Clinical Trials Regulation no 536/2014

The Clinical Trials Regulation no. 536/2014 will apply from 31 January 2022. The new regulation applies to all clinical trials of medicinal products for human use in the European Union. The new regulation does not apply to non-interventional studies.

The Clinical Trials Regulation no. 536/2014 will apply from 31 January 2022. The new regulation applies to all clinical trials of medicinal products for human use in the European Union. The new regulation does not apply to non-interventional studies.

The aim of the new regulation is to make the European Union more attractive destination for pharmaceutical research and development. The regulation harmonises different processes concerning the application for authorization, evaluation and supervision of clinical trials in the European Union and the European Economic Area.

  • 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

EU Clinical Trials Information System (CTIS)

The regulation allows the sponsor to submit one single application through the Clinical Trials Information System (CTIS) to all countries where the study is to be conducted, and the national competent authorities and the ethics committees will evaluate the application in cooperation. It will also be easier to extend existing clinical trials to other countries in the European Economic Area.

For more information, please contact the European Medicines Agency directly via [email protected].

Trainings

CTIS

The European Medicines Agency (EMA) has developed an online training program on CTIS.

In addition to the training program, a sponsor handbook has been published.

More information on the training and materials provided by CTIS and EMA can be found here.

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 new regulation provides for a transitional period of three years. Within one year, until 31 January 2023, sponsors may submit applications under either the new Clinical Trials Regulation or the current legislation (based on the Clinical Trials Directive). From 31.01.2023, the submission of applications under the new regulation will become mandatory. By 31 January 2025, all ongoing studies must comply with the requirements of the regulation and the study data must be transferred to the CTIS.

Applications under Directive 2001/20/EC

Applications under Directive 2001/20/EC must comply with the Directive and the corresponding national legislation.

Approval from the Ethics Committee for medical products and approval from the State Agency of Medicines are required before commencing a clinical trial of a medicinal product.

In order to obtain authorisation from the State Agency of Medicines, clinical trial application, consent of the head of the research center and the documents listed in the regulation of the Minister of Social Affairs "Conditions and Procedure for Conducting a Clinical Trial of a Medicinal Product" must be submitted. Electronic documents are preferred.

Medicinal Products Act and regulations of the Minister of Social Affairs:

Rules of procedure of medical ethics committee for clinical trials, a list of data to be submitted for obtaining approval, procedure for adoption of resolutions and format of application for obtaining approval

Procedure for reporting serious adverse events occurring in clinical trials

Conditions and procedures for conducting a clinical trial of the medicinal product

The decision will be made within 30 days in the case of phase II-IV trials, 60 days in the case of phase I trials and within 90 days in the case of gene therapy, cell therapy and the use of a genetically modified organism. The authorization includes, among other things, a study reference number from the State Agency of Medicines, which must be used in further correspondence concerning the study. The reference number is a five-digit number (xx-xxx), where the first two digits indicate the year and the last three the sequence number of the study in the database of the State Agency of Medicines.

Evaluation fees of an application for a clinical trial of a medicinal product are outlined in the regulation of the Minister of Social Affairs.

Safety reporting in studies that comply with the Directive is carried out as before: SUSARs are reported directly to the EudraVigilance database (it is not necessary to send them to the State Agency of Medicines), DSURs should be sent to [email protected].

Estonian legislation

In order to comply with the new regulation, changes will also be made in Estonian legislation.

Medicinal Products Act

Evaluation fees of an application for a clinical trial of a medicinal product

Ethics committee for medical products

Last updated: 01.04.2022