2. Early access
3. Compassionate use
3.5. Compassionate use versus clinical trials
Article 83 (9) of Regulation (EC) No 726/2004 states that Article 83 “shall be without prejudice to Directive 2001/20/EC” (Directive to be replaced by Regulation (EU) 536/2014 on January 22, 2022). From a methodological point of view, clinical trials are practically the only means of obtaining reliable and interpretable efficacy and safety data for a medicine. Although safety data and real-world data (in some programmes, e.g., in France) may be collected or are mandatory during CUPs, such programmes cannot replace or be a substitute for clinical trials for investigational purposes. Compassionate use should therefore not slow down the implementation or continuation of clinical trials intended to provide essential information pertaining to the benefit/risk balance of a medicine. Patients should always be considered for inclusion in clinical trials before being offered compassionate use programmes.
Article 83 (1) of Regulation (EC) No 726/2004 introduces the legal framework for the provision of compassionate use in the European Union for medicines that are eligible to be authorised via the Centralised Procedure, stating that “by way of exemption from Article 6 of Directive 2001/83/EC (“No medicinal product may be placed on the market of a Member State unless a marketing authorisation has been issued…”), MS may make a medicinal product for human use belonging to the categories referred to in Article 3(1) and 3(2) of Regulation (EC) No 726/2004 available for compassionate use”.
The term “compassionate use” should be used in line with the definition in Article 83 of Regulation (EC) 726/2004 as:
a) a medicine to be made available to “patients with a chronically or seriously debilitating disease, or a life-threatening disease, and who cannot be treated satisfactorily by an authorised medicinal product” in the European Union
b) the medicine is either “the subject of an application for a centralised marketing authorisation in accordance with Article 6 of Regulation (EC) No 726/2004 or is undergoing clinical trials” in the European Union or elsewhere
c) the compassionate use programme is intended for a “group of patients”. Thus, the term compassionate use is legally restricted only for cohort approaches. However, in some Member states (MS), the term is used for both, cohorts and individual access. The inclusion of cohorts of patients also implies that, in this case, granting access would most likely occur in the later phases of development when enough knowledge on the product is available. In some MS, early access programmes extend beyond when a marketing authorisation is granted but also to access once a decision on price & reimbursement has been made.
As a consequence, Article 83 is not applicable to:
- Medicines which are not eligible for the Centralised Procedures,
- Compassionate use on a named patient basis (Article 5 of Directive 2001/83/EC),
- A medicine, which has already been authorised via the Centralised Procedure, even if the proposed conditions of use and target population are different from those of the marketing authorisation.
However, the existence of a Community authorisation for a medicine does not affect any national legislation relating to compassionate use.