Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use (the Clinical Trial Regulation) was published in 2014. The Clinical Trial Regulation introduced a new regime for EU clinical trials. It harmonises the rules for conducting clinical trials in the EU through a single clinical trial portal and database known as the Clinical Trials Information System (CTIS). The application of the Clinical Trial Regulation has been delayed several times as it requires the CTIS to be fully functional. The European Commission published a notice in the Official Journal of the European Union on 31 July 2021. The notice confirmed that the Clinical Trial Regulation is set to apply from 31 January 2022 and that the CTIS will go live on that date too.

Currently, clinical trials in Ireland are governed by the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations, 2004, SI No 190 of 2004 (2004 Regulations). These regulations transposed into Irish law the provisions of EU Council Directive 2001/20/EC (the Clinical Trial Directive). When the Clinical Trial Regulation is implemented on 31 January 2022, it will repeal the Clinical Trial Directive. It is intended that national legislation implementing the Clinical Trial Directive will also be repealed.

Key features of the Clinical Trial Regulation

Unlike the Clinical Trial Directive, the Clinical Trial Regulation will be directly applicable in all EU/EEA member states without the need for local transposition. This includes the 27 EU countries, Iceland, Liechtenstein and Norway. However, this does not include the UK, following Brexit. The Swiss Federal Office of Public Health (FOPH) has acknowledged on its website that these rules will affect clinical trials in Switzerland and that it is assessing the impact and closely monitoring further developments.

The Clinical Trial Regulation will ensure that rules for conducting clinical trials are harmonised throughout the EU/EEA. It will also allow a coordinated assessment of clinical trial applications between the Member States. Some areas of the Clinical Trial Regulation, such as language requirements and fees, will be governed by national laws.

The primary aim of the Clinical Trial Regulation is to ensure that “clinical trial data are reliable and robust while ensuring respect for the rights, safety, dignity and well-being of subjects”. It also aims to increase the transparency of clinical trial information with details on the authorisation and results of EU trials being among the information that is to be made publicly available.

Once implemented, the key features of the new Clinical Trial Regulation will include:

• Harmonisation across EU member states of the rules for conducting clinical trials

• Improved efficiency in the approval process for clinical trials

• Introduction of an authorisation procedure involving a single submission and approval of multinational clinical trial applications through a single entry point, consisting of an EU clinical trial portal and database (the CTIS)

• A harmonised procedure for assessment by Member States

• Strictly defined deadlines for assessment, and

• Involvement of ethics committees in the assessment procedure

Timeline and transitional period

Once the Clinical Trial Regulation is implemented, a three-year transition period will apply to allow for the move from the Clinical Trial Directive. There are four key timelines to bear in mind:

• 31 January 2022 to 31 January 2023 - All initial clinical trial applications can be submitted under either the Clinical Trial Directive or the Clinical Trial Regulation

• From 31 January 2023 - All initial clinical trial applications must be submitted under the Clinical Trial Regulation

• 31 January 2022 until the end of the transition period in 31 January 2025 - Ongoing clinical trials previously authorised under the Clinical Trial Directive can remain under the Directive, or they can transition to the Clinical Trial Regulation

• By 31 January 2025 all ongoing clinical trials must have transitioned to the Clinical Trial Regulation and migrated to CTIS

How can clinical trial sponsors prepare for the Clinical Trial Regulation?

The Health Products Regulatory Authority (the HPRA) has published a bullet point list of advice for sponsors of clinical trials to assist in the transition to the Clinical Trial Regulation. These include the following:

• Sponsors are encouraged to review their current clinical trial portfolios and identify the trials that they plan to submit under the Clinical Trial Regulation

• Sponsors should review their current portfolios to ensure that there are no outstanding submissions relating to the life cycle of any of their trials for example end of trial declarations or end of trial summary report

• Sponsors should consider how they plan to interact and manage their trials under the Clinical Trial Regulation and the associated CTIS, as both mark a significant departure from current processes

• CTIS interacts with various, existing EMA databases and systems. These include its Account Management portal known as IAM , its Organisation Management Service known as OMS and the Extended EudraVigilance Medicinal Product Dictionary (xEVMPD). The xEVMPDis a list of all medicinal products authorised and registered in the EU. Sponsors must ensure that the relevant data is registered in these databases prior to submitting an initial clinical trial application.

• The HPRA strongly recommends that both commercial and non-commercial/academic sponsors review the extensive and comprehensive training materials that are available from the EMA website and monitor both the EMA and HPRA websites for further updates

• Sponsors should also keep an eye on the HPRA website for the opening of registration for the upcoming HPRA Clinical Trial Regulation or ‘CTR’ information week, which is planned for November 2021.

Conclusion

Confirmation of the date of entry into application of the Clinical Trial Regulation and the ‘go live’ date for the CTIS are welcome developments. The Clinical Trial Regulation will introduce harmonised rules and increased transparency to the assessment and conduct of clinical trials in the EU. It will, however, result in significant changes to how clinical trials are assessed and conducted. Accordingly, relevant stakeholders are advised to familiarise themselves with the Clinical Trial Regulation and prepare for its application as soon as possible and not wait until the end of the transition period.

For more information contact a member of our Life Sciences team.

The content of this article is provided for information purposes only and does not constitute legal or other advice.