EU Clinical Trial Regulation: What you Need to Know

By Published On: February 1st, 2022Categories: Clinical Evaluation Reports - CER, Clinical trial, EU MDR


EU Clinical Trial Regulation: What you Need to Know


For manufacturers, clinical trials or at least the protocol are already planned and set to go for up to 2023. However, a new development in the clinical trials regulation means what you had done so far could very well need a drastic remake. The new changes outline the future scenario of European clinical research.


The European Medicines Agency has revealed that its long-awaited clinical trials portal and the database for clinical trials are undergoing re-design by the European Clinical Trials Commission.


On 31 January 2022, the European Union (EU) Clinical Trial Regulation 536/2014 (EU-CTR) will take effect, replacing EU-CTD. This new regulation will significantly change how clinical trials are conducted in the EU.


The goal behind introducing EU-CTR is to simplify and harmonize the clinical trial process in the EU by establishing a single set of rules for all EU member states to follow when implementing this regulation by 31 January 2022. The new regulation aims to overcome EU-CTD’s shortcomings by creating a single assessment process for multinational clinical trials across 28 EU member states. It also provides greater transparency by requiring public disclosure of certain information about clinical trials within six months of completion. The new regulation also allows patients to participate.


EU Clinical Trial Directive to Clinical Trials Regulation


EU Clinical Trial Directive to Clinical Trials Regulation


EU-CTD was established in 2001 and has been implemented through national legislation by its 28 member states. However, its real-life implementation created unexpected challenges for sponsors and others. For example, the directive has not always carried the same weight as regulation. Each EU member state had to implement its legal requirements through national legislation, creating a fragmented assessment process for multinational clinical trial applications and a complex data submission framework. It also meant that the public had limited access to clinical trial applications and results in the EU.


On April 16, 2014, the European Clinical Trials Regulation (CTR) was published in the Official Journal of the European Union. This new legislation replaces the existing Clinical Trials Directive 2001/20/EC. It is intended to improve transparency, efficiency and robustness of clinical trials for the benefit of patients and public health more generally. The CTR was active from 2014.


However, a key element of this CTR was missing up until now: the Clinical Trial Information System (CTIS). Finally, the centralised EU portal and database are live and ready to go after several years. This is considered a huge step forward as this is a people and patient-oriented decision expected to boost medical device manufacture and innovation.


What are the new additions to the EU Clinical Trials Regulation?


EU Clinical Trials Regulation


Even after the EU Clinical Trials Regulation update, the submission process of clinical trials in Europe remains unchanged for the most part. If a clinical trial has approval from a single ethics committee (EC) and competent authority (NCA), then the trial can proceed to be conducted in any EU member state. This is referred to as the Single Protocol approach. With EU-CTR, multinational applications will be assessed and reported by a single reporting member state throughout the trial’s life cycle. The reporting state will act as a central liaison between sponsors, other member states, and ethics committees or other agencies. According to the EU-CTR Article 5, the member states will have six days to review the application dossier from when they receive it to notify the sponsor and other member states.


The reporting member state has a tremendous responsibility on its shoulders. It is required to lead all centrally authorized clinical trials for that company across all countries in which that company conducts clinical trials. This includes submitting annual safety reports after each trial phase and annual reports summarising all trials.


The most notifiable change involves the clinical trial submission. In order to make the clinical trial experience more streamlined and user-friendly for EU sponsors, the EU Clinical Trials Regulation implemented a new portal and database called the Clinical Trial Information System (CTIS). CTIS enables a single, centralized electronic submission of data instead of having sponsors submit different dossiers to different authorities. All clinical trials will now be submitted in this database. So sponsors must upload and submit all data, including initial clinical trial application data and documentation, late amendments, literature through CTIS. A single submission is now required. However, trials that were approved before 31.01.23 were under EU-CTD. Those can still be accepted still 2025.


Another big change that grabbed everyone’s attention was the transparency rules. Protocols and other documents must be publicly disclosed throughout the development process, with few exceptions. Before EU-CTR, transparency was most often required when a product was ready for market approval.

How does it affect you?


How does it affect you


The first problem for manufacturers is that each protocol must be submitted to the relevant Member State’s CTIS (Clinical Trial Information System) before it can be used for recruitment purposes. Once a protocol has been submitted, it becomes publicly available on that country’s CTIS website. This means that a competitor can stay ahead of the curve, and any study wanting to follow your trial can go ahead of you.


However, it also means you have a better chance of collaboration and are privy to the knowledge of recent developments. Also, not all data is to be made public access. For example, some confidential information (such as trade secrets or personal information ) is protected under EU-CTR and is not required for full disclosure. So, there is very little reason to be alarmed.


How successfully adapt to the new changes?


How successfully adapt to the new changes


To ensure a smooth transition, here are some steps you can take:


  1. You will need to rethink your roles and responsibility. There will be a lot of new changes and small details to look for in the clinical trial, so you need to make sure every responsibility is assigned to the right person.
  2. Revamping your training program won’t hurt either. Your employees need to know about the new changes and how to work with them.
  3. Hire an expert to do the heavy lifting like literature review and protocol review if needed. It’s better to get it right the first time!
  4. You will need a stronger connection between your clinical and regulatory teams.
  5. Focusing on the importance of First Time Quality during your meetings with regulatory representatives will make sure you are ready.


The new EU clinical trial regulation changes are here to stay, and it’s focused on better and more advanced medical research. Manufacturers who adapt to this quickly will be the ones leading in the upcoming years in research and innovation.


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