1. 1 The European Paediatric Initiative Agnès Saint Raymond, MD Scientific Advice and Orphan Drugs The European Medicines Evaluation Agency

2. 2 The EU System Two European procedures for marketing authorisation from January 1995 (Regulation 2309/93): centralised (biotech and innovative medicines) mutual recognition (all except biotech) Creation of the European Agency for the Evaluation of Medicinal Products (EMEA) Rapid and EU-wide authorisation for innovative medicines (210 days) One evaluation, One authorisation, 11-13 languages!

3. 3 The EMEA EMEA is not an FDA for Europe! Member States have pooled their sovereignty for authorisation of medicines EMEA coordinates the existing scientific resources of Member States An interface with all partners All parties linked by an IT network (EudraNet)

4. 4 EMEA and the EU system Committee for Proprietary Medicinal Products (CPMP) Committee for Proprietary Medicinal Products (CPMP) Committee for Veterinary Medicinal Products (CVMP) Committee for Veterinary Medicinal Products (CVMP) Committee for Orphan Medicinal Products (COMP) Committee for Orphan Medicinal Products (COMP) EMEA Management Board EMEA Management Board National competent authorities 2,500 European experts National competent authorities 2,500 European experts EU institutions: Commission and Parliament

5. 5 CPMP: Licensing scientific committee Chairman: Dr. Daniel BRASSEUR 2 Members /15 Member States + Repres. from Norway and Iceland + European Commission

6. 6 Working Parties CPMP + Ad-hoc EXPERT GROUPS: e.g. : Paediatric Expert Group, Bioterrorism, Oncology, Anti HIV drugs Biotech WP Prof. J.H. Trouvin Safety WP Prof.B. Silva Lima Quality WP Dr. J.L. Robert Blood and Plasma WP Dr. M. Haase Efficacy WP Dr. B. van Zwieten Boot Pharmacovigilance WP Dr. A. Castot

7. 7 The EU situation 20% of the EU population, ie 75 million, is aged less than 16  46% medicines prescribed to children either unlicensed or off-label (hosp) 1  67% of children receive unlicensed/off- label medicines (hosp) 1  Up to 90% of ICU paediatric medicines are not licensed 2 1 Conroy S et al. Br Med J. 2000;320:79-82 2 Chalumeau M et al. Arch Dis Child. 2000;83: 502-5

8. 8 European Initiative l Round table on Medicines for Children 1997 l French Memorandum in July 2000 l Council Resolution in December 2000 l Consultation Paper Feb 2002  April 2002 l Draft Legislation 3Q 2002 l Council and European Parliament readings l Implementation in 2003-2004?

9. 9 PEG objectives l Co-ordination of paediatric actions, advice on paediatric development (Guidelines) and market access l Needs / Priorities for studies of products l Information (web) between MS, to Health professionals and the public l Relations with patients, industry, learned societies and other Agencies

10. 10 l 14 Experts, and ‘Links’ with COMP and Working Parties l Experts proposed by Member States l Composition based on expertise at difference of other groups. Paediatric Expert Group

11. 11 PEG composition l Paediatric formulations: 1 pharmacist l Preclinical requirements: 1 preclinical expert l Methodology: 1 ‘Bayesian’ expert l PK and pharmacology: 2 l Clinical efficacy: 8 »Neonatology, Adolescent medicine, G al Paediatrics, Immunology, Nephrology l Pharmacovigilance: 1 from National Agency (vaccines) l Links with existing COMP and Working Parties: 5 + Observers

12. 12 Ad-hoc group on Paediatrics MRFG CPMP PEG Networking COMP CPMP, Working Parties + Ad-hoc groups

13. 13 Paediatric formulations l Paediatric formulations of choice l List of most used adult medicines l Extemporaneous preparations (hospital pharmacists) - Good Practice guide

14. 14 Preclinical issues l Concept Paper on Toxicity studies in Juvenile animals l Review of existing data Are we adding useful requirements or are we setting disincentives?

15. 15 Methodology l A problem common to Orphan drugs and Paediatrics l Clinical trials for efficacy and small sample size l Inventory of existing methods l Introduction into methodology guidelines Meeting on 22 October 2002 at the EMEA

16. 16 Inventory of the needs l Existing compendia (UK, France, Sweden) l Published information l US studies l French Data l Harmonising the needs l Setting priorities In view of (public) funding of studies Developing network of paediatric investigators

17. 17 Paediatric pharmacovigilance l Long-term surveillance l New requirements – cohort, register, l Post authorisation studies l Funding?

18. 18 All products with indication in children l From all European sources l According to age groups l Extrapolation of data, or specific? l In the future, paediatric EPARS? Database of Products

19. 19 There is a need for a European regulatory framework In the mean time, practical actions to be taken with the PEG - Needs and Priorities - Information - Awareness - Networking Conclusions