EU-Verordnung über klinische Prüfungen: Wichtiges Update für globale Sponsoren

Artikel in Englisch

Replacing the older Clinical Trials Directive (CTD), this regulation ushers in a unified and more rigorous framework for conducting clinical trials across all EU member states. As the January 31, 2025, deadline for full compliance approaches, it is crucial for sponsors, particularly those involved in multi-national trials, to be well-prepared for the significant changes that the CTR introduces. The transition to the CTR requires careful attention to new regulatory demands, including enhanced safety protocols, stricter data protection measures, and a heightened focus on transparency. This article explores the CTR's key features, the potential risks of non-compliance, and the essential steps to ensure a smooth transition, thereby safeguarding the integrity and continuity of your clinical trials.

Key regulatory changes associated with the transition to EUR CTR

Designed to enhance the protection of trial participants and improve the quality of clinical data, this regulation also introduced more stringent safety protocols, increased transparency through intensified reporting, stronger data protection, and the use of plain language in documentation.

Understanding the transition: From CTD to CTR

During the first year after the CTR’s implementation, sponsors could choose to submit new trial applications under either the CTD or the CTR. However, from January 31, 2023, all new trials were mandated to comply with the CTR. Importantly, any ongoing trials expected to continue beyond January 31, 2025, must also be transitioned to the CTR. Any impacted trial that is not CTR-compliant by then, will face severe consequences ranging from trial suspension to financial penalties, reputational damage, operational disruptions, and more.

As we approach the final stretch of the transition period, the assumption is that all impacted organisations are well into the transition process given the severity of the consequences for non-compliance.

While most organisations should be well advanced in this process, research indicates that many organisations are still struggling to adhere to the new mandate. Recent surveys, such as those conducted by the European Medicines Agency (EMA) in early 2023, highlight that a significant number of sponsors had not yet fully transitioned their trials to meet CTR requirements. The Pharmaceutical Research and Manufacturers of America (PhRMA) also reported in 2023 that 55% of global pharmaceutical companies had begun the transition but are struggling with documentation standardisation and the new safety reporting requirements. These findings align with industry reports showing that many organisations, especially those outside the EU, are struggling with the transition's complexities. The Clinical Trials Transformation Initiative (CTTI) survey also noted that nearly half of the surveyed organisations had only just begun the process of adapting their trials to the CTR.

This is particularly concerning given the time-intensive nature of achieving full compliance. For instance, the process of transitioning trials typically takes around three months, assuming all documentation and procedures are in order. However, for multi-national trials or those involving innovative therapies, the process can be even more complicated, requiring extensive review and standardisation of trial documentation, safety protocols, and data management systems. 

The impact of non-compliance

With just five months left until the non-negotiable January 31, 2025, deadline, time is running out. For those still in the process of transitioning, now is the time to take the necessary steps to ensure compliance and safeguard the future of clinical trials. The cost of inaction is too high to ignore.

Non-compliance with the EU Clinical Trials Regulation (CTR) can have severe and wide-ranging consequences, impacting not only sponsors but also all stakeholders involved in clinical trials. One of the most immediate and devastating effects of non-compliance is the risk of trial suspension or termination by regulatory authorities. Such actions can abruptly halt ongoing research, leading to significant delays in the development of new therapies. This not only disrupts the progress of trials but also poses serious risks to patients who rely on these trials for ongoing treatment. The interruption of treatment due to trial suspension can have profound implications for patient health and well-being.

In addition to the risk of trial suspension, non-compliance can lead to substantial financial penalties imposed by the EU. Beyond the financial impact, failing to meet CTR standards can tarnish an organisation’s reputation within the global research community. This reputational damage can make it increasingly difficult to attract participants for future trials and secure partnerships with other research entities.

Operational disruptions are another critical consequence of non-compliance. Organisations found to be non-compliant may face increased scrutiny, including audits and investigations, which can divert resources away from essential research activities. These disruptions can further delay trial progress and strain organisational capacity.

Approach to compliance

Becoming CTR compliant involves the critical task of reviewing and standardising all trial-related documents to meet the CTR’s uniform requirements. For multinational trials, this task is particularly complex, as documentation must be harmonised across different member states. Additionally, the Clinical Trials Information System (CTIS) must be utilised correctly to ensure accurate and complete submissions. Familiarity with this new system is vital to avoid delays and potential compliance issues. It is also imperative that trials submitted for CTR approval are compliant with current standards. While no validation occurs at the time of submission, penalties will be applied if trials are found to be non-compliant during the subsequent evaluation process.

Regardless of where your organisation currently stands, based on our experience supporting numerous implementations of CTR, the following steps can help you navigate this transition:  

• Compile a comprehensive portfolio of all ongoing and planned trials. This will provide a clear overview of which trials need to be transitioned to the CTR and help prioritise actions based on urgency and impact.
• Conduct a gap assessment of your current clinical trial processes and documentation against the CTR requirements. This includes identifying areas where your trials may not meet the new regulatory standards. A thorough gap analysis will highlight compliance shortfalls and pinpoint areas that require immediate attention and ensure that trials are following current standards.
• Review and standardise all trial-related documentation to ensure consistency across different member states. This is particularly critical for multinational trials where discrepancies in documentation can lead to delays or non-compliance.
• Ensure that your safety monitoring and data management systems are aligned with the CTR’s stricter requirements. This includes updating protocols for safety reporting, adverse event monitoring, and data transparency.
• Establish or strengthen communication with regulatory authorities to stay informed about any updates or changes in CTR implementation guidelines. Proactive engagement can also facilitate smoother approval processes and quicker resolution of compliance issues.
• Familiarise your team with the CTIS and ensure that all trial submissions are accurate and complete. Given the central role of CTIS in the CTR framework, understanding its functionalities and requirements is essential for compliance.
• Review your data handling practices ensuring compliance with the General Data Protection Regulation (GDPR), which is closely tied to the CTR. This step is crucial for safeguarding patient data and maintaining ethical standards in your trials.
• Sponsors should account for the time necessary to consolidate and standardise documents in multi-national trials, redact data, translate documents into plain language, and complete other complex procedures prior to submission. Time is also required to complete the Member State(s) evaluation procedure. To ensure expediency, the Member States have agreed on an expedited procedure for transitioning trials to the CTR, which will be applied whenever possible, as described in the CTCG Best Practice Guide. 
• Further considerations are variances in both country-specific and trial-specific requirements under the European Union Clinical Trials Regulation (EU-CTR). These requirements can vary significantly depending on the nature of the trial and the countries in which it is conducted. For example, each EU member state has its own National Competent Authority and ethics committee(s) responsible for the review and approval of clinical trials. While the EU-CTR aims to harmonise processes across member states, each country may have specific documentation, language, and procedural requirements that sponsors must fulfil. 
• Some countries may require that all documents, including informed consent forms and patient information sheets, be submitted in the local language. Some countries may have additional ethical considerations or require a separate ethics committee approval, even after a trial has been authorised at the EU level (MedTech Intelligence).
• Compliance with the General Data Protection Regulation (GDPR) is mandatory across all EU member states, but there might be additional national requirements regarding data storage, transfer, and patient consent.

How we can help

The transition to the CTR is not just a regulatory requirement; it is a fundamental shift that demands thorough preparation and execution, but navigating the complexities of the CTR requires specialised expertise. 

For those seeking further guidance on managing the transition and ensuring compliance, our Forvis Mazars team of compliance experts is equipped to assist you at every stage of the transition process, offering end-to-end services tailored to your specific needs whatever and wherever they may be.