Adding sites in the European Union means operating under the EU Clinical Trials Regulation, Regulation (EU) No 536/2014, which has applied since January 2022. Since the transition period ended in early 2025, trials in the EU run under the CTR, with applications submitted through the Clinical Trials Information System. US sponsors need to plan for a single coordinated application, fixed response deadlines, broad transparency and, in most cases, a legal representative in the EU.
What changed under the CTR?
The CTR replaced a patchwork of national processes with a single portal, CTIS, and a single application dossier. A reporting member state coordinates the assessment of the scientific and regulatory parts, while each member state assesses national aspects. Transparency is the default, with many documents becoming publicly available.
What does an application include?
Part I covers aspects assessed jointly by the member states concerned, including the protocol, investigator's brochure and investigational medicinal product dossier. Part II covers national aspects assessed by each country, such as informed consent, recruitment arrangements, site suitability, insurance and data protection.
Which timelines and deadlines matter?
The CTR sets fixed assessment timelines, and sponsors have short, fixed deadlines to respond to requests for information, measured in days rather than weeks. Missing a deadline can cause the application to lapse. Plan responsible people and backups for the response windows, especially around holidays.
What about transparency?
Many documents submitted through CTIS become public, with options to defer publication of some content. Plan in advance how you will handle commercially confidential information and personal data. Sponsors must also submit a summary of results, including a summary for laypersons, generally within one year of the end of the trial.
Do non-EU sponsors need a legal representative?
Generally, yes. A sponsor not established in the EU must have a legal representative there, although member states may waive the requirement in limited circumstances. Many CROs and specialist firms provide this service.
What else should US biotechs plan for?
A CRO with recent, hands-on CTIS experience. Time for national documents and translations. Data protection obligations under the GDPR. And investigational product logistics, including release by a Qualified Person for product manufactured outside the EU and country-appropriate labeling.
How should EU sites fit into your strategy?
Consider them early in the development plan rather than as a late enrollment rescue. A protocol designed with both FDA and EU expectations in mind avoids rework, and a well-planned EU application can broaden enrollment and support a future global registration strategy.
Keep reading: US-Only or Global for Your First Clinical Trial?
