New Clinical Trial Regulation 

Clinical trials in Ireland are currently governed by the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations, 2004, SI No 190 of 2004.

The Regulations transposed into Irish law the provisions of Council Directive 2001/20/EC.

new Clinical Trial Regulation (EU) No 536/2014 was adopted on 16 April 2014, and implementation is planned to take place in 2022. When implemented, Directive 2001/20/EC and associated laws will be repealed.

The following tabs aim to provide stakeholders with further information regarding the upcoming Clinical Trial Regulation. For further information, please contact ctreg@hpra.ie.


Key features of the new Clinical Trial Regulation 

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

  • Identical rules for conducting clinical trials throughout the European Union (EU);

  • Increase in the efficiency in approval process for clinical trials;

  • Single submission and approval of multinational clinical trial applications through an EU ‘Clinical Trial portal and database’ (known as the Clinical Trial Information System (CTIS);

  • A harmonised procedure for assessment by member states, divided in two parts;

  • Strictly defined deadlines for assessment;

  • Involvement of the ethics committees in the assessment procedure. 

The above will assist the Clinical Trial Regulation in achieving its aim of creating a favourable environment for conducting trials in the EU while also ensuring that the highest standards of safety for participants are maintained. The Clinical Trial Regulation also aims to increase the transparency of clinical trial information with details on the authorisation and results of EU trials among the information to be made publicly available. 

Timeline and transition to the new Regulation

Key dates for the implementation of the Clinical Trial Regulation
Please click on the image to view in full size. 

On 31 July the European Commission published its decision, via the Official Journal of the European Union, that the EU portal and EU database had achieved full functionality. The six month countdown for the go-live of the Clinical Trial Information System (CTIS) and the application of the Clinical Trial Regulation (Regulation (EU) No 536/2014) has now commenced and the go-live date has been confirmed as the 31 January 2022. Once the Clinical Trial Regulation is implemented a three year transition period will apply to allow for the move from the current European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations, SI No 190 of 2004 which transposed into law the provision of Council Directive 2001/20/EC. The transition period sets out the following key timelines:  

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

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

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

  • By 31 January 2025 all ongoing clinical trials will be required to have transitioned to the Clinical Trial Regulation and will need to be migrated to CTIS.

Sponsors should also be aware that the Voluntary Harmonisation Procedure (VHP) is due to end in advance of the Clinical Trial Regulation being implemented. The last day for all VHP submissions has been confirmed as 15 October 2021. Please see further information about the conclusion of the VHP procedure

Additional information in relation to the transition period and eligibility of clinical trials can be found on the Heads of Medicines Agency (HMA), Clinical Trials Facilitation and coordination Group (CTFG) Best Practice Guide for sponsors of multinational clinical trials.

HPRA and preparing for the Regulation 

The HPRA is working with the following partners to prepare for the implementation of the Clinical Trial Regulation: European Commission’s Expert Group on Clinical Trials (CTEG), the European Medicines Agency (EMA), the Heads of Medicines Agencies Clinical Trials Facilitation and co-ordination Group (CTFG), the Department of Health and the Irish Pharmaceutical Healthcare Association (IPHA).

The HPRA is also working closely with the newly established National Office for Research Ethics Committees (NREC) on a harmonised, national approach in advance of the introduction of the Clinical Trial Regulation and the accompanying Clinical Trial Information System (CTIS). In support of this goal the NREC and the HPRA have launched the Clinical Trial Regulation-National Collaboration Project — please visit our Clinical Trials webpage for more information. 

In addition to the above, the HPRA contributes to the development of the International Council for Harmonisation (ICH) guidelines through the Expert Group on Clinical Trials and CTFG groups.

Further information on these working groups is available on the following websites:

Guidance and documents

The following guidance and documents may be of assistance to stakeholders in further understanding and preparing for the implementation of the Clinical Trial Regulation:

  • The European Medicines Agency has released a Clinical Trial Information System (CTIS) – Sponsor Handbook which aims to provide clinical trial sponsors with the information required in preparation for using CTIS. The handbook will be updated as more information becomes available and sponsors are encouraged to check that they are referencing the most up-to-date version at the time. The EMA also welcomes feedback on the CTIS Sponsor Handbook and any proposals or comments can be submitted directly to the EMA via this feedback form.

  • The European Commission has released a set of documents that will be applicable to clinical trials once the Clinical Trial Regulation is implemented.

  • Further information on the upcoming Clinical Trial Regulation can also be located in the European Commission Question and Answer document.

  • EC-DG Sante/HMA-CTFG/EMA joint training on the Clinical Trials Regulation (EU) 536/2014: On 9 and 10 March 2021, to support Member States (MSs) in preparation for the launch of the Clinical Trial Regulation DG Sante of the European Commission, the European Medicines Agency and the Clinical Trials Facilitation and coordination Group of Heads of Medicines Agency organised a two day training event. Members of the competent authorities and the ethics committees from the various MSs attended. The two day training aimed to provide an overview of key changes proposed under the incoming Clinical Trial Regulation and included presentations on a number of different topics.

  • Guidance and data fields required to be completed by sponsors in the submission and management of a clinical trial in CTIS are available on the EMA website. 

 

Clinical Trial Information System (CTIS)

The introduction of the Clinical Trial Regulation will also see the introduction of the new Clinical Trial Information System (CTIS). This will act as a single entry point for submitting clinical trial information in the European Union (EU) and will support the daily business processes of Member States and sponsors throughout the life cycle of a trial. Additionally, CTIS will also assist in making clinical trial information in Europe more accessible and transparent. To support stakeholders ahead of the introduction of the Clinical Trial Regulation, and the launch of CTIS, the following European Medicines Agency (EMA) led training may be of assistance:

Clinical Trials Information System (CTIS): Virtual Information Day

26 October 2021: Among the topics for discussion at this webinar are a high level understanding of CTIS including a live demonstration of the restricted workspaces. More information on this webinar, including how to register, can be found on the EMA's information day webpage.

Clinical Trials Information System (CTIS) webinar: How sponsor organisations can prepare for CTIS

29 July 2021: This webinar is open to all sponsor organisations and topics covered include how sponsors can best utilise the relevant EMA CTIS training materials. Further information regarding this webinar can be located on the EMA's webpage for the webinar

EMA CTIS Training Programme Page

The EMA has also setup a dedicated CTIS training programme page, which will be updated throughout 2021 and stakeholders are encouraged to monitor this for the most up to date information. Training materials for clinical trial sponsors are available on topics such as an ‘Introduction to CTIS’, ‘Common Functionalities for all registered users’, ‘Authority workspace’ and ‘Sponsor workspace’.

An EMA-organised CTIS webinar on the ‘dynamic demo of sponsor workspace’ was held in September 2020. 

Further information regarding CTIS training events can be located on the CTIS highlights page.

Additional Information

The EMA has published CTIS user personas to aid organisations and individuals who will interact with CTIS. The personas outline who will action what as well as demonstrating the possible CTIS user roles that each persona may be given to allow them to perform their tasks.
 

The first version of the Principles for Sponsor organisation modelling for CTIS has been released by the EMA. The document aims to further assist sponsors in their preparations for CTIS and provides information as well as examples of organisation models.

The introduction of the new Clinical Trial Regulation will also herald changes to the safety reporting for clinical trials and will introduce new Annual Safety Report (ASR) process in CTIS. To provide further information on this the EMA are contributing to a Eudravigilance and Signal Management Virtual Information Day on 24 November 2021. 
 
In addition to the above, the EMA is setting up a network of master trainers for sponsors in pharmaceutical companies and contract research organisations (CROs)-further information regarding this can be located on the EMAs dedicated Clinical Trial Regulation homepage. Members of the various EU Member State competent authorities and ethics committees are also undergoing master training with the EMA.


Note: Please be advised that the EMA have launched a survey to collect expressions of interest from clinical trial sponsors for access to the CTIS testing site, also known as the CTIS Sandbox. The closing date for applications is 31 October 2021 with successful applicants being granted access in the third wave of the rollout of the training environment the date for which has yet to be confirmed. Interested parties should visit the EU Survey Website to register their interest.

What can sponsors do now?

The HPRA has the following advice:

  1. Sponsors are encouraged to review their current clinical trial portfolios and identify the trials that they plan to submit under the Regulation. In preparation for submitting under the Regulation the HPRA, in tandem with the NREC, has launched the Clinical Trials Regulation-National Collaboration Project (CTR-NCP). Interested sponsors can read more about how to get involved with this in the Guide to Clinical Trials Regulation-National Collaboration Project

  2. Sponsors should review their current portfolios to ensure that there are no outstanding submissions relating to the life cycle of any of their trials e.g. end of trial declarations or end of trial summary report.

  3. Sponsors of VHP trials should review any upcoming substantial amendments to determine if these can be submitted in advance of the end of the VHP procedure (the last submission date is the 15 October 2021) to avoid them being assessed individually by the various Member States in the period before the commencement of the CTR. 

  4. Sponsors should give consideration to how they plan to interact and manage their trials under the CTR and the associated CTIS as both mark a significant departure from current processes.

  5. It is strongly recommended 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.

  6. Sponsors should also keep an eye on the HPRA website for the opening of registration for the upcoming HPRA CTR information week planned for November 2021. 

  7. CTIS interacts with various EMA existing databases and systems such as IAM (register users), OMS (search for organisations) and xEVMPD (search medicinal products). Sponsors must ensure that the relevant data is registered in these databases prior to submitting an initial clinical trial application. Sponsors who are unsure of their OMS registration status can review this on the EMA’s Substance, product, organisation and referential portal.

  8.  An EMA account is required to access the CTIS restricted workspace and users of other EMA applications (e.g. EudraVigilance) can use these log in details to access this. Information specific to registering a Sponsor administrator can be located in the EMA CTIS online modular training programme with particular reference to module 3 and 19 and the accompanying step-by-step guides and video tutorials as well as the latest issue of the EMA CTIS Highlights newsletter. Registration for high-level CTIS administrators is open as of September 2021.

  9. When considering user registration in CTIS organisations should also give some thought as to whether they wish to assume an Organisation-Centric or CT-Centric approach and more information regarding this can be located in module 7 of the EMA CTIS online modular training programme.  

SME and academia

A specific Clinical Trials Information System (CTIS) training module for SMEs and Academia has been produced by the EMA and can be found on the CTIS online modular training programme page of the EMA website under module 19. SME and Academia are strongly encouraged to consult the module which covers important aspects such as user access management and how to create, submit and withdraw a clinical trial application.

Webinar for small and medium-sized enterprises (SMEs) and academia on the Clinical Trials Regulation and the Clinical Trials Information System (CTIS)

An EMA webinar for small and medium-sized enterprises (SMEs) and academia on the Clinical Trials Regulation (CTR) and the CTIS is planned for the 29 November 2021. The webinar will include an overview of the CTR, an introduction to the new process for submitting clinical trials as well as the functionality of CTIS. More information regarding the webinar can be located on the event information page.

Dedicated training webinars detailing essential information on CTIS for micro, small and medium-sized enterprises (SMEs) and non-commercial (academic) sponsors

The first training session, held on the 22 February 2021, provided an overview of CTIS, user access management (including how to register users), sponsor user management and sponsor roles and permissions in CTIS. Further information can be found on the EMA's webpage for Day 1 of the webinar.

The second training session, held on the 4 March 2021, covered submitting an initial trial application in CTIS, updating an initial trial application and making substantial modifications along with adding a concerned Member State, making non-substantial modifications and submitting trial results. For more information please see the EMA's webpage for Day 2 of the webinar.

Webinars – November 2021

The new Clinical Trial Regulation explained

The Clinical Trial Regulation (Regulation No 536/2014) will come into effect on 31 January 2022. The HPRA, in conjunction with the National Office for Research Ethics Committees, held a series of one–hour webinars from Monday 22 to Thursday 25 November to help stakeholders understand the new requirements. 

The webinars covered topics such as an overview of the Regulation, including post-authorisation and compliance aspects, and guidance on next steps for sponsors and investigators. The Department of Health provided an update on the national framework for the Regulation. 

The aim of the webinars was to present the main changes that those involved in clinical trials in Ireland can expect when the Regulation is implemented, and throughout the three-year transition period that will follow.   

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Monday 22 November: General principles and new concepts

The following presentations are included in the video below: 

These presentations can be downloaded by clicking on the titles above. 

 

Tuesday 23 November: Post-authorisation, transition and how can I prepare?

The following presentations are included in the video below: 

These presentations can be downloaded by clicking on the titles above. 

 

Wednesday 24 November: Ireland - how will we implement?

The following presentations are included in the video below: 

These presentations can be downloaded by clicking on the titles above.

 

Thursday 25 November: Ireland - Compliance aspects

The following presentations are included in the video below: 

These presentations can be downloaded by clicking on the titles above.