What is the Clinical Trial Information System (CTIS)?
With the introduction of EU Regulation 536/2014 (Clinical Trial Regulation), the Clinical Trial Information System (CTIS) was established as a new tool for clinical trials in the EU. This is an electronic portal for submitting, assessing, and supervising clinical trials, as well as a database for public searches of information regarding authorized clinical trials.
CTIS enables the centralized submission of clinical trials in up to 30 EU/EEA countries simultaneously through a single application. This includes submissions to both national competent authorities and ethics committees.
The background to this new system is the introduction of a joint/coordinated assessment procedure across multiple EU member states, as well as improved transparency for the public regarding clinical trials and their results.
As of January 31, 2023, new applications for interventional clinical trials must be submitted via CTIS. By January 31, 2025, all clinical trials that were submitted and are ongoing under the old legislation (EudraCT) must be transferred to CTIS.
What are the challenges of submitting via CTIS?
Initial experience with the application process shows that the new system presents several challenges for applicants:
medicinal product First of all, the European Medicines Agency (EMA) offers an overwhelming array of training resources on CTIS: training modules, a handbook, guidelines, newsletters, a Questions & Answers document, webinars, etc. It is important to allocate the necessary resources for this training.
Another time-consuming factor in the application process is the sheer volume of documents required for submission. On the one hand, all documents for all countries must be processed and uploaded simultaneously for both authorities and ethics committees. On the other hand, transparency requirements necessitate the creation of a second set of documents that comply with publication standards, meaning personal data and commercially confidential information must be redacted in these versions.
Furthermore, the deadlines for submitting supplementary documents or responding to queries are significantly shorter compared to the former EudraCT application process. Applicants are granted a maximum of 10 days during the validation phase and a maximum of 12 days during the evaluation phase, which includes weekends and public holidays! This requires thorough organization and the best possible preparation in advance, as well as daily monitoring of the CTIS portal, as applicants do not receive email notifications regarding incoming queries.
The current technical issues that the EMA is continuously working on should also not be underestimated. A list of current issues (Clinical Trials Information System List of known issues for Sponsor Users) is published by the EMA. Applicants are well-advised to be aware of these technical issues and to involve the EMA helpdesk if necessary when problems arise. Consequently, the time required for the application process increases accordingly.
What prerequisites must be met in order to set up a clinical trial in CTIS?
To begin as an applicant in CTIS, an EMA account and, if applicable, access rights or assigned roles granted by the sponsor administrator are initially required. This may include the role of "Preparer" and/or "Submitter" for all parts of the application dossier or only for specific sections: Part I (all fundamental scientific data), Part II (country-specific documents such as patient information and trial site suitability), and/or the quality dossier (Q-IMPD).
The CTIS system is linked to other EMA systems, such as the Organisation Management Service (OMS). If the organizations to be entered in CTIS (e.g., the sponsor and trial sites) are not yet registered in OMS, they must first be registered via a change request in OMS. The registration process for a new organization in OMS takes approximately five to ten working days.
The same applies to the investigational medicinal products and auxiliary medicinal products to be used, provided they are not yet authorized in the EU. These must be registered in the eXtended EudraVigilance Medicinal Product Dictionary (XEVMPD) database in order to be accessed within CTIS.
Furthermore, when submitting the application, it must be taken into account that referencing a quality dossier (Q-IMPD) that has already been submitted for another study is only possible if it has already been submitted within CTIS. Referencing an IMPD that was submitted and evaluated in a EudraCT study—i.e., under the previous legislation—is not possible. In this case, the Q-IMPD must be submitted in full.
What needs to be considered when transferring an ongoing study (transitional trials)?
January 31, 2025, is the deadline by which all studies authorized under the former legislation must be transitioned into CTIS. This means that all clinical trials with at least one active trial site remaining at that time must have obtained authorization in CTIS in order to continue.
To prepare for a transfer from EudraCT to CTIS, it may be necessary to harmonize the protocol, investigator's brochure, and quality dossier (Q-IMPD) across all participating EU countries. This should be applied for as a substantial amendment under the previous legislation.
Furthermore, adjustments required by the Clinical Trial Regulation may also need to be submitted in advance and must be approved by all countries.
Only after the completion of all ongoing procedures under the former legislation can an application for transition to the new Regulation (Clinical Trial Regulation) be submitted. This is a separate, independent application process involving a renewed assessment of compliance with the requirements of EU Regulation 536/2014 (Clinical Trial Regulation).
The application process for the transfer is evaluated within 60 days. During this time, queries may also be raised by the authority or ethics committee, which can extend the total duration of the process to up to 106 days.
Early initiation and preparation for the transition process are therefore essential in order to be able to continue an ongoing study even after the deadline of January 31, 2025.
Where can I get support for my CTIS submission?
Beate Beime Pharma Consulting has extensive experience in submitting clinical trials for medicinal products via CTIS and can assist you with:
Preparation of documents for upload: public (redacted) and non-public versions, nomenclature
Review of documents for CTR compliance
Creation of the cover letter, list of changes, and similar documents
Handling of document uploads, including metadata processing and filling in fields in the capacity of a "Preparer": Part I, Part II, and/or Q-IMPD
Managing submissions via CTIS in the capacity of a "Submitter": Application Submitter, Notification Submitter, CT Results Submitter, ASR Submitter
Daily monitoring in CTIS regarding incoming information: Requests for Information (RfIs), status changes, or authorizations, and prompt forwarding of this information
Timely processing of RfIs
Maintenance of authorization status: timely notifications in CTIS, processing of modifications, addition of Member States, Annual Safety Reports
Transition of currently ongoing trials into CTIS (transitional trials)
Sources:
EMA