Since January 31, 2025, the Clinical Trials Information System (CTIS) has been the mandatory EU-wide platform for the submission, assessment, and supervision of all clinical trials with human medicinal products in the EU/EEA, in accordance with Regulation (EU) No. 536/2014. With the end of the three-year transition period, sponsors must manage all studies – new applications as well as ongoing trials – exclusively through CTIS. The system replaces EudraCT and national submission portals. It restructures the study lifecycle: RMS selection, Part I/Part II, and automatic transparency publication. Those who view CTIS merely as a submission portal underestimate its operational scope.
Key Points at a Glance
- CTIS full obligation since January 31, 2025 – no exceptions for ongoing studies.
- Validation in 10 days (extendable to 15 with RFI), Part I assessment in 45 days (standard), +50 days for ATMP.
- Synchronized planning of Part I, Part II, and RMS selection determines approval duration.
- An overdue RFI means withdrawal of the application – re-submission with a new validation period and new assessment cycles starting in all involved Member States.
What CTIS Is – and Why It Changes the Rules of the Game
CTIS is the central EU/EEA portal according to Regulation (EU) No. 536/2014. An application reaches all involved national authorities and ethics committees simultaneously. Structurally, the system comprises three workspaces: the Sponsor Workspace, the Member State Authority Workspace, and the public portal euclinicaltrials.eu. CTIS is operated by the EMA; scientific assessment is the responsibility of the Member States, in Germany by BfArM and PEI.
7 Steps from Application Preparation to Approval in CTIS
- Configure Organization and Role Matrix – EMA account, OMS entry, rights assignment for sponsor, CRO, investigators.
- RMS Pre-selection – Weigh indication, investigational medicinal product type, and regulatory capacities.
- Compile Dossier – Protocol, IMPD, investigator brochure for Part I; country-specific documents for Part II.
- Synchronize Part I and Part II – Consistency check between protocol, IMPD, and informed consent documents.
- Submit Application in CTIS – Finalize language, CCI markings, and deferral justifications.
- Await Validation – 10-day period (extendable to 15 with RFI during validation) according to Art. 5 para. 3 of Regulation (EU) No. 536/2014.
- Process RFIs and Receive Approval – Part I assessment within 45 days (Art. 6); study start only after approval of both parts by each Member State.
The Two-Part Application: Strategic Planning for Part I and Part II
Part I bundles core scientific and medicinal product data (protocol, IMPD, investigator brochure) and applies uniformly to all Member States. Part II covers country-specific aspects: ethical opinions, recruitment plans, local informed consent documents. Errors in Part I affect all countries simultaneously. Isolated correction paths do not exist.
Case Study from Our Practice: A sponsor with a multinational Phase II program submitted Part I without a synchronized Part II. The RFI arrived in week 3, the assessment period was interrupted, and the study start was delayed by eleven weeks. Cause: diverging endpoint descriptions between the protocol and country-specific patient information. In our submission experience, the vast majority of all Part I RFIs stem from precisely such inconsistencies between the protocol, IMPD, and informed consent documents.
Part I-only Application: When It Makes Sense
Part I can be submitted alone if site selection is still open or contract negotiations are ongoing. Part II must be fully resubmitted for each Member State before the study begins.
RMS Selection: The Underestimated Strategic Decision
The choice of the Reporting Member State determines the assessment pace, communication quality, and regulatory depth of the Part I assessment. You propose the RMS in the application, and this RMS coordinates the scientific review for all involved Member States. Capacities, indication expertise, and response times vary significantly among the 30 EU/EEA authorities. BfArM and PEI regularly act as RMS – PEI particularly for ATMPs, vaccines, and blood products. For ATMP studies with PEI as RMS, we generally observe the full utilization of the +50-day extension according to Art. 6 para. 7. Plan for this time.
Deadlines, Validation, and RFI Management
The CTIS workflow follows a strict logic of deadlines. RFIs are the most common cause of avoidable delays.
| Phase | Deadline | Legal Basis |
|---|---|---|
| Validation by RMS | 10 days | Art. 5 para. 3 |
| Part I Assessment (Standard) | 45 days | Art. 6 para. 4 |
| Part II Assessment per MS | 45 days | Art. 7 |
| RFI Response Deadline Sponsor | max. 12 days | Art. 6 para. 8 |
| Assessment Extension (ATMP, Biological) | + 50 days | Art. 6 para. 7 |
| Decision after Assessment | 5 days | Art. 8 |
In the event of an RFI, the assessment period is suspended until the sponsor’s response. If the 12-day response period expires unused, the application is considered withdrawn. A complete re-submission then becomes necessary – including a new validation period and new assessment cycles starting in each involved Member State.
Seven Common Sources of Error in Initial Submission
- Inconsistencies between Protocol and IMPD – differing dosages, endpoints, or inclusion criteria.
- Blanket CCI Markings without Individual Justification – routinely rejected by the RMS.
- Missing Synchronization Part I/Part II – patient information contradicts the protocol.
- Incomplete OMS Registration – investigational sites or sponsor representatives not registered in the EMA Organization Management System.
- Incorrect Language Assignment – Part II documents not in the official language of the respective Member State.
- Incomplete Role Matrix – access rights for co-sponsor or CRO granted only after submission.
- Unclear Deferral Justification – publication deferral without a comprehensible patent or competitive strategy.
Transparency Obligations: What CTIS Publishes Automatically
CTIS automatically publishes approved clinical trials and associated documents on euclinicaltrials.eu, provided that neither Commercially Confidential Information (CCI) nor personal data prevent it. Justify CCI classifications precisely and document-specifically at the time of submission. Blanket markings are routinely rejected by the RMS.
Deferrals allow for a temporary postponement of sensitive data, for example, to protect ongoing patent strategies. Annual Safety Reports and Clinical Study Reports are also submitted via CTIS and become visible on the public portal.
Role Management and System Access
Access requires an active EMA user account and an organization registered in EMA Account Management. Within the Sponsor Workspace, you can assign granular rights to internal employees, contracted CROs, investigators, and subcontractors. A CRO can act as an authorized representative and process applications independently.
Configure the role matrix completely before the first application is submitted. Subsequent adjustments are subject to documentation requirements and must remain traceable in the audit trail.
CTIS in the Study Lifecycle: Post-Approval Obligations
Approval initiates the operational reporting obligation. Sponsors must document study start, first recruitment date, and study end within specified deadlines. Substantial Modifications are processed via a formal amendment application with its own assessment procedure. Annual Safety Reports must be submitted annually, and the Clinical Study Report according to Art. 37 within one year after study end. Failures lead to regulatory measures and reputational risks.
Mediconomics supports sponsors from Europe, USA, Switzerland, UK, and Denmark from the strategy phase to CSR submission – with a focus on oncology, ATMP, rare diseases, and Phase I to III programs. Arrange a free initial consultation.
Frequently Asked Questions
- When does the CTIS obligation apply to ongoing studies?
- Since January 31, 2025, all clinical trials with human medicinal products in the EU/EEA are exclusively conducted via CTIS. The three-year transition period since the entry into force of Regulation (EU) No. 536/2014 on January 31, 2022, has expired. Studies originally approved under the CT Directive 2001/20/EC and continuing beyond the cut-off date are also affected. Sponsors who missed the transition step must transfer the trials immediately.
- Can a sponsor freely choose the RMS?
- The sponsor proposes a Reporting Member State in the application. Final confirmation is made by the involved Member States. If the proposed RMS declines, the Member States decide jointly. Indication, investigational medicinal product type, approval history, and regulatory capacities should be considered in the decision. A well-founded justification in the cover letter increases the acceptance of the proposal.
- What happens if an RFI is not answered in time?
- Requests for Information suspend the assessment period according to Art. 6 para. 4. If the sponsor does not respond within the set deadline (max. 12 days), the application is considered withdrawn. A complete re-submission will be required. Incomplete responses lead to further RFIs. We recommend preparing RFI responses internally with clear responsibilities and short approval cycles.
