Submission of Safety Information in Clinical Trials of Medicinal Products
On 31 January 2022, Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC (also known as the Clinical Trial Regulation, CTR), entered into force, along with Commission Implementing Regulation (EU) 2022/20 of 7 January 2022, laying down rules for the application of Regulation (EU) No 536/2014 of the European Parliament and of the Council as regards setting up the rules and procedures for the cooperation of the Member States in safety assessment of clinical trials.
For all clinical trials approved under Regulation (EU) No 536/2014, the obligation to report to HALMED no longer exists, and all procedures are now carried out via Clinical Trials Information System (CTIS) and EudraVigilance (EV).
Regulation (EU) No 536/2014 had foreseen a transitional period of three years, which ended on 30 January 2025. By that date, all clinical trials on medicinal products previously approved under Directive 2001/20/EC had to transit to the new legal framework.
Regarding the reporting on safety information in clinical trials approved under Regulation (EU) No 536/2014, the obligations of the sponsor of a clinical trial or its representative are published on the European Medicines Agency (EMA) website. Eudralex Volume 10, which provides guidelines on conducting clinical trials in the European Union, is published on the European Commission’s website. The said documents contains Questions and Answers Document - Regulation (EU) 536/2014 as well, explaining the practical application of Regulation (EU) No 536/2014 in more detail.
Instructions for national specificities related to CTIS are available on HALMED’s website, under the section About HALMED/Central Ethics Committee (CEC)/Instructions for Applicants.
For clinical trials conducted in accordance with Regulation (EU) No 536/2014, sponsors of clinical trials are required to pay a fee for safety assessment in clinical trials to HALMED only if Croatia is the Member State leading the safety assessment for a specific investigational medicinal product (referred to as the safety assessing Member State, or saMS). These services are included in HALMEDs price list, under the item 11. Pharmacovigilance:
- Safety assessment in clinical trials (saMS);
- Safety assessment in clinical trials (saMS) for active substance included in different sponsors clinical trials.
For medicinal products that were investigated in clinical trials approved under Directive 2001/20/EC and finalised before the end of the transitional period, i.e. before 30 January 2025, the obligation to submit a Development Safety Update Report (DSUR) to HALMED still applies. The final DSUR that needs to be submitted is the one that covers the period in which the final study report was completed. In that case, DSUR should be submitted electronically, along with a cover letter that specifies the name and the protocol number of clinical trials conducted in Croatia. The cover letter should be manually signed and scanned, or signed using an electronic signature. DSUR should be submitted to HALMED within 60 days from the data lock point of the DSUR. The fee for this safety assessment procedure remains unchanged. As HALMED reports to CEC on received DSURs during regular CEC meetings, it is sufficient to send DSUR to the email address ispitivanja@halmed.hr, with the cover letter addressed to HALMED. HALMED also circulates the written report on the received DSURs to the Ministry of Health.
