1. E5 Experiences in Japan Examples with unfavorable outcome How can we improve? Masuhiro Kato, PhD Chair, EFPIA Japan Technical Subcommittee (AstraZeneca Japan)

2. EFPIA Japan position on E5 guideline  We appreciate the positive efforts of MHLW in implementing the E5 guideline for Japanese development But there is still room for improvement:  The E5 GL should guide earlier access of global products to Japanese market through  Avoidance of repeated and/or duplicated clinical trials  Best use of the global clinical data set and experiences  Assurance for efficacy and safety in Japanese patients are of prime importance  The balance of the above two key factors should be agreed between the industry and the regulatory body

3. demography metabolism, genetic difference etiology diagnosis/disease classification inclusion/exclusion criteria endpoint (incl. surrogate endpoint) standard/concomitant therapy comparator epidemiology medical practice extrinsic factor: food, environment predecessors (class example) Dose Selection Safety Efficacy Study Design Conclusion from the survey Controversial Factors etc

4. Conclusion from the survey  Extrapolation of Western data to Japan  No clear standard or criteria on applicability of Western data to Japanese  “extrinsic factors” always win?  Inconsistency on judgment  Insists Japanese clinical outcome too much  In general, the balance is too far left on the scale All studies must be repeated No Japanese studies are needed

5.  How can we improve?  Collaborative workgroup (authority & industry) to standardize criteria  Future Pharmacogenomics/genetics elaboration could effectively solve some of the issues  Utilization of PMS for the confirmation of safety and efficacy  Further discussion required Conclusion from the survey

6. Q and A Summary Topics Need for Safety Data Considerations on Special Populations Multiple Indications Global Development Strategy/Global Study (Study Design Issues) Medical Practice Requesting One More Study Responsibility to Justify Bridging