The Clinical Trials Information System (CTIS) is the central EU-wide database and submission portal for clinical trials of medicinal products for human use in the European Union. It was introduced under EU Regulation 536/2014 on clinical trials and is gradually replacing the previous national systems as well as the EudraCT database. CTIS enables sponsors to submit a single application for clinical trials in multiple EU Member States, thereby creating a harmonized, transparent authorization process for all of Europe.
Background and Legal Basis
EU Regulation 536/2014 entered into force on January 31, 2022, and requires sponsors to submit all new clinical trials via CTIS. A three-year transition period allowed for the parallel use of the old national system, which ended on January 31, 2025. Since that date, all clinical trials—whether new applications or ongoing studies—must be managed via CTIS. The system is operated by the EMA in cooperation with the national authorities of the Member States and is publicly accessible via the EU portal. The goal is full transparency: all essential documents of a clinical trial—from approval to the final report—are publicly viewable, provided there are no legitimate confidentiality interests.
Submission Process and Distribution of Roles
In the CTIS workflow, the sponsor submits a single application for a clinical trial, which is evaluated simultaneously by a Reporting Member State (RMS) and all Member States Concerned (MSCs). Part I of the application contains the scientific-regulatory information (protocol, IMPD, investigator’s brochure) and is evaluated in a coordinated manner by the RMS. Part II contains the national, ethical-local aspects (informed consent, recruitment methods, patient compensation) and is reviewed by the respective national authorities and ethics committees. The total approval period is 45 days for straightforward studies but can be extended for complex studies or in the event of queries. CROs with EU expertise support sponsors with technical submission, workspace management, and communication with authorities within CTIS.
Transparency and Public Accessibility
A core principle of CTIS is the comprehensive transparency of clinical research. All application documents, approval decisions, protocol amendments, and final reports are published in the public section of the CTIS portal. This represents a paradigm shift compared to the previous system, in which many documents were not publicly accessible. Exceptions are possible if confidentiality interests—e.g., commercially sensitive information—can be demonstrated. The increased transparency is intended to strengthen trust in clinical research, avoid duplicate studies, and facilitate the secondary use of research results.
A particular challenge in CTIS is the management of national requirements in Part II. Although Regulation 536/2014 aims for extensive harmonization, Member States can maintain their own requirements in certain areas—such as patient compensation, language versions of the informed consent, or national ethics committee requirements. Sponsors and CROs must take these national specificities into account when designing the application to avoid queries and delays.
Challenges in CTIS Implementation
The introduction of CTIS was associated with significant technical and operational challenges. Many sponsors and CROs initially reported usability problems, unclear workflow steps, and time-consuming onboarding phases. The EMA has continuously developed the system since its go-live in 2022 and has regularly implemented updates. For CROs with a large study portfolio, CTIS means a significant training and process effort: regulatory affairs teams must be familiar with the submission workflows, document formats, and the different national requirements of the participating Member States. The complete replacement of national systems by CTIS is a major step toward the harmonization of clinical research in Europe.
The migration of existing EudraCT studies to CTIS represented a significant operational burden for many sponsors. Data migration was time-consuming, especially for ongoing, complex studies with numerous protocol amendments and sites. CROs with specialized CTIS expertise helped their clients with the technical implementation. The EMA has provided extensive training and support materials to facilitate the transition—including live webinars, FAQs, and a dedicated CTIS helpdesk.
For the future, the EMA plans further integration of CTIS with other EU systems such as EUDAMED (medical devices) and the European Health Data Space. This networking is intended to improve the interoperability of regulatory data, safety information, and real-world evidence, and to facilitate cross-authority data analysis. For sponsors and CROs, this means that investments in digital regulatory processes and CTIS expertise will be critical for competitiveness in the long term.
Frequently Asked Questions
Must every clinical trial in the EU be submitted via CTIS?
Since January 31, 2025, CTIS has been the sole submission route for all interventional clinical trials with medicinal products for human use in EU Member States. Non-interventional studies (NIS) and purely national studies outside the scope of Regulation 536/2014 are exempt from this requirement. Sponsors from third countries (e.g., USA, Japan) require an EU sponsor or a legal representative based in the EU for submission.
What is the difference between CTIS and EudraCT?
EudraCT was the previous EU database for clinical trials, which required a national submission in each Member State concerned. CTIS completely replaces EudraCT and enables a single, harmonized submission for all EU Member States. EudraCT studies approved under the old Directive 2001/20/EC had to be migrated to CTIS or completed by January 31, 2025.
How long does approval via CTIS take?
The regular evaluation period is 45 days for studies without specific requirements. For studies with ATMPs (Advanced Therapy Medicinal Products) or other complex medicinal products, the period can be extended to 90 days. In the event of queries (Request for Information), the clock is stopped until the sponsor responds. Experience shows that well-prepared dossiers without open questions are approved significantly faster.