What is the Clinical Trial Regulation?

Regulation (EU) no. 536/2014 on clinical trials on medicinal products for human use (the “Clinical Trial Regulation”) was published in May 2014. However, full implementation was dependent on the functionality of the Clinical Trial Information System (“CTIS”), a new centralised portal and database which was not fully operational until April 2021. The European Commission confirmed that the Clinical Trial Regulation will apply from 31 January 2022 and CTIS will also go-live on that date.

Previously, clinical trials were governed by Directive 2001/20/EC on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use (the “Clinical Trial Directive”) together with divergent transposing legislation and guidance at national level. From an Irish perspective, it is intended that the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 will be repealed. Publication of national legislation implementing the Clinical Trial Regulation is expected before the end of 2021.
The aim of the Clinical Trial Regulation is to create an environment that is favourable for conducting clinical trials with the highest standards of patient safety, to harmonise decision-making and to foster work sharing and collaboration between Member States.

Timelines and Transitional Period

A three year transitional period will apply from 31 January 2022 to allow for clinical trials authorised under the Clinical Trial Directive to move to the Clinical Trial Regulation.
From 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.
By 31 January 2025, all ongoing clinical trials must have transitioned to the Clinical Trial Regulation and migrated to CTIS.

New concepts introduced under the Clinical Trial Regulation

New concept Effect
Clinical Trial definition The Clinical Trial Regulation creates the wider concept of a “clinical study”. A “clinical trial” is defined as a category of clinical study. The Clinical Trial Regulation does not apply to a “non-interventional” study, which is defined as “a clinical study other than a clinical trial”.
The Clinical Trial Regulation also introduces the concept of a “low-intervention clinical trial” which is subject to a lighter regulatory regime and involves the use of investigational medicinal products which have already been granted a MA, are being used in accordance with the protocol and the additional diagnostic or monitoring procedures do not pose more than minimal additional risk or burden to the safety of the subjects compared to normal clinical practice in any Member State concerned.
Harmonisation of rules across all Member States There will be identical rules for conducting clinical trials throughout the EU and an increase in the efficiency of the approval process. This is particularly important in the context of multinational trials.
CTIS is a single entry point CTIS is a single entry point, meaning that the sponsor will submit a single set of clinical trial documents to multiple Member States (where applicable) through CTIS. Following authorisation, modifications, amendments and safety reporting will be submitted through CTIS.
A single authorisation procedure, divided in two parts There is a single authorisation procedure for all clinical trials, divided into two parts:

  • Part I involves a scientific assessment of the core clinical trial documentation. In Ireland, part I assessment will be undertaken by the Health Products Regulatory Authority (“HPRA”); and
  • Part II is assessed at national level and involves an ethical assessment of the country-specific and site-specific documents (by the National Research Ethics Committee (“NREC”)).

Following this staggered assessment, each Member State concerned will reach a single decision and will notify the sponsor through CTIS.

Transparency measures Under the Clinical Trial Directive, limited information on clinical trials was publicly available. The Clinical Trial Regulation aims to enhance transparency and requires all information stored in CTIS to be publicly available unless exempt under the Regulation. Exemptions include personal data, commercially confidential data, confidential communications between Member States and information about clinical trial applications that have not yet been approved. Timing on public access will depend on the type of document and category of clinical trial.
Supervision and controls Under the Clinical Trial Regulation, the European Commission will use the principle of Union Controls to monitor Member States in relation to whether clinical trials are being supervised in compliance with the Clinical Trial Regulation at national level. The European Commission’s reports will be publicly accessible on CTIS.
Enrolment of vulnerable groups The Clinical Trial Regulation requires that specific consideration be given to the assessment of the application for authorisation of clinical trials involving minors, pregnant or breastfeeding women, incapacitated persons or other groups or sub-groups specified in the protocol. Such groups and sub-groups may include, for example, persons in military service, persons deprived of liberty or persons in residential settings. Member States may introduce additional national measures.

For further information, please contact Colin Kavanagh or Bridget McGrath.