Clinical trials are investigations in humans intended to discover or verify the effects of one or more investigational medicinal products ("IMPs").
Requirements for the conduct of clinical trials in the EU are provided for in the "Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use" (the "Clinical Trials Directive") .
On 16 April 2014 the new Regulation EU No 536/2014 of the European Parliament and of the Council on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC (the "Clinical Trials Regulation") was adopted, and published in the Official Journal on 27 May 2014.
The Clinical Trials Regulation aims to create an environment that is favourable for conducting clinical trials, with the highest standards of patient safety, for all EU Member States. Intrinsic to this is the simplification of current rules, for example:
- A streamlined application procedure via a single entry point - an EU portal and database, for all clinical trials conducted in Europe. Registration via the portal will be a prerequisite for the assessment of any application;
- A single authorisation procedure for all clinical trials, allowing a faster and thorough assessment of an application by all Member States concerned, and ensuring one single assessment outcome and authorisation per Member State;
- The extension of the tacit agreement principle to the whole authorisation process which will give sponsors and researchers, in particular SMEs and academics, more legal certainty;
- Strengthened transparency for clinical trials data.
The Regulation entered into force on 16 June 2014 but will apply no earlier than 28 May 2016.
Transition between Directive 2001/20/EC and Regulation EU No 536/2014
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 This Directive will be repealed on the day of entry into application of the Clinical Trial Regulation. It will however still apply three years from that day to:
- Clinical trials applications submitted before the entry into application (no earlier than 28 May 2016);
- Clinical trials applications submitted within one year after the entry into application if the sponsor opted for old system.
The Commission Directive 2005/28/EC of 8 April 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products (the "GCP Directive") will apply to the clinical trials submitted under the Directive until the end of transitory period. For the clinical trials submitted on the basis of the Regulation new Implementing Regulation on detailed arrangements for inspections procedures on GCP, including qualifications and training requirements for inspectors will apply.
The Commission Directive 2003/94/EC of 8 October 2003, laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use (the "GMP Directive") will continue to apply to all clinical trials authorised under the Directive 2001/20/EC until the end of transitory period. A new Delegated Regulation will be adopted to set the GMP rules for Investigational Medicinal Products and will apply to all clinical trials authorised on the basis of the Clinical Trials Regulation.
For more information on the state of play of the Commission implementing measures required by the Clinical Trials Regulation click here.
There are a number of guidelines further specifying various aspects of clinical trials.
These guidelines have been published by various bodies:
- By the European Commission: In this case, they are published in EudraLex - Volume 10.
- By the European Medicines Agency ("EMA") These guidelines concern in particular:
- Moreover, the Heads of Medicines Agencies have established a Clinical Trials Facilitation Group ("CTFG") (in which the Commission and EMA are observers), in order to discuss ongoing technical issues.
The guidelines for the application of Clinical Trials Directive can be found here.
The relevant guidelines and recommendations are now being revised and updated to be in line with the changes and requirements of the Clinical Trials Regulation.
Revision of Clinical Trial Directive
Preparation of the Commission proposal
In its Communication of 10 December 2008 to the European Parliament, the Council, the European Economic and Social Committee and the Committee of the Regions on "Safe, Innovative and Accessible Medicines: a Renewed Vision for the Pharmaceutical Sector", the Commission announced that an assessment would be made of the application of the Clinical Trials Directive.
This assessment considered, in particular, various options for improving the functioning of the Clinical Trials Directive with a view to making legislative proposals, if appropriate, while taking the global dimension of clinical trials into account.
A "roadmap" of the Commission impact assessment, setting out the main structure and the next steps, was made available here.
On 9 February 2011, a public consultation on a concept paper on the revision of the "Clinical Trials Directive" 2001/20/EC was launched. The concept paper presented:
- A "preliminary appraisal" of which option appeared to be the most suitable one to address some of the key concerns of the Clinical Trials Directive, on the basis of the current state of the impact assessment; and
- the main figures used to evaluate the impacts of the different policy options.
Adoption of the proposal for a "Clinical Trials Regulation"
On 17 July 2012, the Commission adopted a "Proposal for a Regulation of the European Parliament and of the Council on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC" (hereinafter the "Clinical Trials Regulation") .
In addition, a "citizen summary" was published.
The proposal was submitted to the European Parliament and the Council who engaged in ordinary legislative procedure. You may find an overview of this procedure here. To follow the proposal in the different steps of the procedure, please consult the "legislative observatory" of the European Parliament or PreLex, the EU-database on interinstitutional procedures.
Adoption of the new Regulation on clinical trials
On 16 April 2014 the new Regulation No 536/2014 of the European Parliament and of the Council on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC was adopted, and published in the Official Journal on 27 May 2014. It entered into force on 16 June 2014 but will apply no earlier than 28 May 2016.
Until then the Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use(the "Clinical Trials Directive") will still apply.
In addition, the transitory provisions of the Regulation offer the sponsors the possibility to choose between requirements of the Directive or the Regulation for 1 year from the entry into application of the regulation.