The EU Biotech Act could rewrite clinical trial regulation. Is CTIS ready?

Why the Biotech Act is a CTIS story

The European Biotech Act is usually discussed as a competitiveness initiative. For regulatory affairs and clinical operations teams, one of its most consequential effects is less glamorous: the Clinical Trials Information System (CTIS) will have to be substantially rebuilt.

On 1 October 2026, EMA reported that its Management Board had been told the proposed changes to the authorisation and supervision of clinical trials 'impact approximately 70% of the current CTIS functionality'. All clinical-trial functionality foreseen by the Biotech Act is planned to be delivered in a new, modern CTIS platform, with work starting in early 2027. A detailed roadmap, including resource impact, goes to the Board in December 2026. EMA also notes that, on the ambitious timeframe set for the legislative procedure, the first changes to the Clinical Trials Regulation could come into force in early 2028.

CTIS is not a niche system. EMA says it has supported the authorisation and management of more than 14,000 clinical trials since its launch in 2022, with more than 200 new clinical trial applications a month.

Europe wants to simplify clinical trials. Doing so means rebuilding much of the infrastructure trials currently run on, while the rules it has to implement are still being negotiated.

What does the Biotech Act propose for clinical trials?

The Commission adopted the proposal on 16 December 2025 as COM(2025) 1022, procedure 2025/0406(COD). It is a Regulation 'on establishing a framework of measures for strengthening Union's biotechnology and biomanufacturing sectors particularly in the area of health', and Article 58 amends the Clinical Trials Regulation, Regulation (EU) No 536/2014. The Commission's case is blunt: the share of commercially sponsored clinical trials run in the European Economic Area fell from 22% in 2013 to 12% in 2023, and validated multinational applications take on average 113 days in the EU, against 60 days in most comparable regions.

The clinical-trial measures in the proposal, as the Commission summarises them:

EMA's own summary uses slightly different words — 'major modifications', 'common medicinal product dossiers' — for what the legal text calls substantial modifications and the investigational medicinal product core dossier. We use the legal terms below.

What does '70% of CTIS functionality' actually mean?

It does not mean CTIS is 70% wrong. It means the proposed operating model differs enough from the 2014 Regulation that most of what the system does today — the timers, the workflows between reporting and concerned Member States, the modification process, the dossier structure — would have to change or be added to.

The Commission's own financial statement for the proposal describes it in the same terms: 'multiple new workflows, parallel submissions, amended dossier requirement, a core product dossier and extension to combined studies including in-vitro diagnostics'. It asks for additional EMA staff to design, test and train sponsors and Member States on new CTIS functionalities and modules.

For sponsors, 70% of the system changing is the practical measure of the reform. Every one of those functions sits behind an SOP, a submission template, a training course and a habit.

Can you build a system while the requirements are still moving?

This is the real tension. The legislation is not final, and EMA is already planning its implementation.

EMA's answer is two tracks. The current platform 'will need immediate investment' so that key functions, starting with the accelerated assessment timelines, are available as early as possible and in time for adoption. Everything else goes into the new platform.

That is a sensible plan. It also means sponsors may see two system changes, not one: shorter timers on today's CTIS first, then a new platform.

And the requirements are moving. According to Sidley's analysis of the Parliament draft report, the rapporteurs propose moving the Part I scientific and ethical assessment of multinational trials to a new EU Clinical Trials Expert Committee, shortening Part I and Part II phases further, and adding a voluntary EMA-administered opt-in pathway. Whether any of that survives, it would change the CTIS workflow more than any of the timelines in the Commission's text. EMA cannot finish specifying a system whose central assessment step may still move from Member States to an EU committee.

Fixed dates instead of a functionality audit

The 2014 Clinical Trials Regulation learned this lesson the hard way. Article 99 made it apply six months after the Commission published a notice confirming the EU portal and database were fully functional. The Regulation was adopted in 2014 and applied from 31 January 2022, because the system took that long.

The Biotech Act proposal takes the opposite approach. Under its Article 67(3), most of the Clinical Trials Regulation amendments, including the new timelines and the core dossier, would apply six months after entry into force. The new chapter with the accelerated procedure for health threats and combined studies, and the changes to Article 28, would apply after nine months. A new Article 98a of the Clinical Trials Regulation would require EMA to submit a revised development plan for the EU portal and database to its Management Board one month after entry into force, and that plan 'shall ensure that all required system functionalities are available by the date of application'.

Our view: fixed dates are the right choice for a reform whose purpose is speed. A 2014-style audit gate would have pushed the new rules out by years. But a fixed date shifts the risk. If a function is not ready when the law applies, the obligation still exists. Sponsors and Member States would then be applying new rules through workarounds, with guidance catching up.

The core dossier could be a bigger deal than it sounds

Today, the same investigational medicinal product information is submitted and assessed again in each trial that uses it. The proposal adds a new Chapter IVa to the Clinical Trials Regulation, Articles 27a to 27c, that changes the unit of assessment.

• Establishment: with a clinical trial application, the sponsor may request a core dossier through the EU portal. The reporting Member State of that first trial becomes the depositary Member State and checks completeness and suitability.
• Reuse: once established, the core dossier is referred to in every later application for that trial and in every 'corresponding clinical trial' of the same product. The other Member States rely on the depositary's assessment and must not duplicate it.
• Maintenance: the sponsor keeps the core dossier up to date, reviews it at least once a year and requests changes through the depositary Member State.
• New trials: the reporting Member State of a new trial assesses, with the depositary, whether the core dossier — including the investigator's brochure and IMPD — is adequate for that trial, and can require it to be changed.
• Ongoing trials: the sponsor assesses whether a core dossier change makes a substantial modification necessary in the corresponding trials already running (Article 27b(6)).

The proposal answers more of the obvious questions than most commentary suggests: who owns it, who assesses it, how often it is reviewed. What it leaves to Commission implementing acts under Article 27c is the procedure, the cooperation between Member States and how the depositary role can change. And it puts the hardest question on the sponsor: when the core dossier moves to a new version, which of the trials referencing it need a substantial modification, in which Member States?

Parallel substantial modifications need better change-impact control

Today a sponsor generally waits for one substantial modification to be decided before submitting the next to the same trial. The proposal defines a 'parallel substantial modification' as one submitted before the decision on a previous one is notified, allowed where it concerns 'distinct and independent aspects of the dossier'. The recitals present it as a way to respond faster to safety updates, new science and operational changes.

That is genuine flexibility. It also means a trial can have two open versions of its dossier at the same time, possibly in different states in different Member States. Before every submission, someone has to answer:

1. Which aspects of the dossier does this change touch, in Part I and Part II?
2. Do those overlap with a modification still under assessment?
3. Which Member States, documents and core dossier elements are affected?
4. Which version of each document is currently approved, and where?
5. What happens to this change if the earlier one is refused or conditioned?

As procedures become more flexible, keeping the regulatory state of a trial coherent becomes more important, not less. 'Distinct and independent' is a claim the sponsor makes and the Member State checks. It is only as good as the sponsor's map of what depends on what.

Combined studies: one application, or one interface?

A trial of a medicine that depends on a companion diagnostic or a device can today fall under three frameworks — the Clinical Trials Regulation, the Medical Devices Regulation (EU) 2017/745 and the IVD Regulation (EU) 2017/746 — with separate applications, authorities and timelines. The Commission's recital says the complexity comes from applying the requirements of 'two or three Union legislative frameworks', usually across several Member States.

Proposed Article 14c allows a single application for a combined study, submitted through the EU portal, assessed in a coordinated procedure led by a reporting Member State, covering both competent authorities and ethics committees, and ending in a single decision per Member State. A positive conclusion of the reporting Member State is deemed to be the conclusion of all Member States concerned, with narrow grounds for disagreement.

The open question is how integrated the assessment really becomes. Article 14c leaves the streamlined procedure, safety reporting during the study, sponsor responsibilities, supervision and the functionalities of the EU portal and database to a Commission delegated act. Until that exists, the risk is a combined front door with three regulatory frameworks behind it, each with its own requirements, still assessed by different experts.

Will an integrated submission create an integrated assessment, or put several regulatory frameworks behind one interface? The answer is in the delegated act, not the Regulation.

Faster does not automatically mean simpler

Shorter statutory timelines are an outcome, not a process design. The policy aim is clear and right: make Europe a more attractive place to run trials. But what decides whether sponsors feel the difference is less visible:

• Predictable requirements, settled before systems are built.
• Clear transition rules for trials that started under the old procedure.
• System availability on the date the law applies.
• Updated guidance, Q&As and harmonised templates.
• Training for sponsor, CRO and Member State users.
• SOP and template changes across every company running EU trials.
• Ethics committees and national authorities able to meet the shorter clocks.

The transition rule is already worth reading. Under the proposed amendment to Article 98(1), the Clinical Trials Regulation as it stood the day before the new rules apply continues to govern authorisation, substantial modification and addition of a Member State for trials whose authorisation request was submitted before that date. Read with Article 67(3), that would mean long-running trials stay on the old procedures while new ones use the new procedures, both in CTIS, potentially for years.

A month saved on assessment is worth little if sponsors spend it resolving which rulebook, which template and which system version applies to which trial. That is not a prediction. It is the risk the implementation has to avoid.

What is confirmed and what is not?

Status as of 6 October 2026:

Do not turn a regulatory proposal into a regulatory requirement. Nothing in this article applies to a clinical trial today.

What clinical regulatory teams should watch in 2026–2027

None of this justifies rewriting SOPs yet. It does justify knowing what to watch, and starting the inventory work that will be needed anyway.

1. Parliament's committee vote, expected in December 2026, and whether the EU Clinical Trials Expert Committee proposal survives.
2. EMA's CTIS roadmap to the Management Board in December 2026, and the public summary of milestones.
3. The Council position, possible in the first half of 2027, and the trilogue outcome.
4. The final definition and procedure of the investigational medicinal product core dossier, and the implementing acts under Article 27c.
5. The final rules for parallel substantial modifications.
6. The minimal-intervention and low-intervention categories, and how trials are classified into them.
7. The combined-study procedure and its delegated act.
8. The transition rules for ongoing trials, and how CTIS will run both regimes.
9. Training, user-access and data-migration plans for sponsors.
10. Member State and ethics committee readiness for the shorter timelines.
11. Effective dates in the published text compared with CTIS technical availability.
12. Your own portfolio: which products are in several EU trials and could use a core dossier, and which trials combine a medicine with a device or IVD.

Our view: simplification creates a transition-management problem

The Biotech Act's clinical-trial proposals point in the right direction: faster assessments, reusable product information, more proportionate procedures and better coordination between Member States. The Clinical Trials Regulation has been applied for nearly five years, and its lessons are visible in the text.

But getting there means changing most of the regulatory infrastructure EU clinical trials run on, on a fixed timetable, while the rules are still being written. The challenge for sponsors will not only be understanding the final legislation. It will be knowing which requirement applies, from which date, in which CTIS version, to which ongoing trial and which version of which core dossier.

Where RafiHive fits

RafiHive answers from a reviewed knowledge base of official EU/EEA regulatory sources, with each document's legal status and version recorded. A question about substantial modifications today is answered against Regulation (EU) No 536/2014 and current CTIS guidance. The Biotech Act proposal is a proposal, and it is marked as one rather than presented as current. When the final text, the implementing acts and the new CTIS guidance are published, they become sources with a status and an application date — the distinction a two-regime transition depends on.