Blog Writer

Clinical Trial Regulation: Understanding the Significance of CTR No. 536/2014 and a Guide to Transitioning from CTD.

Jayne Hunt
Jayne Hunt
Principal Consultant, Regulatory Affairs

Jayne has over 30 years strategic & operational Regulatory Affairs expertise in pre & post marketing across the EU, UK, US, and other territories.

She has experience in multiple areas including ATMPs, biologics, small molecules, marketing authorizations and pre-marketing development activities.

This includes supporting interactions and meetings with regulatory agencies in Europe (National and EMA) as well as with the FDA & Health Canada.

Jayne holds a PhD in Biochemistry from the University of London.

Introduction.

Welcome to our exploration of the changing landscape of the European clinical trial processes following the implementation of the Clinical Trial Regulation (EU) No. 536/2014 (CTR). In this blog, we not only shed light on the critical aspects of CTR but also delve into the essential considerations for the transitioning from the traditional Clinical Trial Dossier (CTD) to the modernized CTR framework.

Q1: Are you aware of the impact of CTR?

I’m sure you are! Clinical Trial Regulation No. 536/2014 has ushered in a new era for clinical trials in the European Union and European Economic Area (EU/EEA). The regulation aims to simplify and harmonize the clinical trial application process across member countries and encourage clinical development within the EU. The transition period for the CTR came into effect on January 31st, 2022, at the same time as the launching of the Clinical Trials Information System (CTIS).

Q2: Do you know how and when to transition to CTR?

Key Timelines:

We’ve already passed the following milestones:

  • January 31st, 2022 – CTR came into effect, at the same time as the Clinical Trial Information System (CTIS)
  • January 31st, 2022 – the CTR repealed the Clinical Trials Directive, making it apply only up to 30th January 2025
  • From January 31st, 2023 – all new initial CTAs had to be submitted via CTIS / CTAs ongoing under the CTD could be optionally transitioned to the CTR.

And now, in the not-too-distant future:

January 31st, 2025 – compulsory requirement for all CTs ongoing under the CTD with an active site in the EU/EEA to be conducted under CTR: This means that there is not much time now to complete all the activities needed to transition any studies still being conducted under CTR by this point.

Why CTR Matters:

Clinical Trial Regulation No. 536/2014 represents a monumental shift in the approach registering clinical trials within the EU/EEA. Its importance lies in aligning the processes for the regulatory authority and ethics submissions across member states. Here’s why CTR is a game-changer:

  • Simplification and Harmonization:

By simplifying the submission package and harmonizing the competent authority and ethics submission into a single entry point (CTIS), the intention it is to reduce the administrative burden and accelerate the study start-up timelines for clinical trials in the EU.

  • Introduction of CTIS – A Single-Entry Point:

The Clinical Trials Information System (CTIS) as a single-entry point is revolutionary serving as a centralized platform for sponsors and regulators, facilitating:

  • The submission of the clinical trial application.
  • The dissemination of application data between member states
  • A repository for authority questions and responses.

This not only reduces the redundancy of multiple submissions and associated activities, but also enhances efficiency in the review process.

  • Universal and Country-Specific Documentation:

CTR introduces a two-part structure for Clinical Trial Applications (CTAs). Part I is universal across all countries and equates to the competent authority application of the CTD, while Part II is country-specific, aligning with the previous country specific ethics submissions. This dual structure simplifies the regulatory landscape for sponsors, providing a standardized foundation while allowing for necessary local deviations.

  • Clearly Defined Timelines:

The regulation establishes clear and defined timelines for the evaluation of clinical trial applications, providing  predictability on the timelines for both sponsor and regulatory authority activities.

Transitioning from CTD to CTR: A Step-by-Step Guide.

For any studies still being conducted under the CTD, a crucial consideration will be the prompt transition to the CTR.

Here’s a step-by-step guide to support the transition:

  1. Evaluate Your Current Clinical Trials.
  1. Evaluate Your Clinical Trials Being Conducted Under the CTD & Develop a Transition Plan:
    • Assess the status of your clinical trials that are ongoing under the CTD.
    • Confirm which countries will be complete or still active by 31 January 2023.
  1. Update Clinical Trial Documentation:
    • Craft a comprehensive transition plan that outlines the steps to be taken to update each ongoing clinical trial. Consider factors such as documentation updates such as protocol alignment, collation of Part II country-specific data the & timelines to complete the necessary amendment submissions, and communication with relevant stakeholders.
  1. Ensure CTIS Access and Pre-requisites:
    • Ensure that you have the necessary access to CTIS and fulfil any pre-requisites. This includes understanding the functioning of the Organizational Management System (OMS) and the Extended EudraVigilance Medicinal Product Dictionary (XEVMPD).
  1. Collaborate with Expert Service Providers:
    • Engage with experienced service providers like Arriello, who specialize in Clinical Services Operational support. They can offer invaluable assistance with Clinical Trial submissions, application oversight, and strategic/documentation services.
  1. Address Translation and Redaction Activities:
    • If your documentation requires translation or redaction, address these activities promptly. Ensuring that all documents are in compliance with CTR language and formatting standards is essential.

  2. Implement a Robust Oversight System:
    • Establish a robust oversight system for ongoing and new clinical trials. This includes monitoring compliance, addressing any issues promptly, and adapting to any further regulatory changes.

Conclusion:

Navigating the Clinical Trial Regulation (EU) No. 536/2014 requires a proactive and informed approach. The importance of CTR lies in its ability to create a more efficient, transparent, and harmonized environment for clinical trials in the EU/EEA. As you embark on the journey of transitioning from the traditional CTD to the CTR framework, meticulous planning, collaboration with experts, and adherence to timelines are key.

Arriello stands ready to assist you on this regulatory voyage. With a suite of services covering:

  • Clinical Trial submissions
  • Application oversight
  • Regulatory intelligence and more

We are your partners in ensuring a smooth transition and successful navigation through the evolving seas of clinical trials regulation in the EU/EEA.