legifrance.gouv.fr/jorf/id/JORFTEXT000054200257

European Medicines Agency, Committee for Medicinal Products for Human Use. (2007). Guideline on compassionate use of medicinal products, pursuant to Article 83 of Regulation (EC) No 726/2004 (EMEA/27170/2006). https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/guideline-compassionate-use-medicinal-products-pursuant-article-83-regulation-ec-no-7262004_en.pdf

European Medicines Agency. (2020, October 26). Compassionate use. https://www.ema.europa.eu/en/human-regulatory-overview/research-development/compassionate-use

Exemptions from IRB requirement, 21 C.F.R. § 56.104 (2026). https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-56/subpart-A/section-56.104

Expanded access policy required for investigational drugs, 21 U.S.C. § 360bbb-0 (2024). https://www.govinfo.gov/content/pkg/USCODE-2024-title21/html/USCODE-2024-title21-chap9-subchapV-partE-sec360bbb-0.htm

Expanded Access to Investigational Drugs for Treatment Use, 21 C.F.R. pt. 312, subpt. I (2026). https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-312/subpart-I

IND safety reporting, 21 C.F.R. § 312.32 (2026). https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-312/subpart-B/section-312.32

Individual patients, including for emergency use, 21 C.F.R. § 312.310 (2026). https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-312/subpart-I/section-312.310

Iudicello, A., Alberghini, L., Benini, G., & Mosconi, P. (2016). Expanded access programme: Looking for a common definition. Trials, 17(1), Article 21. https://doi.org/10.1186/s13063-015-1108-0

Jarow, J. P., & Moscicki, R. (2017). Impact of expanded access on FDA regulatory action and product labeling. Therapeutic Innovation & Regulatory Science, 51(6), 787-789. https://doi.org/10.1177/2168479017707800

Jarow, J. P., Lemery, S., Bugin, K., & Lowy, N. (2017). Ten-year experience for the Center for Drug Evaluation and Research, part 2: FDA's role in ensuring patient safety. Therapeutic Innovation & Regulatory Science, 51(2), 246-249. https://doi.org/10.1177/2168479016679214

Kang, S., Chang, S., Ross, J. S., & Miller, J. E. (2021). Implementation of 21st Century Cures Act expanded access policies requirements. Clinical Pharmacology & Therapeutics, 110(6), 1579-1584. https://doi.org/10.1002/cpt.2401

Paul-Ehrlich-Institut. (n.d.). Compassionate use programmes. Retrieved October 4, 2026, from https://www.pei.de/EN/regulation/clinical-trials/compassionate-use/compassionate-use-node.html

Polak, T. B., van Rosmalen, J., & Uyl-de Groot, C. A. (2020). Expanded Access as a source of real-world data: An overview of FDA and EMA approvals. British Journal of Clinical Pharmacology, 86(9), 1819-1826. https://doi.org/10.1111/bcp.14284

Promotion of investigational drugs, 21 C.F.R. § 312.7 (2026). https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-312/subpart-A/section-312.7

Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency. (2004). Official Journal of the European Union, L 136, 1-33. https://eur-lex.europa.eu/eli/reg/2004/726/oj

Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC. (2014). Official Journal of the European Union, L 158, 1-76. https://eur-lex.europa.eu/eli/reg/2014/536/oj

Requirements for all expanded access uses, 21 C.F.R. § 312.305 (2026). https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-312/subpart-I/section-312.305

Rosenberg, N., Post, H. C., Schutte, T., de Visser, S. J., Bartelink, I., Pasmooij, A. M. G., van Laarhoven, H. W. M., & Hollak, C. E. M. (2025). Access to anticancer and orphan medicines through compassionate use programs and named patient basis in seven European countries. ESMO Open, 10(11), Article 105855. https://doi.org/10.1016/j.esmoop.2025.105855

Tarantola, A., Otto, M. H., Armeni, P., Costa, F., Malandrini, F., & Jommi, C. (2023). Early access programs for medicines: Comparative analysis among France, Italy, Spain, and UK and focus on the Italian case. Journal of Pharmaceutical Policy and Practice, 16(1), Article 67. https://doi.org/10.1186/s40545-023-00570-z

U.S. Food and Drug Administration. (2024, October 16). Expanded access: Information for industry. https://www.fda.gov/news-events/expanded-access/expanded-access-information-industry

U.S. Food and Drug Administration. (2025a, September 16). For physicians: How to request single patient expanded access (“compassionate use”). https://www.fda.gov/drugs/investigational-new-drug-application-ind/physicians-how-request-single-patient-expanded-access-compassionate-use

U.S. Food and Drug Administration. (2025b, May 20). Risk evaluation and mitigation strategies | REMS. https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems

U.S. Food and Drug Administration. (2026a, October 1). Expanded access. https://www.fda.gov/news-events/public-health-focus/expanded-access

U.S. Food and Drug Administration. (2026b, April). Expanded access to investigational drugs for treatment use: Questions and answers [Guidance for industry, Procedural, Revision 2]. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expanded-access-investigational-drugs-treatment-use-questions-and-answers

Verordnung über das Inverkehrbringen von Arzneimitteln ohne Genehmigung oder ohne Zulassung in Härtefällen (Arzneimittel-Härtefall-Verordnung, AMHV) vom 14. Juli 2010 (BGBl. I S. 935), zuletzt geändert durch Artikel 8 der Verordnung vom 6. Juli 2022 (BGBl. I S. 1102) [Ordinance on placing medicinal products on the market without approval or authorisation in cases of hardship]. (2010). Gesetze im Internet. https://www.gesetze-im-internet.de/amhv/BJNR093500010.html

What constitutes clinical trial registration information?, 42 C.F.R. § 11.28 (2026). https://www.ecfr.gov/current/title-42/chapter-I/subchapter-A/part-11/subpart-B/section-11.28