EU Clinical Trial Regulation V2

Our expert regulatory affairs team go through everything you need to know about the EU Clinical Trials Regulation.

The European Clinical Trial Regulation, EU No. 536/2014 (CTR) has now come into effect. It brings about many changes to the clinical trial landscape with the aim of harmonizing the requirements for conducting clinical trials throughout the EU and EEA and focusing on increasing patient safety and transparency of clinical trial data. The CTR provides a single application route for clinical trials thereby making Europe a more competitive region for clinical trials.

Although the CTR is effective from 31 January 2022, there is a 3 year transition period applicable for clinical trials authorized under Directive 2001/20/EC to transition to the Regulation with the following timelines applying:

Eu Clinical Trial Regulation Timeline

Some of the key areas that will change within the clinical trial environment with the introduction of the CTR are discussed further below.


The CTR brings a big change in how clinical data can be viewed by the public as the CTR aims to increase transparency within the EU through the publicly accessible CTIS database. The change means that all information including the trial protocol, investigator’s brochure (IB), assessment and inspection reports will be publicly accessible unless one or more of the following exceptions apply:

  • for the protection of personal data;
  • for the protection of commercially confidential data;
  • for the protection of confidential communications between Member States (MSs) in the preparation of an assessment report;
  • for the protection of the supervision of clinical trials by MS.

Publication of the data will be made at the time of the decision on an application by the MS, unless a request for a deferral of the publication was made in CTIS during the application process.

Clinical Trial Information System (CTIS)

The introduction of the CTR brings in the introduction of the Clinical Trials Information System (CTIS) which acts as both the single entry-point for the submission of clinical trial data and as the clinical trial database.

CTIS has been developed to support the application of the CTR and provides an integrated system that covers the entire life cycle of a clinical trial incorporating the submission, review, and outcome of an application through the portal and also provides the public access to trial information. CTIS is composed of two workspaces with secured and restricted access; one for Sponsors and one for Authorities (Member States and the European Commission), and also a publicly accessible website.

All applications required during the life-cycle of a clinical trial including initial trial application, notifications, modifications, and study reports are prepared and submitted using CTIS. Additionally, CTIS allows users to modify data directly within the system and provides all communication between Sponsors and MSs regarding a trial.

CTIS requires users to be assigned to one of the CTIS user roles within the system to be able to perform certain tasks such as preparing, submitting, or viewing a clinical trial application. Each CTIS user role carries appropriate permissions, therefore the level of access will differ between the different users. Further information on the various roles within CTIS and the different aspects of CTIS can be found within the EMA’s module training program.

Dossier Requirements and Assessment Procedure

Under Directive 2001/20/EC, the application dossier and timelines for assessment varied considerably between MSs with timelines for assessment not always being followed in practice.

The CTR simplifies the assessment procedure through a coordinated review by both the Competent Authority and Ethics Committee leading to a single decision on a clinical trial application per MS and provides defined timelines for the assessment to be adhered to by all MSs involved.

Under the CTR, the application dossier will consist of two parts, a ‘scientific’ part (Part I) and a national part (Part II):

  • Part I consists of information related to the trial and product that are subject to common assessment and will be the same for each of the MSs involved. Part I of the application dossier includes the trial protocol, IB, investigational medicinal product dossier (IMPD) and labelling.
  • Part II consists of information specific to the MS where the trial will be conducted and will be assessed nationally by each national ethics committee. Part II of the application includes the subject information and informed consent documents, the suitability of the investigator and trial site, and information on data protection.

The initial application must always consist of Part I, however, Sponsors have the option of submitting Part II up to two years after the conclusion of Part I.

CTIS allows the sponsor to decide which MS to include in their application. A Reporting Member State (RMS) who will lead the assessment of Part I can be proposed if the trial is to be conducted in several countries.

Once the assessment of Part I has been made, the RMS will prepare an assessment report with its conclusions on the application via CTIS. Based on the outcome of the report in addition to the relevant Ethics Committee’s opinion on Part II, the MS involved in the application will provide a national decision on the trial which is required before a trial can commence in each MS.

How can S-cubed help you?

We can prepare and coordinate all the necessary regulatory documentation you may require for a clinical trial in the EU, including IMPDs and IBs, (ensuring these meet the requirements of the CTR). We can also support the submission through to determination, and throughout the life-cycle of a clinical trial.

Any Questions?

If you have any questions on this topic, please don’t hesitate to ask. You can contact us through our website, via email (, and telephone (S-cubed Ltd: +44 1235 77 22 60).