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
Regulation (EU) No 536/2014 lays down rules on clinical trials on medicinal products for human use and repeals Directive 2001/20/EC. Adopted by the European Parliament and the Council and published in the Official Journal L 158 of 27 May 2014, it is directly applicable in all Member States and has relevance for the European Economic Area. For investigator‑initiated clinical studies on medicinal products, this Regulation is the central legal source defining sponsor and investigator obligations, ethical and scientific assessment processes, safety reporting, documentation standards and transparency requirements across Member States.
Its main objectives are to protect the rights, safety, dignity and well‑being of trial subjects and to ensure that data generated in clinical trials are reliable and robust. The Regulation clarifies the concepts of clinical study and clinical trial, distinguishes trials from non‑interventional studies, and requires prior authorisation for clinical trials.
It addresses previous barriers to multinational research by introducing a single application dossier submitted through a Union portal and Union database for all concerned Member States, implemented as the Clinical Trials Information System (CTIS). Member States cooperate in assessing the application within defined timelines, with coordinated evaluation and the possibility of tacit authorisation. A risk‑adapted framework is established through the category of low‑intervention clinical trials, where the additional risk compared with normal clinical practice is minimal and certain requirements, such as monitoring intensity and documentation, are simplified.
The Regulation sets detailed rules on ethics and informed consent, including language that is easily understood by participants, written consent or equivalent documentation, and specific safeguards for minors, incapacitated persons, pregnant or breastfeeding women and other vulnerable groups, as well as provisions for emergency situations.
Key operational provisions cover the content and assessment of the application dossier, substantial modifications, extension of trials to additional Member States, allocation of sponsor responsibilities, co‑sponsorship, liability and compensation systems, and the possibility for authorities to suspend, modify or revoke a trial.
Safety reporting requirements specify how investigators and sponsors must record and report serious adverse events and suspected unexpected serious adverse reactions, and how information is transmitted to the European Medicines Agency and Member States. The Regulation also contains rules on manufacturing, import and labelling of investigational and auxiliary medicinal products, referencing good manufacturing practice and allowing limited flexibilities, for example for some hospital‑prepared radiopharmaceuticals.
Transparency provisions require registration of all clinical trials, submission of result summaries (including a layperson summary) and establishment of a publicly accessible Union database, accessed via the Union portal, that contains key information and documents on authorised and conducted trials while protecting personal data and legitimate economic interests in clearly defined circumstances.