The EU Clinical Trials Regulation After the Transition: The Three Dates, CTIS and What Comes Next

The three-year transition to the EU Clinical Trials Regulation ended on 31 January 2025. There is now a single route into clinical research in the European Union, a single public register of it, and no remaining path back to the old system. For sponsors who completed the move, the regime is settled. For any trial that did not transition in time, the position is worse than a missed deadline.

The three dates that define the regime

Regulation (EU) No 536/2014 is easier to understand as three steps than as one event:

• 31 January 2022 — entry into application. On this date the Regulation entered into application and repealed Clinical Trials Directive 2001/20/EC together with the national laws implementing it.
• 31 January 2023 — CTIS became mandatory for new applications. Until 30 January 2023 sponsors could choose between the Clinical Trials Information System and the Directive route. From 31 January 2023, every new clinical trial application had to go through CTIS.
• 31 January 2025 — end of the transition for ongoing trials. From this date, trials authorised under the Directive that were still running had to comply with the Regulation, and their sponsors had to have recorded information about them in CTIS.

The staged design is why confusion persists. A sponsor can correctly say the Regulation applied from 2022, that CTIS became compulsory in 2023, and that the switchover finished in 2025 — all three are true and they describe different obligations.

What happens to a trial that did not transition

This is the part worth being blunt about. A trial that missed the January 2025 deadline cannot be brought across retrospectively. Transfer applications are no longer possible, and the position cannot be adapted after the fact.

The route available is to submit a new application through CTIS — which is a materially different exercise from a transition, with the assessment and authorisation that implies. Competent authorities may also take corrective action in respect of trials that were not switched. A sponsor still running a Directive-era trial outside CTIS in late 2026 does not have an administrative backlog; it has a regulatory problem.

What the Regulation actually changed

The headline change is procedural. A sponsor submits one online application through CTIS for a trial running in several countries, instead of applying separately to each national competent authority and each ethics committee. For multinational trials that is the whole point of the reform.

Authority has not moved, though. Evaluation, authorisation and supervision remain the responsibility of Member States and EEA countries. What the Regulation gives them is a shared mechanism: they can evaluate and authorise applications together, process them collaboratively, request further information, and supervise authorised trials within CTIS. The single application does not mean a single decision-maker.

Alongside the harmonised assessment and supervision processes, the Regulation sets out to maintain high safety standards for participants and to improve information-sharing and collective decision-making, with the stated aim of making the EU more attractive for large-scale clinical research and easier for multinational trials.

One application, several authorities — what that means in practice

The distinction between a single application and a single decision is the one that most often surprises sponsors moving from a national-only footprint to a multinational one.

Because Member States retain evaluation, authorisation and supervision, a sponsor is still dealing with several regulators — they are simply doing it through one system and, where they choose to, in a coordinated way. Requests for further information can come from the assessment process rather than from a single named authority, and the sponsor has to be able to respond within the timetable the system imposes rather than negotiating bilaterally as was often possible under the Directive.

Two operational consequences follow. The first is that response capacity has to be real: a coordinated assessment compresses the window in which a sponsor must produce substantive answers, and a small regulatory team covering several trials can be overwhelmed by concurrent requests. The second is that internal sign-off has to be faster than the external clock. Organisations that built approval chains around the slower, sequential national process can find that their own governance, rather than the regulator, is the binding constraint on meeting a CTIS deadline.

The transparency dimension is the underappreciated one

CTIS includes a searchable public website, so anyone with an interest can access information on trials conducted in the EEA. That is a structural change in how clinical research is conducted in Europe, and it is frequently treated as a side effect rather than a design feature.

Two consequences follow for sponsors. First, what goes into CTIS is not simply a submission to a regulator — portions of it become public, which raises the standard for accuracy and for internal review before anything is filed. Second, the people preparing and approving those submissions need to understand which fields are published and which are not. That is a competence requirement sitting inside what looks like a data-entry task, and it is the same pattern now visible across regulated industries: a central database turns record quality into the face an organisation presents to every authority and to the public simultaneously. The device sector has just arrived at the same point with EUDAMED becoming mandatory.

How this sits with the new GCP

The Regulation governs the authorisation and oversight architecture. ICH E6(R3) governs how the trial is actually run, and it has been in effect since 23 July 2025 — six months after the CTR transition closed, with its Annex 2 following on 15 January 2027.

The two fit together in a way worth noting for anyone designing training. The CTR centralises the paperwork and the transparency; E6(R3) decentralises the training judgement, requiring trial-related training to correspond to what is necessary for a person’s delegated activities, and oversight to be proportionate to the importance of the data being collected. A sponsor that reads the CTR as a case for standardising everything and then applies that instinct to site training is working against the grain of the current GCP, as set out in our guide to ICH E6(R3) and training sized to the task.

Where the CTR meets pharmacovigilance

Clinical trial safety reporting and post-authorisation pharmacovigilance are separate systems, and the boundary between them is a common source of error in organisations that run both.

A marketing authorisation holder’s obligations run through the Qualified Person Responsible for Pharmacovigilance — a named, EU-resident individual available on a 24-hour basis, with duties and a documentary trail set out in our guide to the QPPV role. Trial safety reporting under the CTR is a distinct obligation on the sponsor. Where a company holds both roles, the handover between them needs to be deliberate rather than assumed, particularly as a product moves from trial to authorisation.

The practical position in late 2026

For most sponsors the CTR is now simply the operating environment, and the useful questions are maintenance questions rather than transition ones.

Is every ongoing trial recorded in CTIS, including those that transitioned late in the window? Are the people preparing submissions clear on which fields become public? Is there a named owner for CTIS user and role management, given that access control is how a shared European system stays accurate? And has site training been revisited against E6(R3) rather than left as it was written under the Directive-era approach?

That last point is the one most likely to have been missed. Many organisations spent 2023 and 2024 on the transition itself — a systems and submissions project — and then met a new GCP six months after finishing it. Training written for the old framework will still be in circulation at a lot of sites.

The surrounding quality expectations have moved in the same direction. Manufacturing training must have its effectiveness periodically assessed under EU GMP Chapter 2; records must be reviewable by people who can genuinely interrogate them, as set out in our guide to data integrity training and MHRA GxP expectations; and device manufacturers carry the obligation through a named Person Responsible for Regulatory Compliance. Across all of them the regulator is asking the same question: can the person doing this work actually do it, and can you show that.