Four Years In: What the EU Clinical Trial Regulation Has (and Hasn't) Delivered
When the EU Clinical Trial Regulation (EU CTR No 536/2014) went live for new submissions on January 31, 2022, it promised to transform how clinical trials are authorized and conducted across Europe: a single submission, one decision, and harmonized oversight. Four years in, the reality is more nuanced. The regulatory landscape, meanwhile, is moving faster than ever.
In a recent Xtalks webinar, four subject matter experts with direct experience navigating CTR and involved in the EMA-led initiative supporting CTIS development came together for a roundtable discussion on where the regulation stands today and where it’s headed. Pierre-Frédéric Omnes, Executive Director at TransPerfect Life Sciences, was joined by Gabriella Di Matteo, who leads EU-level advocacy and strategic engagement on EU CTR and CTIS at Pfizer; Scott Feiner, Senior Manager of Trial Disclosure at AbbVie; and Andrea Seidel-Glätzer, Managing Director of the KKS Network.
What follows draws on the key themes from their discussion and reflects what practitioners across the industry are watching most closely right now.
A Single System, but Not a Simple Journey
The Clinical Trial Information System (CTIS) launched as a "minimum viable product," in EMA's own words. And that label stuck. Early adopters navigated a system that changed almost continuously: constant CTIS fixes and evolutions, new workaround procedures, multiple guidance documents, and issues blocking users (both member states and sponsors) in their daily activities.
That era is largely behind us. But while the pace of change hasn't slowed, it has become more structured. The last 18 months alone have brought a revised transparency framework, a new non-substantial modification pathway, the end of both transition periods, and the launch of two major pilots: COMBINE (for combined IMP/IVD submissions) and FAST-EU (for accelerated assessment timelines). On top of that, the European Biotech Act proposal was published on December 16, 2025. While it’s still undergoing legislative review and is not expected to be officially adopted until 2027 or 2028, it carries significant implications for how the CTR will function going forward.
The Transparency Shift That Changed Everything
If there's one milestone that operational teams point to as genuinely transformative, it's the June 2024 implementation of the revised CTIS transparency rules.
Under the original framework, sponsors had to assume that virtually every document submitted to CTIS would be made public upon trial approval. That meant extensive redaction workflows, confidentiality assessments across the entire dossier, and significant administrative overhead built into every submission cycle and beyond (e.g., responses to RFIs and notifications).
The revised rules narrowed the mandatory disclosure scope considerably: protocols, protocol synopses, recruitment materials, and patient-facing documents are now the primary documents published at authorization. Everything else remains confidential. The practical result is fewer redactions, less pre-submission prep work, and more flexibility in how dossiers are assembled.
For large sponsors, this removed an entire layer of infrastructure that had been built specifically to manage CTIS transparency, allowing them to refocus mainly on legacy activities around results and clinical study report disclosure, which remain in place. For academic sponsors, who often lack dedicated regulatory affairs departments, it removed a barrier that had made CTIS submissions feel disproportionately burdensome.
What Still Needs Fixing
Despite real progress, several pain points persist, and they matter for submission timelines and operational efficiency.
1. Part I/Part II misalignment remains a genuine problem.
When Part I review generates questions that affect Part II documents—but the Part II clock has already run—sponsors are left submitting substantial modifications just to implement changes before recruitment can begin. This adds weeks to startup timelines and increases regulatory fees.
2. Sequential substantial modification submissions are another friction point.
The inability to submit parallel, mutually exclusive modifications means teams must queue changes that could otherwise be processed simultaneously.
3. IMPD-Q coordination is not yet well served by the current system.
Particularly for academic-industry collaborations where the quality dossier is owned by a party separate from the sponsor, IMPD-Q coordination requires workarounds that add overhead and risk.
4. Document management in CTIS has yet to meet sponsor expectations.
The management of documents continues to create downstream TMF filing challenges, though improved export functionality is in development.
The Biotech Act: Ambitious Scope, Measured Expectations
The European Biotech Act proposal, published in Q4 2025, contains one article (Article 58) dedicated to amending the EU CTR, with substantive changes such as:
- Shorter assessment timelines for both initial applications and substantial modifications.
- Parallel submission of mutually exclusive substantial modifications.
- Sequential Part I/II assessment, so Part II conclusions don't lock before Part I is final.
- An IMP core dossier concept with a designated Depositary Member State—a model with some functional similarity to the US Investigational New Drug (IND) framework, where a standing drug dossier is maintained separately from individual study applications.
- Combined IMP/IVD submissions via CTIS, codifying what the COMBINE pilot has been testing.
- Removal of the optional 50-day ATMP assessment extension.
- Reinforced RMS role and improved RMS-change procedures.
These are meaningful improvements. The shorter timelines in particular (already being stress-tested through the FAST-EU pilot) address what sponsors consistently identify as Europe's competitiveness gap relative to other regions.
The catch is that the Biotech Act is a full legislative proposal, not a regulatory update. It requires trilogue negotiation between the European Parliament, Council, and Commission. Realistically, a vote before the end of 2026 is optimistic; 2027 is more plausible. Add six to nine months for CTR-specific implementation, and sponsors shouldn't expect to operate under Biotech Act timelines before late 2027 at the earliest, with 2028 the more likely scenario.
The FAST-EU pilot offers a useful preview of what faster timelines will demand operationally: compressed RFI windows, coordinated member state task scheduling, and faster turnaround on redacted documents. Organizations that start stress-testing their workflows now will be better positioned when the new timelines become mandatory.
What to Watch in the Second Half of 2026
Several near-term developments also deserve attention:
- Email notifications for CTIS notices and alerts are expected by June 2026. This is a long-awaited operational improvement that reduces the need to monitor the system manually.
- The annual safety reporting module is planned for Q3 2026.
- The Article 11 partial submission workaround, launched in Q2 2026, offers sponsors a new pathway to manage complex submissions more flexibly, potentially reducing some substantial modification burden even before the Biotech Act.
- EMA's CTIS modernization roadmap will be presented to the Management Board ahead of summer, which should clarify the timeline for features like a sponsor API (currently targeting 2027–2028).
The Q&A landscape has also consolidated meaningfully. Three primary sources now cover the terrain: the EMA Sponsor Handbook (and its new Sponsor FAQs) for CTIS operational questions; the European Commission's Eudralex Volume 10 Q&A for legal interpretation; and the CTCG FAQ document for practical, cross-cutting operational guidance. Version 7.2 of the Commission Q&A, published in March 2026, introduced an important clarification on patient-facing document translations in Part II.
The Bottom Line
The EU CTR ecosystem is genuinely maturing, but it requires active monitoring. Guidance updates, pilot learnings, and CTIS releases continue to reshape what "standard practice" looks like. Organizations that stay close to the CTCG outputs, engage with initiatives like MedEthicsEU and ACTU, and use resources like pre-CTA advice for complex submissions will navigate this environment more efficiently than those relying solely on institutional knowledge.
The Biotech Act represents the most significant structural evolution since the EU Clinical Trial Regulation went live; however, the operational benefits are still years away. In the meantime, the tools and workarounds available today are more capable than they were 12 months ago, and using them well is a competitive advantage.
Hear It from the Experts
In the full Xtalks webinar, hear from Gabriella Di Matteo, Scott Feiner, Andrea Seidel-Glätzer, and Pierre-Frédéric Omnes on what the transition period actually demanded of their organizations, which readiness investments paid off, and which they would approach differently. They also discuss how pilots such as COMBINE and FAST-EU are already informing submission planning.
Watch the full episode to hear how experienced practitioners are preparing for the Biotech Act before its timelines become mandatory.
TransPerfect Life Sciences specializes in supporting the global development and commercialization of drugs, treatments, and devices, including navigating the evolving regulatory landscape in the EU. Speak with a regulatory expert to start the conversation.