Compassionate Use (also: expanded access) refers to the controlled supply of a not-yet-authorised medicinal product to patients with a severe or life-threatening disease for which no satisfactory authorised therapy is available. The primary aim is not research, but to provide a therapeutic option under clearly defined conditions, while benefit-risk, quality and traceability are safeguarded.
In practice, compassionate use is often a bridging scenario: an active substance shows promising effects in early or ongoing late-stage development, but regular authorisation is not yet in place. In such situations, pressure arises from care needs, medical ethics and patient expectations. This is precisely why programmes must be designed so that they are medically justifiable and are documented in a regulatorily sound manner.
Distinction from clinical trials and off-label use
Compassionate use must be distinguished from a clinical trial: in a trial, scientific questions, the study protocol, randomisation and systematic data collection are at the forefront. In compassionate use, the focus is on treatment outside a trial. Nevertheless, safety information can (and should) be captured and reported in a structured way.
Compassionate use differs from off-label use in that off-label use involves an already authorised medicinal product used outside the terms of its authorisation, whereas compassionate use concerns a product that is not yet authorised. For project teams, the correct classification is important, because responsibilities, documentation obligations and liability issues vary considerably.
Regulatory framework in the EU and Germany
In the European Union, compassionate use is shaped, among other things, by Article 83 of Regulation (EC) No 726/2004, which enables Member States to establish programmes for groups of patients where an application for marketing authorisation has already been filed or clinical trials are ongoing. Implementation takes place at national level. In Germany, BfArM (or PEI for biologicals) is frequently involved; depending on the constellation, notification and approval pathways, medical responsibilities, and requirements for quality and pharmacovigilance may be relevant.
In practice, this means: the sponsor or manufacturer, treating physicians, and where applicable authorities coordinate on indication, inclusion and exclusion criteria, dosing, monitoring and documentation. The focus is on patient safety, a traceable supply chain, and appropriate informed consent. Programmes are often terminated or converted once a regular authorisation is granted or trials provide sufficient access.
Typical process and key documents
A robust compassionate use process includes: medical justification (unmet medical need), criteria for patient selection, physician-led risk disclosure, manufacturing and quality information about the product, and defined logistics including temperature control, traceability and inventory management. Even without a clinical study protocol, clear work instructions are advisable, for example in the form of a Standard Operating Procedure and a programme description document.
- Patient eligibility: documented indication, absence of alternatives, benefit-risk assessment.
- Informed consent: information on experimental status, known risks, alternatives and withdrawal.
- Medicinal product logistics: shipping, storage, accountability, return/destruction.
- Treatment documentation: dosing, concomitant medication, laboratory values, clinical observations.
From the sponsor’s and CRO’s perspective, it is particularly relevant that processes do not run “on the side”: training for treating physicians, clear contact channels for safety reporting, and clean batch documentation are prerequisites for responding consistently during audits or inspections. Especially in multicentre settings, harmonised templates (e.g. physician request, confirmation, treatment report) are a decisive success factor.
Pharmacovigilance and practical pitfalls
Even outside trials, pharmacovigilance remains central. Suspected cases of adverse drug reactions, in particular serious or unexpected events, must be reported to the manufacturer and, where applicable, to authorities in a timely manner. For manufacturers, it is essential to maintain a functioning safety organisation, including case intake, medical assessment, coding (e.g. MedDRA) and reporting into the relevant systems.
Operationally, programmes frequently fail on details: unclear responsibilities (medical vs. manufacturer), inconsistent documentation, insufficient training, or logistics without adequate traceability. Communication with patients must also be handled sensitively to avoid unrealistic expectations. Also relevant: data protection and consent for any form of data disclosure beyond routine care, particularly if analyses are intended for later marketing authorisation dossiers.
In practice, compassionate use is often used in parallel with late-stage clinical development or shortly before a conditional marketing authorisation. This increases the importance of a clean separation between therapy and research: data can provide indications but must not be misunderstood as a substitute for controlled evidence. Sound quality management helps to keep this boundary traceable.
Regulatory references (selection)
- Regulation (EC) No 726/2004, Art. 83 (compassionate use).
- ICH E2A/E2D (fundamentals of safety reporting) and ICH E6(R3) (Good Clinical Practice as a quality framework, where applicable).
- National requirements/guidance from BfArM or the Paul-Ehrlich-Institut (depending on the product class).
FAQ
When is a compassionate use programme sensible?
When patients urgently need a treatment option, no suitable authorised alternative exists, and the benefit-risk balance appears justifiable based on available data. An advanced stage of clinical development is often already in place.
Does compassionate use require ethics committee approval?
This depends on the national arrangement and the specific setting. Since it is not a clinical trial, ethics committee approval is not automatically required but may be sensible or required in individual cases, for example when accompanying data collection beyond routine care is planned.
What data may be collected under compassionate use?
It is permissible and advisable to capture safety-relevant information and essential treatment data for traceability. Systematic efficacy endpoints as in trials are possible but must be properly justified, compliant with data protection requirements, and implemented without constituting a “covert trial”.