Clinical Trials Regulation no 536/2014

• The EU Clinical Trials Information System (CTIS) will be used to submit clinical trial applications.
• One trial application = one set of documents.
• The Member States involved will jointly assess the application. Each Member State will decide whether to authorize the study or not.
• The application consists of two parts: Part I (common for all countries) and Part II (country-specific).
• There are clear deadlines for evaluating the application, which are also followed by the ethics committees.
• Simplified notification procedures that do not require sponsors to provide similar information to different authorities in different Member States .
• Clinical trials conducted outside the EU referred to in the application must comply with EU requirements.
• Increased transparency of clinical trials data.
• The Commission will have the right to inspect clinical trials in Member States and in third countries. 

Initial application

The clinical trial application consists of two parts: Part I (common for all Member States) and Part II (country-specific). Joint assessment applies to both clinical initial applications and applications for substantial modifications (SM). In a joint assessment, the Reporting Member State will prepare an Part I assessment report, which the other Member States Concerned can comment on, and add their own considerations.

The requirements for the application dossier are set out in Annex I of the Regulation no 536/2014.

The general requirements and templates for Part II documents are available in the European Commission's guide Eudralex vol 10.

Application for substantial modification

The Clinical Trials Regulation allows a sponsor to submit a single application through the Clinical Trials Information System (CTIS) to all countries where the trial is intended to take place. The application is then jointly assessed by the relevant national authorities and ethics committees. It also makes it easier to extend ongoing trials to other European Economic Area countries.

Guidelines

The European Medicines Agency (EMA) has developed an online training programme to introduce CTIS and provide supporting materials for submitting applications. This can be found on the EMA website HERE. 

In addition to the training programme, a handbook for sponsors has also been published.

Public database and interactive map in CTIS

CTIS also includes a public database and an interactive map of clinical trials in the European Union, available HERE. Among other things, the map allows you to see which trials are currently being conducted in Estonia and which of them are in the recruitment phase.

Using the search function, all trial sites matching the selected criteria are displayed as dots on the map. By clicking on a dot, additional information about the trials conducted at that site is shown, including investigator contact details.

More detailed information on trials can be found in the advanced search of the clinical trials database, where studies can be sorted by various criteria.

In addition, the portal allows Member States to jointly assess safety data from ongoing studies. This provides a better overview of the risk-benefit balance of investigational medicinal products.

All clinical trial documents to be reported by the sponsor, including notifications, substantial modifications, annual safety reports (ASRs), the final study report and the results, are submitted through the portal.

The exception is SUSAR notifications, which must be submitted directly by the sponsor to the EudraVigilance database.

The list of Part I documents can be found in EU Regulation no 536/2014 Annex I, points B to J.

Estonia has no specific requirements for cover letters.

See European Commission Eudralex vol 10 for various guidelines.

Country-specific requirements can be found in the European Commission Eudralex vol 10 Questions and Answers Document Annex II.

Starting on 27.04.26, country-specific patient facing materials must be submitted in Section R of Part II instead of Section D of Part I, except for mononational trials. English-language materials must still be submitted in Section D of Part I. For more detailed information, see question 1.24 in the Q&A document. In Estonia, it is mandatory to submit patient facing materials in Estonian (RavS § 993(1)). The trial sponsor is responsible for the quality of translations into other languages, and their use is recommended to be referenced in the application (e.g., in a cover letter).

We encourage the sponsors to share their plans with SAM if Estonia is to be proposed as a Reference Member State (RMS) in a clinical trial application. We can be reached by e-mail at [email protected].

All the important information can ba found from HERE. 

An appeal against a decision on the authorisation of a clinical trial may be submitted to the Medicines Agency within 30 days of notification of the decision in accordance with § 71(1) and § 75 of the Administrative Procedure Act. If the recipient of the decision wishes to challenge the decision before an administrative court, he or she may lodge an appeal against the decision with the Tartu Administrative Court within 30 days of notification of the decision, in accordance with § 7(1) and § 46(1) of the Code of Administrative Court Procedure.