Lessons Learned: Past Present and Future Japan-USA Regulatory Interactions Erica Takai, PhD US Food and Drug Administration erica.takai@fda.hhs.gov

Erica Takai DISCLOSURES I have no real or apparent conflicts of interest to report.

Getting safe and effective devices to market as quickly as possible… US FDA’s Mission Getting safe and effective devices to market as quickly as possible… …while ensuring that devices currently on the market remain safe and effective. To promote and to protect the public health of our citizens in a science led manner Global Harmonization is major goal for FDA The convergence of medical device development will result in increased efficiency 3

Challenges with Drug-Eluting Stent Global Clinical Trials Potential difficulties in patient poolability Differences in patient demographics Differences in clinical practice patterns Availability of concomitant drug therapies Procedural use of intravascular ultrasound and angiographic follow-up Clinical trial infrastructure challenges Challenges can be overcome with creative clinical trial designs and good planning 4

Previous DES Experience: Leveraging Japanese Data Medtronic Endeavor Similar PK profile for Zotarolimus in US and Japan PK studies No ethnic differences in PK after adjustment for body weight differences No clear pathway for US & Japanese regulators + Sponsor discussions existed 5

Collaborative Scheme for Consultation and Review Paradigm for US and Japanese regulators to discuss device and trial information and/or regulatory submissions US and Japanese Regulators work together with sponsor toward solutions Include sponsors in 3-way communications as appropriate Protect confidential and trade secret information Does not adversely affect US approval time lines 6

Collaborative Scheme Goals Improve the consultation and review process by exchanging scientific and regulatory views Facilitate the review of one acceptable clinical trial protocol by both regulatory agencies “simultaneously” Eliminate/reduce redundancies, added costs, and time delays inherent in duplicative trials Sharing of scientific and regulatory views expected to enhance (not hinder) review process Ultimately decrease time-lag in obtaining market approval 7

Progress of Collaborative Scheme Announcement for solicitation of projects posted June 15, 2009 Two projects selected jointly by US FDA and MHLW/PMDA (one from each country) 2 Superficial femoral artery stent devices chosen 7 not selected were offered a one-time collaborative interaction Currently limited to cardiovascular devices Regulators have monthly telecons 8

Future Directions Regulatory submissions and consultations Continue to develop processes for the Collaborative Scheme Provide public updates while protecting confidential and trade secret information General scientific topics: Procedural vs protocol driven angiography Pooling data for pediatric devices Race and gender differences Is body size a more predominant factor? Please share your global clinical trial experience 9

Who Do I Contact? FDA Contact: Dr. Bram Zuckerman, Director, Division of Cardiovascular Devices, bram.zuckerman@fda.hhs.gov Carole Carey, Director, International Relations & External Affairs Staff, Division of Small Manufacturers, International and Consumer Assistance, carole.carey@fda.hhs.gov MHLW Contact: Kentaro Azuma, Deputy Director, Office of Medical Devices Evaluation, MHLW, azuma-kentaro@mhlw.go.jp 10

Where Can I Find Out More? General information, announcements, and updates on future meetings: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/InternationalInformation/ucm053067.htm For copies of slides: erica.takai@fda.hhs.gov 11

Center for Devices and Radiological Health Thank You Center for Devices and Radiological Health C D H R