1. Lessons Learned: Past Present and Future Japan-USA Regulatory Interactions
Erica Takai, PhD
US Food and Drug Administration

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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. Who Do I Contact? FDA Contact:
Dr. Bram Zuckerman, Director, Division of Cardiovascular Devices,
Carole Carey, Director, International Relations & External Affairs Staff, Division of Small Manufacturers, International and Consumer Assistance,
MHLW Contact: Kentaro Azuma, Deputy Director, Office of Medical Devices Evaluation, MHLW, 10

11. Where Can I Find Out More?
General information, announcements, and updates on future meetings:
For copies of slides: 11

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