1. Registration in Europe Current situation and future outlook Thomas K ü rner, M.D. Nippon Boehringer Ingelheim Co., Ltd.

2. Registration in Europe Authorities / organisation EMEA European Agency for the Evaluation of Medicinal Products –Management Board –Committee for Proprietary Medicinal Products (CPMP) –Committee for Veterinary Medicinal Products (CVMP) –Permanent Secretariat

3. Registration in Europe Authorities / organisation 2 scientific Committees ( CPMP & CVMP) : –objective high level scientific advice –proper co-ordination of work between the Agency and National Competent Authorities –Committee for proprietary Medicinal Products (CPMP) - 2 representatives from each MS –Committee for Orphan Medicinal Products (COMP)

4. COMP (Committee for Orphan Medicinal Products ® (1 member from each MS 3 members of patient organisations 3 EMEA Representatives) Scientific Committees CPMP for human products (2 member from each MS) Management Board (2 representatives from each MS, 2 from the Commission and 2 appointed by the European Parliament) CVMP for veterinary products (2 members from each MS) Executive Direction EXPERTS RAPPORTEURS WORKING PARTIES PERMANENT SECRETARIAT Administration validation of dossiers EXPERTS RAPPORTEURS WORKING PARTIES COMMISSION Standing committeeCOUNCIL Community decision AGENCY Registration in Europe

5. Marketing Authorisation Procedures How to market a medicinal product in the EU? European Centralised Procedure European Mutual Recognition Procedure European Community Appeal, Referral / Arbitration Post-Approval Procedures Specific Procedures

6. Registration in Europe Marketing Authorisation Procedures European Centralised Procedure –Granted by the European Commission –Valid in the 15 Members States of the EU –Mandatory for biotechnological products, »developed using the recombinant DNA technology »developed using hybridoma and monoclonal antibody methods –Optional for innovative medicinal products

7. Registration in Europe Marketing Authorisation Procedures European Mutual Recognition Procedure –Pre-requisite = Medicinal Product not falling under the scope of the Centralised Procedure –National Procedure => product will only be placed on the market of one Member State –As soon as more than one Member State, the Mutual Recognition Procedure must be used

8. Registration in Europe Marketing Authorisation Procedures European Mutual Recognition Procedure (Contn) –application submitted in one MS (Reference Member State = RMS) –once Marketing Authorisation has been granted: –identical applications submitted in the other Member States (Concerned Member States = CMS) –request to the CMS to mutually recognise the Marketing Authorisation already granted

9. Registration in Europe Marketing Authorisation Procedures European Mutual Recognition Procedure (Contn) –The RMS has an important role! »At the choice of the applicant »First marketing Authorisation in EU »Preparation of an assessment report »Co-ordination of the MRP between applicant and CMSs »Chair the Mutual Recognition Facilitation Group (MRFG)

10. Marketing Authorisation Procedures European Mutual Recognition Procedure (Contn) –The CMS is highly involved in the MRP! »Initiation of the MRP as soon as the 1st MA is granted »Recognition of the 1st MA within 90 days »Consultation of the Assessment Report prepared by the RMS »Member in the MRFG »National MA to be granted Registration in Europe

11. Marketing Authorisation Procedures European Centralised Procedure European Mutual Recognition Procedure Comparison - Pros & Cons

12. Registration in Europe Centralised Procedure 1 Health Authority 1 Application / 1 dossier 1 Assessment 1 Marketing Authorisation in 15 European countries +Norway +Iceland Mutual Recognition Procedure 1 harmonised dossier 1 harmonised Approval decision simultaneously up to 17 applications 17 national Authorities 17 marketing authorisations in single countries

13. Registration in Europe Centralised Procedure Proposal for rapporteur 1 Tradename 1 presentation Negative opinion of one MS influences EU wide decision 1 MA for the EU wide market procedure rather fast transparent process only one authority (EMEA) maintenance = 1 variation Mutual Recognition Procedure free choice of the RMS different tradenames possible national presentation possible possibility to withdraw a submission in specific countries if negative opinion up to 17 single MAs sometimes delay / national level decision process +/- transparent up to 17 authorities maintenance = up to 17 variations

14. Registration in Europe Marketing Authorisation Procedures Post-Approval Procedures (Contn): –Renewal »in Europe, the MA is valid for 5 years Specific situation of all new approved Products for the first 5 years: Periodic Safety Update Report (PSUR) 6 monthly - 2 years after authorisation Annually for the subsequent 2 years At the first renewal 5 yearly renewals »renewal mainly based on the pharmacovigilance data and the benefit to risk ratio »to be applied at least 3 months before expiry date

15. Registration in Europe Future outlook Revision proposed July 2001 To complete the single market To increase transparency To favour competitiveness of the industry To prepare EU enlargement

16. Registration in Europe Future outlook Revision proposed July 2001 Scientific expertise to be reinforced Increased scientific advice to companies (in particular for small sized companies & biotech companies) Faster access to highly innovative medicines –Fast track registration procedure –Conditional marketing authorisations

17. Registration in Europe Future outlook Innovation for the benefit of the patients Timeframes Centralised procedure: EMEA: from 210 days (normal authorization) to 150 days (fast-track); Decision-making: Member States consultation: reduced from 30 to 15 days; streamlined Commission procedure (new comitology); Expected total: +/- 270 days (currently +/- 1year) National procedures: from 210 days (now) to 150 days; Decentralised procedure: from 300 days (now) to 210 days. Target: all procedures below 1 year (International best average standard)

18. Registration in Europe Future outlook Promoting Industry competitiveness and competition Administrative Data protection periods to be harmonised between Member States (10 years) Possible one year extension in case of additional innovative indications bringing important clinical benefit for the patients Possibility for generic companies to perform trials before patent(s) expiry ( Bolar type provision)

19. Registration in Europe Future outlook Cutting the red-tape reduction paper flow Removal of the five year renewal rule for marketing authorisations Strengthening pharmacovigilance in particular through systematic electronic exchange of data Accelerated and simplified decision-making process