Laboratoires MSD-Chibret 12 Feb 2007

1. Laboratoires MSD-Chibret 12 Feb 2007 1 Commitment / Issues & solutions / BUSINESS IMPACT LROP / SFA Part of our Plan to Win Part of our New Commercial Model One of the major challenges that we face in the french market is the access to physicians So the SGL team have been piloting programs over the last 3 years in order to define a strategy to help our reps reach DTAP Commitment / Issues & solutions / BUSINESS IMPACT LROP / SFA Part of our Plan to Win Part of our New Commercial Model One of the major challenges that we face in the french market is the access to physicians So the SGL team have been piloting programs over the last 3 years in order to define a strategy to help our reps reach DTAP

2. Laboratoires MSD-Chibret 12 Feb 2007 2 Commitment / Issues & solutions / BUSINESS IMPACT LROP / SFA Part of our Plan to Win Part of our New Commercial Model One of the major challenges that we face in the french market is the access to physicians So the SGL team have been piloting programs over the last 3 years in order to define a strategy to help our reps reach DTAP Commitment / Issues & solutions / BUSINESS IMPACT LROP / SFA Part of our Plan to Win Part of our New Commercial Model One of the major challenges that we face in the french market is the access to physicians So the SGL team have been piloting programs over the last 3 years in order to define a strategy to help our reps reach DTAP

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5. Laboratoires MSD-Chibret 12 Feb 2007 5 Modification and study ending CA / EC

6. Laboratoires MSD-Chibret 12 Feb 2007 6 Partnership MSD-France and Afssaps in Clinical Trials

7. Laboratoires MSD-Chibret 12 Feb 2007 7 Afssaps Pilot Phase Thanks to a 2 1/2 years of Pilot Phase : a very compliant transposition was implemented in France on 27 August 2006 MSD-France participated in 19 CT under Afssaps Pilot Phase in many therapeutical areas as HIV, Obesity, Oncology, Osteoporosis� Collaborative partnership has lead to quality assessment of files and to proactive communication with Afssaps Efficiency and expertise increased to assess clinical trial files ? Afssaps was well prepared and organized to move to new regulation and clinical development is become a strategic vision of Afssaps

8. Laboratoires MSD-Chibret 12 Feb 2007 8 Afssaps General organization chart

9. Laboratoires MSD-Chibret 12 Feb 2007 9 Medicinal and Biological Products Evaluation Directorate

10. Laboratoires MSD-Chibret 12 Feb 2007 10 Clinical Trials and Drugs with Specific Status Evaluation Department

11. Laboratoires MSD-Chibret 12 Feb 2007 11 Afssaps Clinical Trial Unit (CTU) ? Specific unit dedicated to the evaluation of Clinical Trials Application : � clinical evaluation � pharmaceutical evaluation � viral safety evaluation � preclinical evaluation ? Linked to external experts and to internal experts ? Closely work with �Authorization Temporary Use� Unit to give to the patients an early access to new drug ? French Agency CTU involved at the European level to support harmonization of evaluation, strong Leadership to give recommendations

12. Laboratoires MSD-Chibret 12 Feb 2007 12 Afssaps new regulation Metrics 2006

13. Laboratoires MSD-Chibret 12 Feb 2007 13 Specificities of Afssaps requests Questions raised by agency Clinical Unit assessors : ? Administrative (technico-regulatory) check the presentation of the data ? Pharmaceutical : focused on sterile product, impurities and comparison between the dossier and the registration data if applicable ? Pre-clinical : human dose versus animal dose ? Clinical : safety of the patients including the safety of the drugs and the correct use (compliance with local SPC of registered drug if applicable �)

14. Laboratoires MSD-Chibret 12 Feb 2007 14 Strengths for Agency approval Afssaps communicates easily and is opened to negotiation during evaluation : transparency and predictibility in Clinical Trial Unit of Afssaps Day 1 for Clock Start is at the reception of a complete dossier by agency No clock-stop during the process : 14 days from agency questions to sponsor answers Phase I quick assessment commitment (< 30 days) Easy notification for biological collection (ex: genetic samples) entered in the CSA at the submission -> to perform the genetic analysis through a clinical trial ��Non Investigational Medicinal product�� completely implemented in French Regulation (decrease cost and workload for sponsors) AFSSAPS is one of the LEADER in Europe to push the Members states to an European Doctrine facilitating the clinical trials in Europe (Clinical trial facilitation group, members of GMP annex 13 and GCP teams �)

15. Laboratoires MSD-Chibret 12 Feb 2007 15 Weaknesses for Agency approval If uncomplete documents at the submission, the dossier is not Admissible and clock start is delayed until reception of missing documents : 45% of dossiers were not admissible in 2006 French Specificities regarding the dossier to submit : Viral safety dossier for biological products used in investigational medicinal product not registered : Afssaps evaluates both VIRAL and TSE risk of transmission in addition to the European current Guidelines on TSE Authorization for pharmacy to prepare infusion drugs � Agency Internal communication between registration assessors and clinical trials assessors should be improved especially for drugs that are on registration process

16. Laboratoires MSD-Chibret 12 Feb 2007 16 Conclusion The Pilot Phase has given a strong advantage to Afssaps and has demonstrated Competitive approval timelines under new regulation versus other Members States competent authorities : national mean 2006 approval time => 35 days Ethic committee median approval time for MSD France is 35 days, single and competitive as well among the Members states But competition is worlwide � Afssaps and MSD-France have a strong willingness to sustain and develop clinical research in France, in adequation with the European regulation and to participate in early Phase of clinical trials until Phase IV to deeply support a quick registration of the innovative drugs giving a real benefit for the patients

17. Laboratoires MSD-Chibret 12 Feb 2007 17 BACK UP

18. Laboratoires MSD-Chibret 12 Feb 2007 18 Competence fields for evaluation CPP (EC) Protection of participants ? Consent form / Information / modalities ? Modalities of recruitment ? Period of exclusion ? Compensation for participants Research ? Pertinence ? Satisfactory character of Benefit/risk assessment ? Involvement of data monitoring committee Means ? Adequacy objectives and means ? Qualification of investigators ? Mean at Site level

19. Laboratoires MSD-Chibret 12 Feb 2007 19 Strengths for ERC approval process Often 2 sessions per month Sponsor submit the dossier to the ERC directly Good communication before and after submission Sponsor/inv coord can present the protocol during the session Mean for ERC approval is 44 days after filing for MSD France, median is 35 days Choice of ERC committee is multiple into an interregion

20. Laboratoires MSD-Chibret 12 Feb 2007 20 Weaknesses for ERC approval process Many questions on the Informed consent to be reviewed at the next session Clock-stop at ERC sending questions until reception of the sponsor answers ERC questions is not very predictible No ERC approval obtained after the first session since new regulation