Office of Medical Devices II, Points To Consider in the Review of Endovascular Treatment Devices: Japanese Regulatory View Shin Iwamoto, Ph.D. Office of Medical Devices II, PMDA, Japan HBD WG1 secretariat

Shin Iwamoto, PhD  I have no relevant financial relationships

PMDA’s Mission To provide safer and more effective pharmaceuticals and medical devices as fast as we can Risk Benefit

Development Support from PMDA R&D Non-clinical study Clinical study Application Market Consultation Next-generation Evaluation Indicator and the Science Board Streamlining of Process : SAKIGAKE

Global Clinical Trial Through HBD Activity Conducted US-Japan joint clinical trials for two DESs - ENDEAVOR（Medtronic Japan Co., Ltd.） - XIENCE V（Guidant Japan K.K.（then）） Place of discussion needed on the issues associated with conducting the joint clinical trial with single protocol → HBD WG1 has inherited duties Global clinical trials for Coronary DESs and peripheral stents have been conducted. Paved the way for the global clinical trials 　　　　　　　　　　 Proved By Doing that conducting global clinical trials is possible. → Global clinical trial is now common for MDs. Global clinical trials

Steps Taken in CLI-experts’ Activity ・Conduct global clinical trial using the one protocol in the US and Japan in the future Identify mutually agreeable points Propose the outline of the clinical trial, taking into account the differences between Japan and the US Survey on current situations in Japan and the US Identify and clarify differences Understand what are already practiced in each country 6 Based on shared perspectives, the goal is to have CLI studies using one protocol in the US and Japan from now on 6

Lessons learned from the CLI-Sub WG activity 1.Providing the basic concept of global clinical trial during device development - We could propose the concept of evaluation method while the device is still under development for treatment of CLI - Concepts could be proposed after understanding the differences in 　 　medical environment between the US and Japan. 2. Mutual understanding among US and Japan academia and regulators has been promoted Academia Expectation for promoting the discussion about DCB treatment efficiently using the framework of CLI Regulatory Industry

Current Situation of CLI patients in Japan CLI patients have severe calcified lesions with greater disease - Over 50% of CLI patients in Japan are on dialysis - The majority of CLI patients have comorbid conditions of diabetes mellitus - There are more Rutherford Class 5 patients than Class 4 Iida O. et al, CCI 2013;6:68-76 - Approved DCBs devices for peripheral lesion are not available 10-20% Hemodialysis > 50% Class 4 > 5 Rutherford Class 5 > 4

Points to Consider in the review of DCBs Treatment for peripheral lesion Concept：Reduction of restenosis with anti-restenotic drug Effectiveness：Superior treatment outcome (vessel patency or freedom from TLR) compared with POBA Safety: Drug-related adverse events (distal emboli) Endovascular today 2014 December Supplement

For Appropriate Evaluation The Development of New Indication for DCB Bleow the knee Arteriovenous fistulas (AVFs) for dialysis, etc. Regulatory Academia Industry HBD Sharing information and constructive discussions among the stakeholders can lead to mutual understanding and solving problems Contribution to the development of peripheral vascular devices

Thank you for your kind attention! Shin Iwamoto, Ph.D. Office of Medical Devices II PMDA, Japan iwamoto-shin@pmda.go.jp For more information, please visit our website: URL :http://www.pmda.go.jp/