Current Edition

A Reflection on the European Regulatory Framework

Historically gaining regulatory approval across multiple countries within the European Union (EU) was segmented, excessively bureaucratic, and challenging to navigate. Sponsors had to submit clinical trial applications separately to national competent authorities (NCA) and ethics committees (ECs) in each country to gain regulatory approval to run a clinical trial. Individual countries dictated their own set of national submission requirements and gave local opinions on the trial design. The result of inconsistent feedback left Sponsors with the challenge of unifying recommendations within a single global protocol often leading to multiple protocol amendments or country-specific versions of the master protocol. These challenges subsequently resulted in inflated costs and long start-up timelines and the perception that the EU was a difficult place to run clinical research.

On 31 January 2022 the EU Clinical Trial Regulation (EU CTR) No 536/2014 came into effect and repealed the Clinical Trials Directive (CTD) 2001/20/EC and national implementing legislation in the EU Member States.1 The EU CTR is focused on ensuring high patient safety standards, collective decision-making on clinical trials and greater public transparency of clinical research, and aims to make the EU a more attractive place for conducting high-quality large-scale trials. There is a requirement to transition all clinical trials to the EU CTR by 31 January 2025 if they are still ongoing.

Streamlining the Regulatory Process

The EU CTR enables Sponsors to submit one multi-country application via a single online platform through the Clinical Trials Information System (CTIS) for approval to run a clinical trial in the EU and European Economic Area (EEA), making it more efficient to gain regulatory approval for multinational trials. The CTIS provides a single point of entry for clinical trial application procedures and publication of trial results over the life cycle of clinical trials run across the EU/EEA.

For multi-country clinical trial applications, a single, harmonised submission dossier is presented. The dossier is reviewed in two parts with the scientific assessment of the core documentation harmonised across all member states being led by one reporting Member State (part I) and ethical assessment of the country- and site-specific documentation (part II) completed by each country where the trial is to be conducted, creating a combined review and assessment process.

One of the principles of the EU CTR is that all submitted documents will be publicly available and the CTIS allows for searchable clinical trial information. CTIS enables redaction of documents as the method to protect personal data (PD) and commercial confidential information (CCI), if those are included in the documents. Having a single portal where the whole regulatory and ethical dossier of a trial is available has led to greater transparency of information.