Clinical trials are scientifically controlled studies undertaken in humans to establish or confirm the safety and effectiveness of investigational medicinal products (IMPs). Clinical trials in the EU are governed by the Clinical Trials Regulation, which became effective on 31 January 2022.
The Clinical Trials Regulation (CTR) aims to ensure greater harmonisation of the rules of conducting clinical trials in the EU. It features:
- a streamlined application procedure for all clinical trials conducted in Europe in a single EU portal and database, the Clinical Trials Information System (CTIS), which is the single-entry point for sponsors and regulators of clinical trials to submit and assess clinical trial applications since 31 January 2023;
- a single authorisation procedure for all clinical trials for faster and better assessment by all EU countries concerned;
- the extension of the silent agreement principle to the authorisation process provides legal certainty to sponsors and researchers, particularly SMEs and academics; and
- greater transparency for clinical trial data.
Key guidance documents for the Clinical Trials Regulation
- Questions and Answers Document - Regulation (EU) 536/2014
- Annex II of the Q&A provides the language requirements for part I documents. Annex III of the Q&A provides lists of Member States websites specifying national requirements and contact details for Part I and Part II application
- Quick guide for sponsors - Regulation 536/2014 in practice
- Q&A on the interface between Regulation (EU) 536/2014 on clinical trials for medicinal products for human use (CTR) and Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR)
- Question and Answers on the interplay between the Clinical Trials Regulation and the General Data Protection Regulation
Guidelines on the conduct of clinical trials
The guidelines on the conduct of clinical trials can be found in Eudralex Volume 10. A number of relevant guidelines and recommendations have been revised and updated in line with the changes and requirements of the Clinical Trials Regulation. Guidances and recommendations are also available on specific subject s such as complex clinical trials and decentralised elements of clinical trials.
Transition from the Clinical Trials Directive to Regulation
Until the Clinical Trials Regulation EU No 536/2014 became applicable, all clinical trials performed in the European Union were required to be conducted in accordance with the Clinical Trials Directive (CTD). A transition phase of 3 years ensures that ongoing trials are progressively transferred to the rules of the Regulation, at the latest by 31 January 2025.
- From 31st January 2023 all new initial clinical trial applications should be submitted under the CTR using CTIS.
- From 31st January 2025 all ongoing clinical trials with an active site in the EU/EEA should be conducted under the CTR using CTIS. Only these trials have to be transitioned before 31 January 2025.
- For clinical trials authorised under the CTD and not transitioned to CTR, substantial amendments and other reporting obligations should take place according to CTD procedures until 31 January 2025.
- Guidance for the Transition of clinical trials from the Clinical Trials Directive to the Clinical Trials Regulation. This guidance supersedes Chapter 11 of Questions and Answers Document - Regulation (EU) 536/2014 version 6.4 and should be read in conjunction with the CTCG guidance for sponsors on transition of multinational trials.
- Additional guidance is also available on the Heads of Medicines Agencies: Clinical Trials Coordination Group website and the Module 23 of the CTIS online training programme:
Implementation and enforcement of the Clinical Trials Regulation
- The Clinical Trials Regulation sets the Clinical Trials Coordination and Advisory Group in order to support the exchange of information between the Member States and the Commission on the experience acquired with regard to its implementation. Rules of procedures, agendas and minutes of meetings are publicly available.
- The Commission and Member States meet regularly in the Expert Group on clinical trials to discuss the implementation of the Clinical Trials Regulation. Agendas and minutes from the meeting are published on the Commission Register of Expert Groups.
- The Heads of Medicines Agencies established the Clinical Trials Coordination Group (CTCG) (in which the Commission and EMA are observers), in order to discuss ongoing technical issues.
- During this 1st transition year, stakeholders gained some initial experience using the CTIS, the new rules and how these were implemented. In this view, an EU survey was launched from 18 July to 9 September 2022 to have feedback from sponsors and stakeholders on the new regulatory environment and the use of CTIS.
- A report summarises this feedback, offering solutions to the problems encountered.
Delegated acts and implementing acts other applicable legislation
The Commission's GCP Directive will apply to clinical trials submitted under the Clinical Trials Directive until 31/1/2025, except for the provisions in chapters 5 and 6 of this Directive which are related to inspectors and inspection procedures. These aspects are covered by the Implementing Regulation (EU) 2017/556 of 24 March 2017 on detailed arrangements for the good clinical practice inspection procedures pursuant to Regulation (EU) No 536/2014 of the European Parliament and of the Council, which became applicable at the same time as Regulation (EU) No 536/2014 and applies to all GCP inspections (this means, inspections of clinical trials conducted under the Regulation as well as the Directive).
The Commission Delegated Regulation (EU) 2017/1569 of 23 May 2017 supplementing Regulation (EU) No 536/2014 became applicable, as a matter of principle, to all clinical trials as 31/1/2022. It specifies principles and guidelines for good manufacturing practice for investigational medicinal products for human use, and arrangements for inspections.
During the transitory period (i.e. until 31/1/2025), EU countries may however continue to apply their national law, adopted in order to transpose Directive 2003/94/EC, to those clinical trials conducted under the Directive 2001/20/EC. Additionally, the detailed Commission guideline, adopted on 8 December 2017, on the good manufacturing practice for investigational medicinal products, pursuant to the second paragraph of the Article 63(1) of Regulation (EU) No 536/2014 became applicable on 31/1/2022 as well.
Commission Implementing Regulation (EU) 2022/20 of 7 January 2022, laying down rules for the application of Regulation (EU) No 536/2014 of the European Parliament and of the Council as regards setting up the rules and procedures for the cooperation of the Member States in safety assessment of clinical trials, became applicable on 31/1/2022.
Commission Delegated Regulation (EU) 2022/2239 of 6 September 2022 amending Regulation (EU) No 536/2014 of the European Parliament and of the Council as regards labelling requirements for unauthorised investigational and unauthorised auxiliary medicinal products for human use was adopted by the Commission on 6 September 2022.