Sponsors and clinical trial applicants must take into account the impact of EU CTR on their organisational infrastructure and study management practices, including regulatory affairs, clinical operations, training and more.
Here are five critical points to consider in preparation for EU CTR:
1. Conduct an EU CTR Readiness Exercise
The impact of EU CTR may vary depending on the size and status of an organisation's infrastructure, activities and portfolio. To assess your readiness, carry out an EU CTR preparedness investigation using a change management approach involving:
- A gap analysis to determine the extent and scope of changes needed
- Input from key department representatives, including clinical development, regulatory affairs, medical affairs, legal and others
- Technical solutions and training for staff as needed
Smaller organisations with fewer products and trials may experience minimal changes, while established organisations with larger portfolios may need to make more significant changes. Regardless of the size of the organisation, this exercise should be repeated regularly to keep pace with evolving EU CTR requirements.
2. Review Outsourcing Strategy and Vendor Management
Clinical trial start-up procedures, such as site selection and document collection, remain the same under EU CTR, but the way in which submissions are made via the Clinical Trial Information System (CTIS) introduces new responsibilities. Consider the following:
- Management and oversight of CTIS, including roles and responsibilities for CTIS users
- Transparency and protection of personal data and commercially confidential information
Once responsibilities have been agreed upon, vendor management teams should incorporate these into vendor selection and contract agreements.
3. Assess Study Operations
The EU CTR introduces an overhauled Clinical Trial Application (CTA) evaluation process and Clinical Trials Information System (CTIS) to support submission activities. It is imperative to prepare for the impact of these modifications on trial activities and submission and to train the relevant teams accordingly. Ensuring compliance with all new demands and responsibilities during a clinical trial cycle and documenting everything properly in the trial master file is of utmost importance.
With the implementation of the unique CTA gateway, there is a greater interdependence between submissions from individual countries. This must be considered when putting together the Part I and Part II applications and when organising the relevant clinical operations and start-up activities. The maintenance phase also comes with its own set of rules, including stricter modification submission guidelines, new notification forms, specific notification timelines and a quicker turnaround time for responses to information requests.
The maintenance rules during clinical trials have become more rigorous under the European Union Clinical Trials Regulation (EU CTR), which includes:
- Limiting the number of Part I modification assessments that can be submitted simultaneously
- Implementing new forms of notifications, such as third-country inspection reports
- Establishing specific timelines for planned and unplanned event notifications
- Reducing the response time for authorities’ or ethics committees' information requests to 12 calendar days
4. Review Clinical Trial Transparency
In order to comply with the heightened transparency requirements of EU CTR, sponsors must carefully handle Confidential Commercial Information (CCI) and Protected Personal Data (PPD) within their records. This might entail creating templates or offering guidance to medical writing teams. Furthermore, trial participants should have access to the layperson summary of trial results and full clinical study reports once the trial is finished.
Procedures for redaction must be established to safeguard information before uploading it online, and these procedures must be communicated to all trial management and oversight parties involved.
5. Evaluate Transition to EU Clinical Trials Regulation
The directive provides guidance for ongoing trials, giving sponsors the option to continue conducting their trials under the existing regulations until 30th January 2025. After then, all clinical trials for drugs under the jurisdiction of EU CTR, which includes interventional clinical trials for drugs conducted in EU/EEA nations, must either be finished or transitioned (with official decision in place) to EU CTR. This transition involves submitting the trial in CTIS, which confirms its transfer to the new framework upon approval, and may involve modifications to study records such as redactions. From that point forward, all obligations under EU CTR will be in effect, including those relating to transparency and reporting/publication.
The three-year timeframe for the transition, starting in 2022 and ending in 2025, offers ample opportunity for all parties to prepare for the significant changes ahead. The switch will necessitate a great deal of resources from both sponsors and Member States, in order to comply with the EU CTR rules. A thorough evaluation of the current trial portfolio is vital to identify which trials must transition and which may remain under the prior clinical trial directive. This also means that backers must operate two separate systems for quality management and reporting requirements/results posting, based on the regulatory arrangement for governing the trial.
Trials that are slated for transition must have their Part I documents, including the protocol, Investigator's Brochure and Investigational Medicinal Product Dossier, fully aligned before the shift can occur. This may necessitate considerable adjustments (substantial amendments to be submitted under CTD) before the transition can start, and the schedule for these evaluations must be taken into account. It is therefore important to perform a trial portfolio assessment promptly to identify any changes that must be made prior to mid-2024, allowing enough time for the actual transition to happen before January 2025. The transitions should be arranged from 2023 to 2025 but, to avoid overwhelming the system, it is suggested to minimise the number of transitions in the initial half of 2023 due to the expected increase of new CTAs on 31st January 2023.