Clinical trials are scientifically controlled studies undertaken in humans to establish or confirm the safety and effectiveness of investigational medicinal products (IMPs). The conduct of clinical trials in the EU is currently governed by the Clinical Trials Directive.
The Clinical Trials Regulation however, will replace the Directive. Its aim is to ensure a greater level of harmonisation of the rules of conducting clinical trials throughout the EU. It features:
- A streamlined application procedure for all clinical trials conducted in Europe via a single EU portal and database. All applicants must be registered before assessment
- A single authorisation procedure for all clinical trials, to allow a faster and more thorough assessment by all concerned EU countries
- The extension of the silent agreement principle to the authorisation process giving more legal certainty to sponsors and researchers, in particular SMEs and academics
- Strengthened transparency for clinical trials data
Although the Regulation entered into force on 16 June 2014 the timing of its application depends on the development of a fully functional EU portal and database by the European Medicines Agency together with the EU Member States and the Commission. The Regulation foresees that Regulation will be applicable six months after the Commission publishes a notice of “full functionality” that reflects the verification of the full functionality of the EU portal and database on the basis of an independent audit report.
European Medicines Agency (EMA)'s Management Board endorsed a delivery timeframe in December 2015. However, due to technical difficulties with the development of the IT systems, the portal’s go-live date had to be postponed. In December 2019, EMA's Management Board endorsed to commence the independent audit of the system in December 2020, following an audit readiness assessment carried out by the nominated product owners, EMA and the IT supplier. More information on the date of applicability will be made available as soon as possible. For further information please consult the EMA website.
Transition from the Clinical Trials Directive to Regulation
Until the Clinical Trials Regulation EU No 536/2014 will become applicable, all clinical trials performed in the European Union are required to be conducted in accordance with the Clinical Trials Directive. This Directive will be repealed on the day of entry into application of the Clinical Trials Regulation. It will however still apply three years from that day to:
- Clinical trials applications submitted before the entry into application
- Clinical trials applications submitted within one year after the entry into application, if the sponsor opted for the old system.
The Commission's GCP Directive will apply to clinical trials submitted under the Clinical Trials Directive until the end of transition period, except for the provisions in chapters 5 and 6 of this Directive which are related to inspectors and inspection procedures. These aspects will be covered by the Implementing Regulation (EU) 2017/556 of 24 March 2017 on detailed arrangements for the good clinical practice inspection procedures pursuant to Regulation (EU) No 536/2014 of the European Parliament and of the Council, which will become applicable at the same time as Regulation (EU) No 536/2014 and will apply to all GCP inspections (this means, inspections of clinical trials conducted under the Regulation as well as the Directive).
The Commission GMP Directive will be repealed by the new Commission GMP Directive 2017/1572 on the date of entry into application of the latter (i.e. the date of entry into application of the Regulation on Clinical Trials).
The Commission Delegated Regulation (EU) 2017/1569 of 23 May 2017 supplementing Regulation (EU) No 536/2014 will apply, as a matter of principle, to all clinical trials as of its entry into application. It specifies principles and guidelines for good manufacturing practice for investigational medicinal products for human use, and arrangements for inspections. This Regulation will also become applicable at the same time as Regulation (EU) No 536/2014. During the transitory period EU countries may however continue to apply their national law, adopted in order to transpose Directive 2003/94/EC, to those clinical trials conducted under the Directive 2001/20/EC. Additionally, the detailed Commission guideline, adopted on 8 December 2017, on the good manufacturing practice for investigational medicinal products, pursuant to the second paragraph of the Article 63(1) of Regulation (EU) No 536/2014 will become applicable as from the date of entry into application of Regulation (EU) 536/2014.
See more information on the state of play of the Commission implementing measures required by the Clinical Trials Regulation.
The Commission and Member States meet regularly in the Expert Group on clinical trials to discuss the implementation of the Clinical Trials Regulation. Agendas and minutes from the meeting are published on the Commission Register of Expert Groups.
Guidelines on the conduct of Clinical Trials
The guidelines for the application of Clinical Trials Directive can be found in Eudralex Volume 10. A number of relevant guidelines and recommendations have been revised and updated in line with the changes and requirements of the Clinical Trials Regulation. All relevant documents will be progressively updated.
The European Commission (EC), the European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) have co-signed a letter reminding all sponsors of clinical trials conducted in the European Union of their obligation to make summaries of results of concluded trials publicly available in the EU Clinical Trials Database.
Other guidelines are published by the EMA:
- Inspection procedures and guidance for GCP inspections conducted in the context of the Centralised Procedure
- Requirements relating to the quality, safety and efficacy of products, as well as specific types of products. See EudraLex - Volume 3.
- Clinical trials - Directive 2001/20/EC
- Clinical trials - Regulation EU No 536/2014
- Question and Answers on the interplay between the Clinical Trials Regulation and the General Data Protection Regulation
- Clinical trials - Key documents
- Clinical trials - Withdrawal of the United Kingdom and EU rules
- Clinical trials – Joint technical notice regarding preparedness for the withdrawal of the United Kingdom from the EU