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Clinical trials - Directive 2001/20/EC

Clinical trials in the EU are governed by the Clinical Trials Directive. Introduced to simplify and harmonise the administrative provisions governing clinical trials in Europe, it will be repealed by the Clinical Trials Regulation, upon its application in 2019.

The Regulation will improve legislation to address the disharmonised interpretation of the Directive across EU countries, and the administrative and regulatory burdens it imposed on the conduct of clinical trials.

The Directive will however, still apply three years from the date of application of the Regulation 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 old system

Guidelines

A number of these have been revised and updated to bring them in line with the changes and requirements of the Clinical Trials Regulation. All relevant documents will be progressively updated.

Application for the authorisation of Clinical Trials

The Clinical Trials Directive harmonises the rules for the approval of a clinical trial conducted in an EU country. The details are set out in the Commission Detailed guidance published in EudraLex - Volume 10.

EudraCT

The EudraCT database contains details on all ongoing or completed clinical trials falling within the scope of the Clinical Trials Directive. It enables competent authorities from EU countries, the EMA and the Commission to access information, interact, and maintain oversight of clinical trials and investigational medical products (IMPs) development. This ensures enhanced protection to clinical trial subjects and patients receiving IMPs.

EudraCT also contains information on trials conducted elsewhere in the world where they are part of an agreed paediatric investigation plan (PIP), or sponsored by a marketing-authorisation holder involving the paediatric use of an EU approved medicine, in line with Article 46 of the Paediatric Regulation.

Transparency

EU legislation requires that certain information contained in EudraCT be made accessible to the public. This is the case for clinical trials concerning paediatric as well as non-paediatric participants. It includes information on protocol and results.

Additional guidelines detailed in chapter V of EudraLex - Volume 10 consisting of three "mother guidelines" (Guideline 2008/C168/02, Guideline 2009/C28/01, Guideline 2012/C302/03), set out the principles, responsibilities, and procedural aspects of implementation. The "mother guidelines" are further concretised in detailed "daughter guidelines":

Protocol-related information is public under clinicaltrialsregister.eu, part of the public database EudraPharm.

Clinical trial results posted by sponsors in the EudraCT, in line with the Guideline 2012/C302/03, are available to the public, since 21 July 2014. This is outlined in European Commission guideline, in application of the current clinical trials Directive 2001/20/EC and the Paediatric Regulation.

What this means for clinical trial sponsors

  • For clinical trials that ended on or after 21 July 2014, sponsors will have to post results within six (paediatric clinical trials) or 12 months (non-paediatric).
  • For trials that ended before 21 July 2014, the guideline sets the specific timeframe for the results submission.

What this means for public access to information on clinical trial results

  • Some data included in EudraCT is available to the public in the European Union Clinical Trials Register, clinicaltrialsregister.eu.
  • Information on paediatric studies that ended before the Paediatric Regulation came into force in 2007 is also available in the Clinical Trials Register.

For all additional information, please click here.

Safety reporting

The Clinical Trials Directive sets rules on safety reporting in the context of a clinical trial. Details are set out in the "Commission detailed guidance on the collection, verification and presentation of adverse event/reaction reports arising from clinical trials on medicinal products for human use" published in EudraLex - Volume 10.

This guidance also provides rules for reporting suspected unexpected serious adverse reactions (SUSARs) to national competent authorities.

Clinical trials conducted outside the EU

Clinical trials conducted outside the EU which are submitted in an application for a marketing authorisation in the EU, must follow the principles equivalent to the provisions of the Clinical Trials Directive (cf. Annex I, point 8 of the Directive 2001/83/EC.

Contact points

Related information

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:

The Heads of Medicines Agencies established the Clinical Trials Facilitation Group ("CTFG") (in which the Commission and EMA are observers), in order to discuss ongoing technical issues.

Related information