Recent Think Tank Meeting Unites Japanese and US Regulatory Experts

During some of the hottest and most humid days of summer, approximately 120 representatives from the United States and Japan kept cool indoors during a recent think-tank meeting. Held July 22-23, this event sizzled—even inside the air-conditioned forum—as regulators, academic leaders and industry stakeholders held serious discussions about the state of regulatory affairs in Japan and the United States.

“Harmonization By Doing,” known simply as HBD, is an international effort to develop global clinical trials and address regulatory barriers to timely device approvals. Initiated in 2003 and spearheaded by Mitchell W.　Krucoff, MD, FACC, professor of medicine and cardiology at Duke University in Durham, NC, HBD holds thin- tank meetings to explore these issues and, hopefully, resolve and harmonize the existing barriers and deviations of regulatory approval processes and clinical trials for medical technology between the United States and Japan. The meetings, which discuss outstanding problems in the regulatory landscape, are held in both the United States and Japan. The first HBD Think Tank East meeting was held in December 2005 in Tokyo, and the first West event took place in January 2007 in Durham. Following on the heels of this summer’s East meeting, the next HBD West event will be held at Duke University in January 2009.

At the most recent meeting, Daniel G. Schultz, MD, director of the FDA’s Center for Devices and Radiological Health (CDRH), Krucoff, CDRH reviewers and representatives from the Washington, DC-based Advanced Medical Technology Association (AdvaMed) participated as speakers representing the United States. From Japan, Professor Ryozo Nagai, MD, from the Tokyo University School of Medicine, chaired the meeting. Representatives from the Ministry of Health, Labor and Welfare and Pharmaceuticals and Medical Devices Agency (PMDA), active physicians from academia and a representative of Japan’s Federation of Medical Device Associations participated as speakers.

The HBD meetings are organized by a steering committee and working groups. The functions of the steering committee include policy-making for the entire HBD, establishment and reinforcement of working groups, as well as determination of outcomes. Working groups consist of four teams, whose roles and function are summarized in Figure 1 (see page 38).

One of most prominent topics of HBD has been to explore the idea of developing a single protocol that could be used to conduct international clinical trials; the protocol also would help companies submit applications in both regions and have the documents evaluated simultaneously by each country’s regulatory agency. For now, this focus has been narrowed to cardiovascular devices only, but if the outcome of these meetings produces fruitful results, it will be expanded to other specialties more extensively by sharing common efforts among both countries’ regulators, academia and relevant industries. With this continuous effort, it is expected that each nation’s lag for approvals of new products—particularly in Japan—will be reduced and new advanced technologies will reach patients much quicker than today.

Various Topics Covered at the HBD Meeting

At the most recent East meeting, each working group reported its activities and outcomes determined to date and then followed up its report by holding interactive discussions with the audience.

The first team, Working Group 1, discussed the idea of developing a single protocol for conducting simultaneous clinical trials in the United States and Japan. This group’s objective is to enhance the global evaluation of new medical technologies by examining operational and regulatory challenges such as issues pertaining to data poolability, multinational randomization and integrated submission strategies. If the group’s goal of a single protocol is achieved, future trials may generate even more effective clinical data that could lead to faster approvals for both pre-marketing and post-marketing evaluation in both countries.

Working Group 2 is focused on post-marketing registries, with a specific initial interest in mechanical circulatory support systems, known as left-ventricular assist devices. The post-market information may become very useful not only for regulators, but also physicians and manufacturers in obtaining feedback pertaining to the safety and efficacy of these devices. In the United States, the focus is on the INTERMACS system, which was jointly developed by the National Heart, Lung and Blood Institute, the Centers for Medicare and Medicaid Services, the FDA, physicians, scientists and industry. Japan is planning to join the INTERMACS registry and share the database, which may facilitate more effective designs for international clinical studies and provide better opportunities to generate globally acceptable historical clinical data and ensure objective performance control. The group’s objective ultimately is to facilitate timely global introductions of new medical technologies through the identification of specific pre- and post-market barriers, as well as future post-market proof-of-concept projects that could be used to “test” possible solutions to barriers.

Meanwhile, Working Group 3 aims to improve the infrastructure of clinical trials in the United States and Japan. In spite of the power and size of these markets, the insufficient infrastructure for clinical trials in these regions has been a serious disincentive for the development of new medical technology. Therefore, the HBD working groups have recognized that the improvement of current infrastructures is an urgent issue for both countries. The progress by Working Group 3, which has discussed approaches to enhancing infrastructure and metrics for measuring improvements that could be tested with proof-of-concept projects, hopefully will produce changes to the infrastructure of clinical trials that will help introduce the new medical technology simultaneously in both countries.

Finally, Working Group 4 has focused on the enhancement of regulatory convergence and communications between the United States and Japan. The group’s study of the differences between each country’s regulatory system is intended to identify solutions to barriers that interfere with the timely introduction of new medical technologies to patients that need them. Although the Global Harmonization Task Force has focused on similar issues through its own activities, HBD’s Working Group 4 is working toward developing a more practical—rather than theoretical—approach to resolve problems based on the real-world experiences seen in everyday practices with bringing a new device to market in a timely fashion.

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Undoubtedly, think tanks can play an important role in forming policy as they generate ideas and recommendations that will aid future planning and strategy. Upcoming meetings of the HBD Think Tank will continue to focus on improving and sharing the understanding of each country’s regulatory system—and, hopefully, narrow the gaps between the two nations. Regulatory experts hope that these efforts also will expand more widely to benefit not only the large multinational companies, but also small/medium and even startup companies, as well as specialties beyond the cardiovascular sector. All medical industries involved are optimistic about the future, as they are expecting fruitful and productive outcomes from this dedicated effort.

Editor’s note: For more information about the HBD program, contact Hiroshi Yginuma (Japan MHLW) at hiroshi-yaginuma@ mhlw.go.jp or Carole C. Carey (US FDA) at [email protected]. Attendance at the HBD Think Tank meetings is open to the public.

Yoshio Mitsumori is the president and CEO for Tokyo-based ADMIS, a consultant specializing in the medical device industry. He has more than 25 years of experience in the medical industry, including positions with the Itochu Corp., U.S. Surgical, National Medical Enterprises and Century Medical. A member of RAPS, he has spoken at many industry events and worked extensively in international trade of medical products and technologies. He can be reached at [email protected].