Since its implementation on January 31, 2022, European Regulation 536/2014 has significantly reshaped the clinical research landscape across Europe. Its goal is clear: to make the European Union more attractive for clinical trials while ensuring maximum protection for participants.
Here is a closer look at the main principles and procedures introduced by this regulation.
European regulation 536/2014, a harmonized framework for the entire European Union
European regulation 536/2014 replaced Directive 2001/20/EC and established a unified framework for all clinical trials of medicinal products conducted in the 27 EU member states, as well as in Norway, Iceland, and Liechtenstein. It does not apply to non-interventional studies.
The regulation aims to simplify administrative procedures, harmonize authorization processes across countries, and speed up timelines, all while maintaining high standards for scientific validity and research ethics.
It should be noted that this regulation provides for the encouragement of clinical trials for the development of orphan medicinal products and medicinal products aimed at patients suffering from serious, debilitating and often life-threatening diseases that affect no more than one in 50,000 people in the European Union (ultra-rare diseases).
CTIS: the central portal for clinical transparency
At the core of the new system is the Clinical Trial Information System (CTIS), a centralized digital platform that all sponsors—academic or commercial—must use to submit their trial applications. This single-entry portal ensures greater transparency, provides public access to trial data, and strengthens monitoring throughout the entire trial lifecycle.
A two-part authorization process: part I and part II
Every clinical trial application is now assessed through two separate components:
- part I, which is evaluated by all participating member states and focuses on scientific and technical elements of the trial
- part II, which is assessed at the national level and addresses ethical and practical concerns
Part I includes information on the trial protocol, investigational products, and risk-benefit assessment. Part II covers country-specific issues such as participant recruitment, informed consent procedures, insurance coverage, and compliance with GDPR.
In France: coordinated review by ANSM and CPP
In France, the evaluation of part I is managed by the ANSM (National Agency for the Safety of Medicines and Health Products), while the part II decision is made by the CPPs (Committees for the Protection of Persons). The national authorization is called “single” because both parts must receive favorable opinions for the trial to proceed.
A strict 60-day timeline for authorization
One of the key innovations of the regulation is the introduction of fixed review timelines. National authorities must evaluate the application within 60 days. If no decision is issued within this period, the trial is automatically considered authorized. This system promotes efficiency while providing legal certainty to sponsors.
Two categories of clinical trials
The regulation defines two types of clinical trials:
- those involving high intervention
- those involving low intervention
Low-intervention trials involve approved medicines used in accordance with established practices and pose minimal risk to participants. This distinction allows regulatory demands to be adapted to the level of risk involved in each study.
Ethics at the heart of the regulation
Ethical safeguards are central to european regulation 536/2014. Approval of a trial depends not only on scientific merit but also on the protection of participants. Key requirements include:
- mandatory ethical review by an independent committee
- clear and informed consent processes
- additional protection for vulnerable groups, including minors, pregnant women, and emergency patients
Ongoing monitoring and data transparency
The regulation strengthens clinical trial oversight through:
- inspections by member states
- collaborative safety data assessments across the EU
- public access to trial results via CTIS, including for discontinued or inconclusive studies
references
- Regulation (EU) No. 536/2014 of the European Parliament and of the Council, April 16, 2014
- French Public Health Code – Article L.1124-1
- ANSM – National Agency for the Safety of Medicines
- EMA – European Medicines Agency
- CTIS – Clinical Trial Information System
