Clincal Trials Regulation (EU) No 536/2014 in Practice

This resource is developed as a quick guide to provide sponsors and investigators with a practical overview of the rules and procedures under the Clinical Trials Regulation (EU) No 536/2014, while clarifying that only the legislative text and, ultimately, the Court of Justice can provide an authoritative interpretation. It is part of “The rules governing medicinal products in the European Union – Volume 10, Guidance documents applying to clinical trials”, with version 05 adopted by written procedure in the Clinical Trials Coordination and Advisory Group (CTAG) and published on 1 March 2024.

Before the trial, it covers:

• key principles of the Clinical Trials Regulation and the transition from the Clinical Trials Directive
• feasibility and preparation of the clinical trial dossier (protocol, insurance or compensation, safety surveillance set‑up)
  user registration and access management for the Clinical Trials Information System (CTIS), including sponsor and organisation roles
• registration of medicinal products in the eXtended EudraVigilance Medicinal Product Dictionary and handling of auxiliary medicinal products
• composition and submission of the clinical trial application in CTIS (forms and Member States concerned, Part I, Part II, language and national requirements).

During the trial, it explains:

• applications for substantial modifications and relevant non‑substantial changes
• adding new Member States concerned to an authorised trial
• safety surveillance responsibilities, including adverse events, serious adverse events, suspected unexpected serious adverse
• reactions, annual safety reports, serious breaches, urgent safety measures and temporary halts
• other mandatory notifications in CTIS, such as start of trial, first patient first visit and end of recruitment, with timelines summarised in an annex.

After the trial, it describes:

• notifications of the end of a trial or early termination at national, European and global level
• submission of summary results and layperson summaries within defined time‑frames
• clinical study report submission when a trial supports marketing authorisation
• archiving of the clinical trial master file and subject medical records.

Additional sections provide guidance on CTIS transparency, protection of commercially confidential information and personal data, and specific considerations for advanced therapy products, genetically modified investigational medicinal products and complex or decentralised clinical trial designs, with references to further European guidance and training materials.