Role of EU Legal Representative under EU Clinical Trials Regulation

The EU Clinical Trials Regulation (CTR), effective from 31^st January 2022, has introduced a range of new requirements and procedures for clinical trial sponsors. The EU Clinical Trials Regulation (CTR) replaces the previous EU Clinical Trials Directive (CTD) and as of 31^st January 2025, all new and on-going trials must adhere to the updated legislation. One key change in the EU Clinical Trials Regulation (CTR) is the significantly expanded role of the EU legal representative. Unlike the previous Clinical Trials Directive, the CTR requires legal representatives to have a more active and comprehensive role in ensuring regulatory compliance. For sponsors planning to conduct trials in the EU, this means that careful selection of an EU-based legal representative is essential to meet the rigorous requirements of the CTR.

Which Sponsors Need an EU Legal Representative?

Sponsors who are not established in the EU must appoint an EU-based legal representative if they wish to conduct their clinical trial in the EU. This is not a new requirement, but one which was already in place under the previous EU Clinical Trials Directive (CTD). The EU Legal Representative is required in order to ensure that, should any enforcement action or legal proceedings be undertaken by any EU member state in relation to the trial, the overseas sponsor can be contacted and appropriately sanctioned under EU law as necessary.

The Changing Role of the EU Legal Representative

Under the previous EU Clinical Trials Directive (CTD), the role of the sponsor’s EU legal representative was not clearly defined. This meant that many companies offering legal representative services were largely providing a “post box” or “tick box” service for sponsors, which met the legislative requirement, but meant they were rarely actively involved in the conduct of the trial. In contrast, the Clinical Trials Regulation (CTR) clearly defines the role of the legal representative stating that the legal representative is responsible for ensuring the sponsor’s compliance with the CTR, and that all communication addressed to the legal representative shall be deemed as communication to sponsor. This means that the role of legal representative under the Clinical Trials Regulation (CTR) carries similar liabilities to those of the sponsor. In addition, the CTR stipulates that all trials must be conducted in line with Good Clinical Practice (GCP). As such, companies offering legal representative services are obliged to have a clear understanding of the principles of GCP, as well as the requirements of the Clinical Trials Regulation (CTR), in order to maintain effective oversight of trial conduct and ensure the sponsor complies with all applicable legislative requirements. Consequently, the “post box” or “tick box” service will no longer suffice and could even be potentially damaging both to the sponsor and their legal representative as outlined in more detail below.

Main Changes Resulting From the Introduction of the EU Clinical Trials Regulation (CTR)

It’s a common misconception that the EU Clinical Trials Regulation has simplified the process of applying for, and maintaining, clinical trial authorisations in the EU. In reality, the regulation introduces significant changes that have increased the complexity of managing EU clinical trials.

These changes have elevated the risks of delays, non-compliance and inadvertent disclosure of confidential information.

Here is a closer look at the most notable changes and what they mean for sponsors:

Harmonised Submission and Assessment via CTIS

Submission, assessment and regulatory authority oversight of trials conducted in the EU is now harmonised and managed via the clinical trials information system (CTIS). Whilst the submission of a single dossier to the Ethics Committees and Regulatory Authorities via CTIS has largely been welcomed by sponsors, there are many intricacies and hidden pitfalls linked to the use of this system which can often prove challenging to navigate requiring heightened vigilance, strategic thinking and forward planning. With regards to CTIS, technical difficulties can arise in due to it gathering information from a network of separate, standalone EU databases and portals. This relationship means that an issue in a linked database can result in issues in CTIS, and often requires expert knowledge of the system’s interactions to identify and resolve the root cause. With regards to assessment, sponsors can face challenges when managing assessment queries during the application review. Although Part I assessment is centralised for all member states concerned (MSC), Part II assessments are still handled separately by each MSC. There is a prolonged timeframe during which queries can be received, and no strict order as to which are received first i.e. Part I queries could be received after the responses to Part II queries have already been submitted. This can cause issues when, for example, Part I queries impact documentation submitted in Part II. Furthermore, despite overall harmonisation of the requirements, many national requirements still differ in specific parts of the application dossier which adds further complexity.

Increased Transparency and Risk of Data Disclosure

The CTR introduces the requirement for greater transparency of EU clinical trials to facilitate information and knowledge sharing amongst patient and scientific communities. This does however mean that sponsors must exercise great caution in managing submissions made via the clinical trials information system (CTIS) to prevent accidental publication of either confidential personal data leading to a violation of the EU’s general data protection laws (GDPR), or confidential commercial information which could in some cases impact patent filing strategy. To find out more about the relationship between CTR transparency requirements and patent filing strategy, please refer to our recently published whitepaper.

Changes to Timelines and Notification Requirements

There have been changes to the assessment and query response timelines for clinical trial applications, the classification of amendments and submission procedures, and there are increased requirements for the notification of trial milestones. Failure to appropriately plan for these changes could lead to invalidation of submissions, lapsed applications or non-compliance with the regulation. In the worst case scenario, these issues can damage the reputation of the sponsor and jeopardise the clinical trial progress.

Revised Requirements for Results Posting

Another significant change under the EU Clinical Trial Regulation (CTR) involves how clinical trial results are posted. Sponsors can no longer rely on simply uploading a Clinical Study Report (CSR) to meet their obligations. Instead, they must create and submit via CTIS both a standalone EU summary of results and a laypersons summary of results. The full CSR is only required to be uploaded to CTIS if the trial results are used in an EU Marketing Authorisation (MA) procedure, even if the MA is subsequently withdrawn. This shift requires careful planning and foresight to ensure that all documents are prepared and submitted on time. Failure to do so can lead to non-compliance with the CTR.

Having an EU legal representative who fully understands the revised requirements and procedures introduced by the clinical trials regulation (CTR) is critical to ensure sponsors maintain compliance with the legislation.

Who is Ultimately Liable for the Conduct of a Clinical Trial under the EU CTR?

With the numerous changes the CTR brings, and the requirements contained therein, it is worth considering the question: “Who is ultimately liable for the conduct of the trial?”. Under the previous EU Clinical Trials Directive the overall civil and criminal liability for the clinical trial lay with the sponsor and the investigator whereas under the EU Clinical Trials Regulation (CTR), in addition to the liability of the sponsor and Investigator, liability also lies with other parties to whom the sponsor has delegated tasks. This means that the EU legal representative could also be sanctioned under EU law if they have failed to meet their legislative requirement of ensuring that the sponsor complies with the EU Clinical Trial Regulation (CTR).

How DLRC Can Support Clients

DLRC can support clients who are sponsors of EU clinical trials, but are not established in the EU, by offering EU legal representative services. As part of the legal representative services offered by DLRC, clients have access to an independent, trusted partner and advisor, well versed in the new and existing requirements, who can provide support throughout the entire duration of the clinical trial.

To ensure regulatory compliance, DLRC can offer:

Effective oversight of clinical trials throughout the trial duration from initial submission through to the end of trial phase
Support with understanding the requirements of the CTR
Support with successful execution of submissions via CTIS
Strategic solutions to a variety of challenges that can be encountered during the course of a clinical trial
Access to a wider pool of experienced regulatory consultants who can provide a vast range of regulatory support, should the need arise.

Having DLRC as the EU legal representative service provider assists clients in maintaining compliance with the regulations throughout their clinical trial, ultimately effecting a smoother transition through the EU Marketing Authorisation Application (MAA) process which triggers a retrospective good clinical practice (GCP) inspection of the supporting trial(s).

Summary

Taken together, the changes in the EU clinical trials legislation have brought along many challenges and have placed increased obligations on sponsors, as well as increased responsibility on legal representatives to ensure adherence to the CTR and other applicable legislation such as Good Clinical Practice (GCP) and General Data Protection (GDPR). As a result of the increased liability placed on EU legal representatives, and the change in the role and responsibility of this entity, the procedures undertaken by the legal representative must change with it. Moving from a ‘post box’ type role, to one which ensures consistent and effective oversight of the entire trial is critical to ensure compliance with the CTR. It is therefore key, for clinical trials sponsors who not established in the EU, to select the most appropriately qualified entity to act as the EU legal representative for their trial. The knowledge and experience within DLRC, coupled with the processes established as part of the legal representative service, position us as a competent and trusted partner for our clients.

Find out how DLRC can maximise your company and products, empowering you to navigate the regulatory landscape with confidence. Email their award-winning team at hello@dlrcgroup.com, or use the link below.