CTIS supports clinical trials sponsors to apply for clinical trial authorisation in up to 30 European Union (EU) countries (member of states) with a single application process.
Clinical Trials (CTs) Regulation (EU) published on 27 May 2014 took over Clinical Trial Directive 2001 / 2004 which was one of the key initial transitioning in Clinical Trials regulatory framework in light of simplifying and harmonising procedures for the EU (multinational) clinical trial application submissions, while improving public data access availability including studies’ results.
Implementation of CT Regulation – 3 years transition period (Feb 2022- Feb 2025)
1 February 2023 – CTIS / CT Regulations are mandatory for all new trials.
This new platform brought many positive advancements, but also challenges, where some prospective gaps are gradually identified and jointly addressed.
CTIS users need to be registered either in a role of ‘Administrator’ or ‘Business’. Administrator roles are able to assign a role to other users within their organisation. Business roles, assigned by ‘administrators’ users’ are responsible during the life cycle of clinical trial. Administrator role can be high or medium level. High-level administrators are Sponsor administrators, requiring EMA validation. They can have organisation-centric approach, meaning they can manage all users within the organisation (Business roles and Medium- level Administrators). Medium-level ones are CT Administrators, assigned by High-level administrators. Trial- centric approach is also available and suitable for smaller organisations type of sponsor users and will not require EMA validation approach.
EU Portal holds two workspaces:
1. Sponsors
2. Authority
There is a public website which offers general public appropriate level of data accessibility for clinical research while supporting data transparency.
There are three types of applications:
1. Initial CTA
2. Additional MSC (member of state / country)
3. Substantial modification (Substantial Amendment)
A new Initial CTA application can be mononational (involving one member state country (MSC)) or multinational (involving more than one member state country (MSC)). In multinational applications reporting member state (RMS) needs to be selected. Member state country can express willingness to become RMS within 3 days of application.
Initial CTA application
For an Initial CTA application submission sponsors should consider the following:
- Validation (10- 25 days if there is a request for further information (RFI)) – the user will need to prepare cover letter, the proof of payment (in the various MSCs), the compliance with Regulation (EU) 2026/679 (GDPR), publication dates of the clinical trial information, with deferrals if applicable. The application needs to contain information about the number of participants that will be recruited at each member state country.
- Assessment (45-76 days)
- Part I – scientific
- Part II – national and patient facing documents review that could take more 19 days in case of request for additional information (RFI). Initially could be submitted only part I and part II can be submitted within 2 years.
- Evaluation displays information related to evaluation and assessment of Part I & II. This is the area for RFIs. There is Timetable which has an overview of the evaluation status and application progress. The reporting member state has up to day 10 to consolidate the considerations of the different member state countries.
- Decision (up to 5 days)
TheInitial CTA has four main sections with required fields:
- Form – sponsors can complete data and submit documentation relating to general clinical trials information, including the GDPR. They also have to add the member states which will be considered.
- Cover letter can’t be changed after submission.
- Proof of payment of fee -once member state is added into the member state counties (MSC), the Proof of Payment section appears with suggested amount, specified per each member state that will be involved in the study.
- Compliance with Regulation– GDPR document need to be uploaded to indicate the sponsor will comply with the data protection law.
- Member state countries (MSCs) – This section contains information about the number of subjects per member state and proposing reporting member state (RMS) (within 6 days of submission). In this section has to be completed information about Countries outside of the EU/ EEA or adding another member state (if applicable).
- Part I (Scientific) – Sponsors / Co- sponsors contact point information (Third party / CRO, Legal Representative, Scientific and Public contact) and uploading the following documents: protocol, clinical trial design, eligibility criteria, clinical conditions / therapeutic area, IB, IMP dossier(s), IMP labelling.
There are four roles of medicinal product that can be added: 1. Test (authorised or unauthorised), 2. Auxiliary (background treatments), 3. Comparator, 4. Placebo
- Part II (National and Patient facing) (+19 days in case of request for additional information (RFI)) – PIS, ICF, recruitment plan, clinical trial sites (PIs), recruitment arrangements, proof of Insurance, financial arrangements, GDPR, compliance with human tissue regulations. This section should contain specific information provided for each member state country. Relevant documents need to be uploaded.
Marketing authorisation applicants are required to submit Risk Management Plans (RMPs).
Withdraw Initial CTA – This could be done for all member state countries until conclusion of Part I (reporting data) is submitted. After the reporting date and while the Initial CTA is still under Evaluation and before decision by each MSC is issued, the CTA can be withdrawn from each MSC separately.
Re- submission Initial CTA – This can be done, with specifying EU trial number for the previous clinical trial application.
Transitional trials
1 February 2025 – All ongoing clinical trials (Transitional) need to be re- submitted via CTIS according to Clinical Trail Regulations. EudraCT continues to operate for reporting CT Directives and global end of trials. Global end of the trial and trial summary results should be uploaded via EudraCT.
Sponsors must transition a trial from EudraCT to CTIS if at least one of the following conditions is fulfilled:
• the trial authorised under the CT directive is going to be submitted to an additional EU/EEA member state(s).
• the EudraCT trial completion date is expected to be after 30 January 2025.
In addition, only trials that meet the following criteria can be transitioned:
• Interventional clinical trials in humans.
• Involve at least one site in the EU/EEA where the trial is still ongoing.
• No notification has been submitted regarding whether the trial has ended in the EU/EEA
In order to transition a trial from EudraCT to CTIS, an Initial CTA marked as a Transitional trial must be submitted. Once the draft Transitional trial application has been created, the following sections ‘Form’, ‘MSCs’, ‘Part I’ and ‘Part II’ have to be completed.
Member state countries (MSCs) may choose to authorise the trials within or in less than 60 days. However, MSCs can create RFIs on the transitional application (leading to a maximum period of 106 days review period, or further in the case of some types of investigational medicinal products). The sponsors are advised to submit their Transitional trials to CTIS early enough before the end of the transition period.
Medical Devices applications – CTIS does NOT apply yet and it is expected to be implemented in late 2025 or early 2026.
Author: Galina Petrikova
Date: 11 July 2024
