Clinical Trial Regulation (CTR)


From 31st January 2023, it will no longer be possible to submit new initial clinical trial applications under the Clinical Trials Directive.  It will also no longer be possible to add new Member States (MS) to existing trials approved under the Directive without first transitioning to the new Clinical Trial Regulation (CTR).  For trials authorised under the Directive, sponsors can continue to submit substantial amendments following the principles of the Clinical Trial Directive until the end of the transition period on 31st January 2025.

By 31st January 2025 all active EU clinical trials must have transitioned to the CTR (meaning that these trials will need to be approved under the CTR by this date to continue).


What are the key changes under the CTR:


  • Single application via CTIS to all MS – CTIS submissions are split into a Part I submission largely consisting of the core technical dossier (protocol, Investigator Brochure, IMPD etc.) which is assessed jointly by all MS involved and Part II dossier comprised of national documents which are assessed per MS.
  • Specific submission document requirements – CTIS submissions are based on pre-defined placeholders both for the Part I and Part II submissions in order to harmonise submissions across MSs.  Core documents must be either harmonised or consolidated, meaning that country specific protocols etc. are not accepted.  There are also updated requirements for specific documents e.g. label requirements are now prescribed under Annex IV of the CTR.  In addition, there are country specific translation requirements for all submission documents and CTIS submission fields which need to be considered.
  • Stricter transparency and disclosure rules – one of the main principles under CTR is the increased transparency of clinical trial information to the research community and the general public, as such all submission information (except for quality related material) will be made public via CTIS (  There are additional considerations associated with this concerning the redaction of commercially sensitive and personal data and publication deferral timeline requests depending on the nature of the study (phase/population etc.).
  • Increased reporting milestones – CTIS notifications are used to inform MSs of key milestones and events during the lifecycle of a trial, these include; trial and recruitment milestones and circumstantial notifications such as unexpected events, urgent safety measures, serious breaches and inspection reports.  Again some of this information is subject to publication requirements.
  • Standardised timelines – under CTR all MSs are subject to the same assessment timelines, these may be shorter or longer than national timelines under the Directive (in the main though slightly longer).  There are also strict timelines for Sponsors to respond to queries (called RFIs under the CTR), this is a maximum of 12 calendar days.  Sponsors must be prepared to work quickly to meet these tight time frames.
  • Restrictions on modification submissions – whereas under the Directive it is possible to overlap amendment submissions within and across MS, under the CTR it is not possible to submit modifications (the new terminology for amendments) during ongoing reviews (except for distinct Part II modification).  This has obvious implications for planning and strategizing submission approaches with respect to ongoing study maintenance.


Note that the trials transitioning to the CTR will need to satisfy and be subject to all of the above requirements.

All in all, theses are significant changes impacting both new and ongoing studies and there is a huge amount to consider.  Whether you are a fully informed Sponsor looking for support with CTIS submissions or just starting to understand the the basics and would like an initial overview, Fusion Pharma can help.


Fusion Pharma can provide client training covering the following areas:
  • Overview of CTR
  • CTIS/OMS Registration
  • CTIS User Access Management
  • CTR Data Transparency Rules
  • CTR Submission Requirements
  • CTR Submission Planning


If you would like to discuss how Fusion Pharma can support you with clinical trials please email us at or phone us on +44 (0) 203 1379 799.


While the information in this article is considered to be true and correct at the date of publication, changes in guidance and/or experience may impact on the accuracy of the information.  Please refer to the relevant guidance for the latest information.