Updates to transition instructions for clinical trials

The European Medicines Agency (EMA) recently published an update and guidelines on the transition of clinical trials, i.e. the implementation of EU Regulation 536/2014. In the transition, studies from the Clinical Trials Directive (CTD) are transferred to the Clinical Trials Information System (CTIS) portal, ensuring that they can be processed in accordance with the Clinical Trials Regulation (CTR) in the future. The transition must be concluded by 30 January 2025 for clinical trials that have at least one active site in the EU region on that date. Active site refers to the follow-up phase of a trial as well as any trial-specific intervention that has not yet been carried out. The results of other trials can still be submitted to the EudraCT database.

The new transition instructions are available on the European Commission’s website.

The transitioned clinical trials must meet the minimum requirements of the CTR regarding transparency and marking of the trial category. No new documents need or may be placed in the application. Instead, the documents must already be reviewed and approved by the authorities to the extent that approval is required. The maximum timeline for the transition procedure for multinational trials is 22 days.

In terms of transparency, the sponsor must assess which documents may be fully public and which must be made available in a separately modified version by redacting sections considered to be commercially confidential (for more information, see EMA guidelines). There is no need to update the templates at this stage, nor will there be need to retrospectively create a suitability form for the trial facilities of any existing sites. 

Key points in the new update and transition

Pre-transition considerations: 

• The multinational scientific sections of Part I have to be harmonised between the participating countries and approved under the CTD. Alternatively, country-specific differences can be compiled in the same protocol (so-called consolidation) if harmonisation cannot be achieved due to differences in legislation. Instructions are available on the website of the Clinical Trials Coordination Group (CTCG) (under Transitional Trials). The consolidated protocol does not require prior approval under the CTD.
• There should be no ongoing assessments in the participating countries at the time of the transition.

Transition in practice:

• Trials are transitioned to CTIS (Clinical Trials Information System) “Transitional trial” needs to be ticked in the application, and the EudraCT number of a CTD trial must be included to ensure the application will be correctly directed in the CTIS programme in the future. 
• The CTCG website above contains instructions for applicants and a template for the cover letter to facilitate the process. The cover letter has to include the ethics committees that have approved the study and the earlier EudraCT number of the trial. The sponsor must also check and declare that the clinical trial is in line with the requirements for transition trials and the authorisation given under the CTD. If the trial has even partly been involved in the Voluntary Harmonisation Procedure (VHP), its Reference Member State should be indicated. In other multinational studies, the sponsor should propose a reporting Member State for further evaluation.
• Only active clinical trial sites need to be included in the transition phase. It is not necessary to list the sites that have already been closed during the trial.
• Part I should include the following documents: protocol (harmonised/consolidated), researcher’s information package (investigator’s brochure or summary of product characteristics), documents related to good manufacturing practice (GMP), investigational medicinal product dossier (IMPD) and documents related to auxiliary medicinal products required for the trial. For multinational trials, document versions that have been approved in all participating countries must be included. 
• Part II (MS-specific part) needs to include the latest authorised versions of the subjects’ information sheets and informed consent forms. Instructions are available on the Tukija website (in Finnish).
• Temporarily halted clinical trials must also be transitioned. In such cases, the sponsor must submit a new notification immediately after the transition decision, stating these trials as halted.

After the transition:

• Once the transition has been completed, the requirements of EU Regulation 536/2014 will apply even if they are not stated in the protocol. Further trial activities take place on CTIS.
• Other documents required by the Regulation are to be submitted at the first substantial modification phase after the transition (excluding the suitability form for existing trial sites).
• The trial site ‘suitability form’ is filled in only for the sites to be added when a country is added. This cannot be done in the connection with a transition decision.
• If investigational medicines and auxiliary medicines have already been labelled, no changes are necessary. Existing labels may also be used until new labels complying with the Regulation have been approved under the first substantial modification and new batches of the investigational medicine are manufactured and/or (re)labelled.
• If recruitment of trial participants has ended, there is no need to change patient information sheets or similar to the format specified in the Regulation.
• If it is anticipated that an urgent amendment will be necessary following the transition, the transition cover letter can already contain information about this. In this case, an effort will be made to carry out the transition procedure even faster than in 22 days. However, despite the incomplete process, the sponsor must take the necessary measures to ensure the safety of the subjects. Transitions may also be withdrawn either by the sponsor’s decision or at the recommendation of an authority and amended in accordance with the Directive before the expiration of the transition period. A new transition application must then be submitted as soon as possible, before 31 January 2025.

As there are hundreds of trials in Finland that need to be transitioned in accordance with the Regulation, Fimea recommends that the transition be carried out at an early stage.

Read more:

Fimea web page: Clinical Trials Regulation & CTIS