By: Sarah Bly, Regulatory Science and Innovation and Matt Cooper, Executive Director, Therapeutic Strategy Lead, Oncology
The European Union (EU) presents a unique set of regulatory challenges and opportunities for clinical trials in oncology. The CRO landscape is rapidly evolving with the recent implementation of the EU Clinical Trials Regulation No 536/2014 (EU-CTR) and the launch of the Clinical Trials Information System (CTIS). This blog delves into the key aspects of the EU regulatory space and provides insights into navigating these changes effectively.
Regulatory Harmonization of Clinical Trials in the EU
The EU-CTR repealed the Clinical Trial Directive 2001/20/EC (CTD) and national implementing legislation in the EU Member States on 31 January 2022. This change marked a significant shift towards harmonizing clinical trial assessments, authorization, and supervision throughout the EU. The EU-CTR leverages a new portal and database called the CTIS, which enables a centralized electronic submission to replace multiple submissions, each with different dossiers. This harmonization aims to streamline processes, increase transparency, and foster innovation within the EU.
Key Benefits of the CTR and CTIS:
- Improved Information Sharing: Facilitates collective decision-making on clinical trials.
- Increased Transparency: Ensures that information on clinical trials is more accessible.
- High Safety Standards: Ensures the protection and safety of all participants in EU clinical trials.
The Critical EU-CTR Transition Deadline
The three-year transition period for clinical trials authorized under the CTD that are expected to continue beyond the critical deadline of 30 January 2025 are required to transition to the new EU-CTR via a transition application through the CTIS. This deadline is crucial because of the following:
- Transition of Ongoing Trials: Failure to transition will mean that the clinical trial cannot continue under the previous legal regime.
- Unified Submission Portal: The CTIS serves as a single-entry point for the submission, making the process more streamlined but requiring all stakeholders to adapt to the new system and interface.
- Enhanced Transparency: Post-deadline, all clinical trials will be subject to increased transparency under the harmonized assessment procedures, which aims to improve patient safety and public trust in clinical trials.
These impending changes underscore the importance of acting now to understand and adapt to the EU-CTR requirements to ensure smooth and compliant trial operations.
Accelerating Clinical Trials in the EU (ACT EU)
ACT EU is an initiative designed to transform the initiation, development, and running of clinical trials within the EU. This program builds on the EU-CTR and CTIS, aiming to further integrate clinical research into the European health system by promoting the development of high-quality, safe, and effective medicines. ACT EU has ten priority actions, including:
- Successful and timely implementation of the EU-CTR: Developing key performance indicators (KPIs) to track the performance of the European clinical trials environment and promoting larger, multinational trials, especially in academia.
- Implementing GCP modernization: Support to align the increasingly diverse range of clinical trial types and data sources.
- Developing key methodologies guidance: Ensure relevant EU expert groups pool their expertise and align priorities to accelerate future guidance development. Guidance is already available to support the planning and conducting of complex clinical trials, including the design of master protocols.
Tackling Cross-Border Clinical Trials
Facilitating cross-border clinical trials is one of the more complex issues within the EU. Many patients, especially those with rare or life-threatening diseases, find themselves looking beyond their home country for clinical trial options. However, the need for an EU-wide legal framework creates significant barriers.
Efforts to Overcome Cross-Border Trial Challenges:
- Focus on Patient Needs: Shifting from highlighting barriers to creating more options for patient participation in clinical trials across borders.
- Cross-Border-Focused Initiatives: EU-X-CT is a multi-stakeholder initiative to collect information on barriers to cross-border participation and develop recommendations for enabling better access. Initiatives supporting EU-X-CT include PCM4EU and PRIME-ROSE to facilitate cross-border participation in oncology trials.
Embracing Advanced Therapies
The expansion of new cell and gene therapies, particularly CAR-T and TCR cell therapies, is a notable trend in oncology. These therapies offer improved safety and high potency with fewer side effects than traditional treatments. However, they also bring unique regulatory challenges.
Navigating Advanced Therapy Medicinal Products (ATMPs) in the EU:
- Regulatory Challenges: The EU has an overall regulatory framework for ATMPs, Regulation (EC) No 1394/2007. Companies developing ATMPs must also be aware of specific and comprehensive guidelines for designing and conducting clinical trials, including legislation applicable to different process stages like GCP and Good Manufacturing Practice (GMP).
- Future Focus: Prepare for the next wave of developments, particularly therapies targeting solid tumors, such as tumor infiltrating lymphocytes (TILs). We recommend early engagement with the EMA Committee for Advanced Therapies (CAT). CAT plays a central role in the scientific assessment of ATMPs and can provide recommendations on classification and contribute to scientific advice.
Master Protocols and Adaptive Trial Designs
The increasing use of innovative trial designs like basket, umbrella, and platform trials is reshaping oncology research. These designs allow for evaluating multiple drugs or treatments simultaneously, offering a more flexible and efficient approach to drug development. As innovative trial designs have gained momentum, regulatory agencies have issued guidance to support developers, such as the EMA concept paper on platform trials.
Benefits of Adaptive Designs:
- Efficiency: Enabling simultaneous testing of multiple drugs against a standard control arm can significantly reduce time and resources.
- Flexibility: Adapting the trial as it progresses based on interim results or as the treatment landscape evolves throughout a study allows for more dynamic decision-making and can lead to faster drug approvals.
Conclusion
Navigating the regulatory landscape for oncology trials in the EU requires a deep understanding of the opportunities and challenges of the evolving frameworks and initiatives. The looming deadline for transitioning studies running under the CTD to the EU-CTR adds urgency to these challenges, making it crucial for stakeholders to act promptly to adapt to these changes. By seeking early advice and leveraging these insights, stakeholders can streamline their clinical trial processes, enhance patient outcomes, and ultimately bring innovative treatments to market more efficiently.
For those looking to delve deeper into these topics, engaging with regulatory experts can provide the tailored guidance and strategic planning needed to navigate this complex landscape successfully. Whether you are a part of a pharmaceutical company, a researcher, or a healthcare professional, understanding these dynamics is crucial for successfully executing oncology clinical trials in the EU
Partner with Worldwide Clinical Trials for comprehensive support and expert guidance in navigating this complex regulatory environment. Our team of agile regulatory experts is ready to assist you in adapting to these changes and optimizing your clinical trial strategy.
Contact us to learn how we can help you navigate these changes with precision and expertise.
