The European Union (EU) Clinical Trials Regulation Nº 536/2014 came into force on 31 January 2022, repealing the Clinical Trials Directive and improving the harmonisation of clinical trials regulation throughout the EU and European Economic Area (EEA). To implement this regulation, the EU introduced the Clinical Trial Information System (CTIS).
CTIS is the single-entry point for submitting clinical trial information in the EU/EEA and supports the flow of information between clinical trial sponsors and regulators. CTIS contains a secure workspace for sponsors, their delegates and authorities for the management of clinical trials. There is also a public area where detailed information can be accessed on all clinical trials conducted in the EU/EEA. CTIS is one of the most significant aspects of implementation of the EU CTR and has come with its own unique challenges.
Getting started with CTIS and OMS
CTIS interacts with several EU databases and systems. These are all managed by EMA and allow users to search for information on organisations and medicinal products which can be selected in CTIS.
Step 1: EMA user account creation
The first step to access the CTIS sponsor workspace is for users to have an EMA account.
- If users already use other EMA applications, they will already have an EMA account and their existing login details can be used to access CTIS
- If users do not have an active EMA account, an account would need to be created via the EMA Account Management Portal. The process is described on the EMA Account Management homepage. Creation of a new account can take up to 2 business days.
Users should complete their profile by adding their employer organisation, which would need to be registered in the Organisation Management Service (OMS) system.
Step 2: Organisation registration
The second step for organisations is to review the OMS. This system is in EMA’s SPOR portal and provides a single validated source of organisation data for CTIS, including organisation names and location addresses.
All organisations participating in a clinical trial should be registered in OMS to be selected in CTIS. This includes sponsors, co-sponsors, third party contractors (e.g., CROs), EEA trial sites and marketing authorisation holders. Once registered, a user can retrieve details for the organisation to populate in the clinical trial application in CTIS.
EMA has recently introduced the option of organisation registration directly in CTIS if organisations participating in a clinical trial are not yet or can’t be registered in OMS. However, organisations that are created locally in CTIS are not validated by EMA. Therefore, users are encouraged to keep in mind the OMS data quality standard set when they create their organisations in CTIS to reduce receipt of RFIs from assessing authorities regarding inaccurate data.
To understand whether an organisation is registered in OMS, users will first need to search for and view the full details of an Organisation and its locations in OMS.
If the user:
- Cannot find the organisation, they can create a brand new organisation
- Finds the organisation but not its location, they can submit a change request to add a new location to the organisation
- Finds both the organisation and its location, but either of these are not up to date, they can submit a change request to update the organisation and/or location data
- Finds the organisation with an active status but the location with an inactive status, they can submit a change request to update the organisation data or add new locations
To complete these actions, users should follow the instructions as described in the “E – OMS Change Requests” guidance document and include any relevant supporting documents with their change requests.
Submission of a new organisation or change request can take 5-10 business days for EMA validation.
Step 3: CTIS high level sponsor administrator registration
Once an organisation is registered in OMS, sponsor organisations must then register a high-level administrator via the EMA Account Management.
This high-level administrator plays an important role in CTIS user management as they are responsible for the allocation of business roles and permissions to users working for, or on behalf of, their organisation. There are no limitations on the number of high-level administrators.
To request this role, users should:
1. Access the EMA Account Management. Select “Manage Access” and “Request Access for Organisations”
2. Select the applicable organisation
3. A list of roles that can be selected for this organisation will be shown:
a. CTIS High Level Sponsor Administrator Role – user must select this role.
b. External Organisation Administrator – this is an optional “super user” role and can be requested once for an organisation. With this role sponsors can approve the First CTIS High Level Sponsor Administrator Role themselves as well as other roles related to European syste
4. An Affiliation Letter Template proving the organisation’s authorisation is required when submitting the request for this registration. Details to this registration process can be found in Module 07 of the CTIS Training Material Catalogue.
This step can take 2-3 business days for EMA validation.
Step 4: CTIS high level sponsor administrator – creating a trial
Once the sponsor high-level administrator is registered, the user will need to request and approve themselves as the “all trials” CT Administrator role in CTIS, which will allow them to have the permissions to create clinical trials, using the “+ New trial” button.
It is very important that the sponsor entity who creates the trial is the same sponsor entity to be used on the protocol and other study documents. Please note, permissions to create a trial are retained by the sponsor unless a CT Administrator for “All Trials” is provided to the chosen representative.
Once a trial is created, the sponsor high-level administrator can delegate roles to the representative based on study scope e.g., CRO CT Administrator (trial specific).
Interface with XEVMPD: Medicinal product registration
The extended EudraVigilance medicinal product dictionary (XEVMPD) includes all medicinal products that are authorised or in development in a clinical trial in the EU/EEA.
All products authorised and unauthorised investigational medicinal products, as well as auxiliary medicinal products must be included in CTIS as part of the clinical trial submission. It is important that products are registered in XEVMPD at a very early stage in the clinical trial submission preparation process otherwise they cannot be selected in CTIS during the CTIS application form. A placebo can be added manually in CTIS without resorting to registration in XEVMPD.
EMA offers detailed information on XEVMPD registration, usage, FAQs and training materials. These are referenced in the CTIS Sponsor Handbook.
Conclusion
Setting up clinical trials under the EU CTR and the implementation of CTIS represent pivotal changes in the European clinical trials landscape. These advancements are aimed at harmonising regulations, increasing transparency, and streamlining the submission and management of clinical trial data.
Embracing the EU CTR and CTIS is essential for conducting clinical trials within the EU and EEA. The increased transparency, regulatory coordination, and improved management of clinical trial data will ultimately benefit both sponsors and the broader healthcare community.
While the new regulation and CTIS come with their challenges, guidance and support are available to assist sponsors and organisations through the process. ICON’s CTIS experts draw from their wealth of experience to provide flexible CTIS support to sponsors who are new to CTIS and OMS, providing valuable insights and guidance for the best use of the system.
References
- https://health.ec.europa.eu/system/files/2016-11/reg_2014_536_en_0.pdf
- https://register.ema.europa.eu/identityiq/help/selfregister.html
- https://spor.ema.europa.eu/omswi/#/
- https://spor.ema.europa.eu/omswi/#/viewDocuments
- https://register.ema.europa.eu/identityiq/login.jsf
- Affiliation Letter Template
- https://www.ema.europa.eu/en/human-regulatory/research-development/clinical-trials/training-support/clinical-trials-information-system-ctis-online-training-modules
- https://www.ema.europa.eu/en/human-regulatory/post-authorisation/data-medicines-iso-idmp-standards/extended-eudravigilance-medicinal-product-dictionary-xevmpd-training
- https://www.ema.europa.eu/en/documents/other/clinical-trial-information-system-ctis-sponsor-handbook_en.pdf