Transcript CLINICAL TRIALS DIRECTIVE

Special populationsWhat makes them so special?
AGAH
Association for Applied Human Pharmacology
Annual meeting 2004
Berlin
29. Februar 2004
Birka Lehmann
EUROPEAN COMMISSION
Enterprise Directorate-General
Pharmaceuticals Unit
Richtlinie 2001/20/EG
DES EUROPÄISCHEN PARLAMENTS UND DES RATES
Directive 2001/20/EC of the European Parliament and of
the Council of 4 April 2001 and
published 1/5/2001
Directive 2001/20/EC
Objectives:
Protection of subjects participating in clinical trials
Information on clinical trials - including database
Single decision by competent authorities
Single decision by Ethics Committees
Good Manufacturing Practice (GMP)
Good Clinical Practice (GCP)
Directive 2001/20/EC
Article 22
 Implementation in national legislation
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Directive 2001/20/EC
Article 1
Good clinical practice → new Directive&Guideline
Articles 6 - 8
Ethics Committee → guidance
Article
Competent authorities → guidance
9
Article 11
Eudract database, Exchanges of information →
guidance
Article 13.1
Manufacturing/importation authorisation
requirements for investigational medicinal
products → new Directive&Guideline
Article 15
Inspections (Inspection procedure, Qualification
of inspector) and Master file on the trial and
archiving → new Directive&Guideline
Article 17
Eudravigilance database → guidance
Directive on Good Manufacturing Practice
Directive 91/356/EC replaced by
 Directive 2003/94/EC of 8 October 2003
OJ L 262/22 14.10.2003
 Annex 13
Manufacture of investigational medicinal products
up-dated and published July 2003
The interaction between the Ethics Committees,
Competent Authority and Sponsor and in the European
Medicinal Product Legislation – before starting a clinical
trial
Ethics Committee
Investigator/Applicnat
Competent
Authority
SPONSOR
Start of the Trial
The interaction between the Ethics Committees,
Competent Authority and Sponsor and in the European
Medicinal Product Legislation - during conducting a
clinical trial
Amendments/
end of trial
suspension/
Adverse reactions
Ethics Committee
Investigator
Competent
Authority
Investigator
SPONSOR
Ethics Committee
Competent
Authority
Investigator
Competent
Authority
Guidance
published 23 April 2003 Commission web-site
 under review
Detailed guidance on the application format and documentation to be
submitted in an application for an ethics committee opinion on a clinical
trial on a medicinal product for human use
Detailed guidance for the request for the authorisation of a clinical trial on a
medicinal product for human use to the competent authorities in the
European Union, notification of substantial amendments and clarification of
the end of a clinical
Detailed guidance on the collection, verification and presentation of adverse
reaction reports arising from clinical trials on medicinal products for human
use
Directive 2001/20/EC
and
Guidance Documents
 Harmonisation:
Time-line for opinion by Ethics Committees (EC)
Time-line for ‘authorisation’ by competent
authorities (CA)
Application Form to EC and CA
Information on content of the dossier
Guidance
published 23 April 2003 Commission web-site
 under review
Detailed guidance on the European clinical trial data base
(Application form to EC and CA)
Detailed guidance on the European database of Suspected Unexpected
Serious Adverse Reactions
European database
The European clinical trial
data base
&
European database of
Suspected Unexpected
Serious Adverse Reactions
European database
 Dataset requires for allocation of a EudraCT number
 Pilot-phase finalised
 Minimum core dataset for EudraCT: 1 May 2004
 Full acting system in place: 2005
European database
 Dataset for Eudravigilance database

Definition of inclusion of information in Clinical
Trials Database OR Pharmacovigilance database
for medicinal products with MA
European database
 Directive 2001/20/EC = Member States, the Agency and the
Commission ONLY
 Regulation (EC) No …/2003/EC
Article 57 (1) (k) creating a database on medicinal products to
be accessible to the general public
Article 57 (2) … Where appropriate, the database shall also
include references to data on clinical trials currently carried out
or already completed, contained in the clinical trials database
for in Article 11 of Directive 2001/20/EC. The Commission
shall, in consultation with the Member States, issue guidelines
on data fields which could be included and which may be
accessible to the public
Directive/Guidelines 
Directive on Good Clinical Practice

Good Clinical Practice

Manufacture and import of investigational
medicinal products

Trial Master File and Archiving

Qualification of GCP inspectors

GCP Inspection procedures
awaited
Directive 2001/20/EC

Concerns raised by academic and researchers
•Definition of Sponsor and responsibilities of the sponsor
•Requirements of GMP
•Bureaucraties
Directive 2001/20/EC
Increased data requirements and application details compared to old
system  but unified format and contents of application
 Pharmacovigilance reporting system  different/selective approaches pointed
out in guidance documents
 Medicinal Product in accordance with Good Manufacturing Process  Patient
need assurance of high quality of medicinal product
Herzlichen Dank