European Commission publishes updated Clinical Trials Guidance

23 April 2010

Mary Smillie

On 30 March 2010 the European Commission published updated guidance in relation to clinical trials. 

The documents updated included the “Detailed guidance for the request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities, notification of substantial amendments and declaration of the end of the trial” to the Clinical Trials Directive (2001/20/EC)[1] – this is the third version of this guidance document.  The Commission has also updated “The Guidance documents applying to clinical trials – Question & Answers Document” which is now the fifth version, and “Annex VI to Guidance for the conduct of GCP inspections - Record keeping and archiving of documents”.

All of these revised documents are now available in Volume 10 of Eudralex on the European Commission’s website.

Detailed guidance for the request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities, notification of substantial amendments and declaration of the end of the trial

The first revision of the “Detailed guidance for the request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities, notification of substantial amendments and declaration of the end of the trial” was published in April 2004[2], and revision 2 followed in October 2005 [3]. 

The new version 3 therefore comes after a period of over four years and is a substantial rewrite of revision 2.  This was required due to changes to the regulatory framework for pharmaceuticals and clinical trials in the European Union arising mainly as a consequence of the paediatrics legislation and the legislation on advanced therapies.  This version of the guidance now helpfully lists what it does not apply to, i.e. it does not apply to medical devices, cosmetic products and food.  In addition to the definitions in Directive 2001/20/EC, it also refers to other guidance documents for “valuable additional definitions”, so cannot be read in isolation.  It also defines the Member State where the clinical trial is to be performed as “Member State concerned”.

In terms of procedural aspects, there is now detail e.g. the time-lines for the Member State concerned to consider a request for authorisation of a clinical trial (as rapidly as possible and may not exceed 60 calendar days), and time-lines to be followed when an application is not considered valid. 

The layout of the guidance has been completely updated with clearer labelling of the paragraphs, and has been expanded with increased direct reference to the relevant Articles in Directive 2001/20/EC.

Notification of amendment is only required if it is a “substantial amendment”, and the guidance now has sections headed “the notion of ‘amendment’” and “the notion of ‘substantial’” and gives examples of substantial amendments in relation to assessment by the national competent authorities of the Member State concerned (not the Ethics Committee, which is subject to separate guidance). 

The summary tables which were at the end of version 2 of the guidance of the different national variations in requirements have been removed, which may indicate an increased level of harmonisation of requirements in the different Member States.

In line with these changes, the European Commission has also published a revised version of the clinical trials application form, which will become applicable in the course of the first half of 2010.  It has been published on the website in advance to allow stakeholders time for preparation. A precise date for when the new version of the clinical trials form becomes applicable will be published on the Commission website soon.







[1] Official Journal 2010/C 82/01-82/19 (30.03.2010)
[2] ENTR/CT 1 Revision 1 April 2004
[3] ENTR/F2/BL D (2003)  CT 1 Revision 2 October 2005