The Clinical Trials Regulation repealed the Clinical Trials Directive on 31 January 2023.
Although the Regulation entered into force on 16 June 2014 the timing of its application depended on the development of a fully functional EU clinical trials portal and database.
EMA Management Board confirmed to the European Commission on 21 April 2021 that the EU Portal and Database were fully functional. The publication of the subsequent Commission notice on 31 July 2021 fixed the date of applicability of the Clinical Trials Regulation on 31 January 2022. The notice can be consulted here.
The Regulation ensures a greater level of harmonisation of the rules for conducting clinical trials throughout the EU. It introduces an authorisation procedure based on a single submission via a single EU portal, an assessment procedure leading to a single decision, rules on the protection of subjects and informed consent, and transparency requirements.
It will also make it easier for pharmaceutical companies and non-commercial sponsors to conduct multinational clinical trials, which should increase the number of studies conducted within the EU.
EU Clinical Trial Portal and Database
Articles 80 and 81 of the Regulation assigned the EMA the task of creating an EU Portal and Database.
The portal, named Clinical Trials Information System (CTIS), was launched on 31 January 2022, starting the clock for one-year transition period for all sponsors of clinical trials.
During the transition period, clinical trial sponsors could choose whether to submit an initial clinical trial application in line with the Clinical Trials Directive or under the Clinical Trials Regulation (CTR), via CTIS.
On 31 January 2023, the CTIS became the single entry point for submission of data and information relating to clinical trials required by the Regulation. The EU Database will contain all data and information submitted via the EU Portal.
The CTIS is the backbone of the new regime for clinical trials in Europe. It considerably facilitates the application for clinical trials authorisation, in particular in case of multinational clinical trials, to the sponsor; the assessment carried out by national authorities; and access to clinical trials information by the general public.
For further information please consult the EMA website.
The Clinical Trials Regulation provides more transparency on clinical trials data. All information in the EU database will be publically accessible in CTIS unless its confidentiality can be justified on the basis of:
- Protection of commercially confidential information
- Protection of personal data
- Protection of confidential communication between EU countries
- Ensuring effective supervision of the conduct of clinical trials by EU countries
To support the transparency requirements of the Regulation, EMA has added two sets of requirements to the functional specifications for applying the exceptions:
- Features to support making information public
- Disclosure rules describing the practical implementation of the transparency rules.
The EMA Management Board endorsed both documents in 2015:
- Revision of section 6 of the "Functional specifications for the EU portal and EU database to be audited" setting out features to support making information public
- Appendix, on disclosure rules, to the "Functional specifications for the EU portal and EU database to be audited"
The Regulation simplifies the rules on safety reporting:
- The protocol may provide that not all adverse events (AE) and serious adverse events are recorded and reported.
- For a clinical trial involving more than one investigational medicinal product (IMP), a single annual safety report on all IMPs used in that trial can be submitted in the Clinical Trials Information System (CTIS).
- Suspected unexpected serious adverse reactions (SUSARs) need to be reported via the EudraVigilance database.
Commission legal obligations in the context of Regulation (EU) No 536/2014
The inspection of clinical trials may concern good clinical practice as regards the conduct of clinical trials as well as good manufacturing practices as regards the manufacturing of the investigational medicinal products.
For clinical trials submitted under the legal regime of the Regulation, 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 applies.
The Commision may conduct Union controls to verify whether Member States correctly supervise compliance with this Regulation. These controls shall be prepared in cooperation with Member States. Reports on these controls are available on CTIS. Union controls also can verify third country regumlatory system to ensure equivalence of the principles set in the Regualtion as regard safety of patient and robustness of generated data.
Clinical trials conducted outside the EU
If clinical trials are conducted outside the EU but submitted for marketing authorisation in the EU, they have to follow similar principles to the provisions of the Regulation as regards the rights and safety of the subject and the reliability and robustness of the data generated in the clinical trial.
This data should only be submitted in an application if the clinical trial has been registered ahead of time in a public register which is a primary or partner registry of, or a data provider to, the WHO ICTRP. The same applies to data gathered from a clinical trial that took place before the date of application of the regulation, or if the results have been published in an independent peer- reviewed scientific publication.