Birka Lehmann EUROPEAN COMMISSION Enterprise Directorate-General Pharmaceuticals Unit

1. Special populations-What makes them so special?AGAHAssociation for Applied Human PharmacologyAnnual meeting 2004 Berlin 29. Februar 2004 Birka LehmannEUROPEAN COMMISSION Enterprise Directorate-GeneralPharmaceuticals Unit

2. Richtlinie 2001/20/EG DES EUROPÄISCHEN PARLAMENTS UND DES RATESDirective 2001/20/EC of the European Parliament and of the Council of 4 April 2001 and published 1/5/2001

3. 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)

4. Directive 2001/20/EC Article 22 Implementation in national legislation AT ? IR ? BE ? IT DK LU ? DE ? NL ? EL ? PO ? ES SE FI ? UK ? FR ?

5. Directive 2001/20/EC Article 1 Good clinical practice →new Directive&Guideline Articles 6 - 8 Ethics Committee → guidance Article 9 Competent authorities → guidance 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

6. 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

7. 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 SPONSOR Competent Authority Start of the Trial

8. 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 SPONSOR Investigator Ethics Committee Competent Authority Competent Authority Investigator

9. Guidancepublished 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

10. 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

11. Guidancepublished 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

12. European database The European clinical trial data base &European database of Suspected Unexpected Serious Adverse Reactions

13. Europeandatabase • Dataset requires for allocation of a EudraCT number • Minimum core dataset for EudraCT: 1 May 2004 • Full acting system in place: 2005  Pilot-phase finalised

14. European database • Dataset for Eudravigilance database  Definition of inclusion of information in Clinical Trials Database OR Pharmacovigilance database for medicinal products with MA

15. 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

16. Directive/Guidelines awaited 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

17. Directive 2001/20/EC • Concerns raised by academic and researchers • Definition of Sponsor and responsibilities of the sponsor • Requirements of GMP • Bureaucraties

18. 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

19. Herzlichen Dank