On 31 January 2022, the anticipated European Union (EU) Clinical Trials Regulation 536/2014 (EU-CTR) came into effect, replacing the long-standing European Union Clinical Trials Directive 2001/20/EC (EU-CTD) legislation that regulates the clinical trial landscape in the EU and European Economic Area (EEA). With the objective of increasing transparency and ensuring higher standards for patient safety, the new EU-CRT harmonizes the submission, assessment, and supervision of clinical trials with new directives and guidelines. With these massive regulatory changes taking effect now in EU, below we will highlight some the more significant guidelines that way dictate how clinical trials should be conducted and what health sciences companies can expect going forward, particularly where support from language service providers will prove essential.

Background on the EU-CTR

Since its introduction in 2001 and full implementation in 2004, the EU-CTD has been the regulating doctrine for all clinical trials conducted in the EU. In contrast to the newly adopted EU-CTR, which replaces it, this previous legislation was largely decentralized in nature and left regulatory submissions, approvals, communication, and management of clinical trials and clinical trial applications (CTAs) to be carried out at the EU member state level. Now, following approval from the European Medicines Agency (EMA) Management Board and an independent audit by European Commission (EC), the new ED-CTR, originally introduced in June of 2014, has come into full effect, and is slated to regulate all clinical trials and CTAs in the EU and EEA by January of 2025.

Digital Clinical Trial Regulation

The newly established EU-CTR introduces much needed reform for regulating clinical trials in the EU and EEA, with the main objective of harmonizing the entire regulatory process by introducing a new centralized digital portal and database. As a defining operational change to Europe’s regulatory system, the establishment of the Clinical Trial Information System (CTIS) serves as a single-entry point for regulators and sponsors to submit and regulate clinical trial data.

Among the many benefits of instituting an EU-wide system for managing all things clinical trial-related, CTIS has been designed to:

  • Enable the submission of a universal application via a single online submission platform, eliminating country-specific application requirements
  • Streamline all communication between the Member States Concerned (MSC) and the sponsors involved to a single channel
  • Provide a common destination where sponsors to submit any trial-related notifications, updated results, reports, and so on.

Furthermore, under the EU-CTR, the approval of applications at a multinational level comes down to one decision that considers both a scientific and ethical point of view. Specifically, one application is submitted via CTIS to all MSCs, and one decision is made based on the submission of a core scientific research data dossier and country-specific documents such as informed consent documents and site suitability information. Collectively, this CTIS platform is the backbone of the EU-CTR and has been designed to create a more suitable and efficient environment for conducting clinical trial throughout EU and EEA member states.

Safety and Transparency

With the establishment of EU-CTR and the CTIS, the EMA regulatory body is further aiming to promote transparency on clinical trial data and uphold the highest possible standards of safety for patients involved in the trials. To meet this objective, EU-CTR has added features to ensure that all information in the CTIS database is publicly accessible, unless confidentiality is required to protect personal data or private communications between EU members.

To uphold safety standards and streamline safety reporting in clinical trials, the EU-CTR has updated definitions and requirements for safety reporting and introduces strict guidelines for promoting pharmacovigilance through a database called EudraVigilance (EVDBMS), which serves as the EMA’s management database for reporting and evaluating adverse reactions to medicines undergoing clinical trials in Europe. First, EU-CTR outlines that not all adverse events (AE) and serious adverse events (SAE) are reported or recorded and trials involving more than one investigational medical product (IMP) require an annual safety report to a submitted via the CTIS. Next, suspected unexpected serious adverse reactions (SUSARs) must be reported via the EVDBMS.

Impact on Ongoing Clinical Trials and CTAs

Since all eligible clinical trials in the EU and EEA will be under the supervision of the EU-CTR by 31 January 2025, a transition period has been established for both ongoing clinical trials and CTAs. In the instance of a clinical trials currently underway, sponsors have been allotted a 36-month period to conform to the EU-CTR. During this period, sponsors can expect no change in the activities, and datasets for clinical trials, however, change in the management of study start-up activities, RFI responses, and modifications to the CTA dossier will be required. For instance, one requirement calls for sponsors to answer all RFIs within 12 days regardless of the phase of the CTA (assessment or validation). Also, country-specific timelines for RFIs have been replaced with uniform assessment timelines to further harmonize the window for conducting clinical trials and streamline communication between MSCs and sponsors. For CTAs, the new guidance dictates that first-year sponsors may elect to follow the previous EU-CTD for a 12-month period until the end of January 2023, after which all CTAs must be in line with EU-CTR standards. Conversely, sponsors otherwise, and prior to January of 2023, have the choice of submitting CTAs via the new CTIS and under the EU-CTR.

Preparation for EU-CTR

With imminent change taking place in Europe’s clinical trial regulatory affairs, sponsors, and contract research organizations (CROs) can expect there to be adjustments in the timing and management during this transition period. With the new processes requiring a faster turnaround time to have documents prepared for submission, there will be a demand for a streamlined translation process to work against this tighter deadline. Similarly, with the mitigation of country-specific regulatory submissions and with the objective to increase transparency, the EU-CTR promotes the use of plain language for most documents. To meet this, it’s therefore crucial to work in collaboration with a reliable translation service provider that has the capability to scale up and be responsive throughout the approval life cycle. Learn more here about how CSOFT helps CROs and sponsors swiftly and effectively market their products in accordance with global regulatory standards!