What is the Clinical Trial Information System (CTIS)?
With the introduction of EU Regulation 536/2014 (Clinical Trials Regulation), the Clinical Trials Information System (CTIS) was established as a new tool for clinical trials of medicinal products in the EU. It is an electronic portal for the submission, evaluation, and monitoring of clinical trials, as well as a database for the public to search for information on approved clinical trials.
CTIS enables the centralized submission of clinical trial applications in up to 30 EU/EEA countries simultaneously with a single application. This includes submissions to both the national regulatory authorities and the ethics committees.
The rationale behind this new system is the introduction of a common/coordinated evaluation process across several EU member states, as well as the enhancement of transparency for the public regarding clinical trials and their results.
As of January 31, 2023, new applications for interventional drug trials must be submitted through 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 involved in submitting an application through CTIS?
Initial experiences with the application process show that the new system presents some challenges for applicants:
First of all, the European Medicines Agency (EMA) offers a truly extensive range 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 aspect of the application process is the enormous volume of documentation required to complete the application. First, for all countries, all documents must be processed and uploaded simultaneously for both the regulatory authorities and the ethics committees. On the other hand, due to transparency requirements, a second set of documents must also be prepared for each jurisdiction that meets the requirements for publication; that is, personal data and confidential business information must be redacted in these versions.
Furthermore, the deadlines for submitting additional documents or responding to questions have been significantly shortened compared to the previous 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. This includes weekends and holidays! This requires good organization and the best possible preparation in advance, as well as daily monitoring of the CTIS portal, since applicants do not receive email notifications regarding incoming questions.
The current technical issues, which the EMA is continuously working to resolve, should not be underestimated. The EMA publishes a list of the current issues (Clinical Trials Information System List of Known Issues for Sponsor Users). Applicants are well advised to be aware of these technical issues and, if necessary, to contact the EMA Help Desk for assistance. Consequently, the time required to submit an application increases.
What requirements must be met in order to create a clinical trial in CTIS?
To get started as an applicant in CTIS, you first need an EMA account and, if applicable, access rights or a role assigned by the sponsor administrator. This may include, for example, the role of “Preparer” and/or “Submitter” for all parts of the application dossier or only for individual parts: Part I (all basic scientific data), Part II (country-specific documents such as patient information and site eligibility), and/or the quality dossier (Q-IMPD).
The CTIS system is linked to other EMA systems, such as the Organization Management Service (OMS). If the organizations to be entered in CTIS (e.g., the sponsor and the trial sites) are not yet registered in OMS, they must first be registered in OMS via a change request. The registration process for a new organization in OMS takes approximately five to ten business days.
The same applies to investigational and auxiliary medicinal products to be used, provided they have not yet been authorized in the EU. These must be registered in the XEVMPD (eXtended EudraVigilance Medicinal Product Dictionary) database in order to be accessible in CTIS.
Furthermore, when submitting the application, please note that a reference to a quality dossier (Q-IMPD) that has already been submitted for another study is only possible if it has already been submitted to CTIS. It is not possible to reference an IMPD that was submitted and evaluated as part of an EudraCT study—that is, under the previous legislation. In such cases, the Q-IMPD must be submitted in its entirety.
What should be considered when transferring an ongoing study (transitional trials)?
January 31, 2025, is the deadline by which all studies approved under the old legislation must be transferred to CTIS. This means that all clinical studies in which at least one trial site is still active as of that date must have approval in CTIS in order to continue.
In preparation for a transfer from EudraCT to CTIS, the protocol, the investigator’s brochure, and the quality dossier (Q-IMPD) may need to be harmonized across all participating EU countries. This should be submitted as a “substantial amendment” under the old legislation.
In addition, any amendments to the Clinical Trial Regulation must be submitted in advance and must be approved by all countries.
Only after all ongoing procedures under the old legislation have been completed can an application be submitted to transition to the new regulation (Clinical Trials Regulation). This is a separate, standalone application process that involves a new review to ensure compliance with the requirements of EU Regulation 536/2014 (Clinical Trials Regulation).
The transfer application process is reviewed within 60 days. During this process, the authorities or ethics committee may ask for additional information, which means the process can take up to 106 days in total.
It is therefore essential to begin the transfer process and make the necessary preparations well in advance in order to be able to continue a study that is already underway even after the January 31, 2025, deadline.
Where can I get help with my CTIS submission?
Beate Beime Pharma Consulting has experience submitting clinical drug trials via CTIS and can assist you with:
Preparing documents for upload: public (redacted) and non-public versions, naming conventions
Verification of Documents for CTR Compliance
Preparation of the cover letter, list of changes, and similar documents.
Handling of document uploads, including metadata editing and filling out the fields in the “Preparer” role: Part I, Part II, and/or Q-IMPD
Submission via CTIS in the role of “Submitter”: Application Submitter, Notification Submitter, CT Results Submitter, ASR Submitter
Daily monitoring in CTIS of incoming information—such as requests for information (RfI), status changes, or approvals—and the prompt forwarding of this information
Timely Processing of the RfI
Maintaining Approval Status: Timely Submissions in CTIS (notifications), Processing Changes (modifications), Adding Member States, Annual Safety Reports
Transfer of Currently Ongoing Trials to CTIS (Transitional Trials)
Sources:
EMA