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U.S. Department of Health and Human Services

Medical Devices

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Japan - U.S. "Harmonization By Doing" HBD Pilot Program Initiative

May 3, 2010 - Announcement of a Harmonization By Doing (HBD) Working Group (WG) 4 Summary Technical Documentation (STED) Proof of Concept (POC) Study

MHLW / PMDA and FDA are announcing the launch of a HBD WG 4 STED POC Study. The STED is intended to harmonize the evidence requirements and improve the consistency and efficiency of the conformity assessment process. The STED “retrospective” study (presented during the 2008 HBD East Meeting) demonstrated differences warranting “prospective” evaluation. It was also limited by the small number of STED submitted to date. To address this need for additional evaluation, this POC Study intends to collect and analyze regulatory submission data from multiple applications incorporating STED in the U.S. and Japan. The purpose of the study is to further understand differences that may exist with format and content, to define best practices and to improve processes. It is hoped that the information generated will promote further convergence between Japan and U.S. requirements for pre-market submission evaluations and review practices.

 What is HBD?

"Harmonization by Doing," commonly known as HBD, is an international effort to develop global clinical trials and address regulatory barriers that may be impediments to timely device approvals. This process is a cooperative effort to move both Japan and the U.S. toward international regulatory harmonization. Participants in this process include:

  • U.S. Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH),   
  • Japan's Pharmaceutical and Food Safety Bureau (PFSB) of the Ministry of Health, Labour, and Welfare (MHLW) and its review agency, the Pharmaceutical and Medical Devices Agency (PMDA),   
  • Duke Clinical Research Institute (DCRI),
  • Japanese academic community, and   
  • Japanese and U.S. medical device industry.  

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 What is the HBD initiative?

The HBD initiative is a pilot project launched in December 2003 that seeks regulatory convergence between FDA and MHLW-PMDA premarket review of device cardiovascular technology. Instead of taking a theoretical approach to harmonization, HBD will utilize parallel development, application submissions and review of actual medical device projects by FDA and MHLW-PMDA in conjunction with the above-named constituencies. The objective is to eliminate redundancies, added costs, and time delays inherent in sequential trials. The intent of HBD is not simply to create guidance and discuss policy but to develop common protocols for investigational clinical studies that would allow safe and effective "breakthrough" cardiovascular technologies to benefit patients worldwide.

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 What are the benefits of HBD?

FDA and MHLW-PMDA share similar scientific concerns and reviewers pose similar safety and effectiveness questions. While there may be divergence in regulatory practices, the two agencies are willing to consider ways of approaching the differences in order to allow the availability of novel treatments and innovative, safe and effective medical devices to patients more quickly. Only through international collaboration can global market reviews be conducted in a timely manner. HBD should provide:

  • more robust clinical trials
  • improved clinical research infrastructure
  • better clinical trial data
  • better understanding of how the U.S. and Japanese experience can complement one another
  • a new approach to early market availability of new treatment and devices to benefit patients in both countries
  • a mechanism to decrease lag time between U.S. and Japanese product approval
  • an atmosphere of international collaboration between regulators, regulated industry, clinical researchers, patients and academia
  • a continuous progression in global harmonization

HBD concept is also a process that can be broadened in scope beyond premarket activities. It can also be applied to postmarket clinical studies, collection of postmarket data and patient registries.

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 What does the HBD Pilot program hope to accomplish?

The undertaking of the pilot project is to provide a model for the full HBD program. As we continue to go forward and work together on all levels, we learn to share, develop and document best practices from a global perspective. The ultimate goal of the HBD initiatives is to reduce the amount of time it takes for a new therapy that has been demonstrated to be reasonably safe and effective using global, harmonized protocols conducted in patients worldwide to be available.

It is envisioned that, over time, HBD could expand to include other medical devices such as orthopedic products and others. As the HBD program matures, similar relationships with other regulatory bodies can also be developed in the future.

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 Where has HBD been and where is it today?

The vision of HBD had its beginnings several years ago. Its early roots began as a program in 1993 called "Heart Knows No Borders", led by Mitchell Krucoff, M.D. at DCRI, as part of the DOC-HHS-FDA regulatory harmonization working group in the U.S.-Israel Science & Technology Commission. From December 2003 to March 2004, joint meetings between FDA, MHLW-PMDA, DCRI and industry were held at the FDA to talk about the HBD concept and the HBD collaboration process. This was followed by other similar meetings at MHLW, and the first public announcement in a program at the Japan Circulatory Society in March of 2004. DCRI organized the first in-depth HBD East Think-Tank Meeting that took place in Tokyo in December 2005. Three main outcome goals surfaced from the 2005 Think Tank meeting: (1) Build a more robust clinical research infrastructure, (2) Compare medical device good clinical practices to determine if any significant differences exist that could be obstacles to the HBD process, and (3) Define and clarify the rules for increased and better cooperation among all parties involved.

An outcome of the Think Tank meeting resulted in the formation of the HBD steering committee and four working groups. Current participants in the steering committee and working groups include FDA, MHLW, PMDA, industry trade associations such as Advanced Medical Technology Association (AdvaMed) and the Japanese Federation of Medical Device Associations (JFMDA), and academia (DCRI and the Japanese academic community).

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  What is the current HBD Structure?

The following block diagram illustrates the structure showing the relationship between the Steering Committee and the Working Groups.

Proposed Structure of HBD

A Steering Committee is comprised of members from six constituencies, including the FDA, MHLW, DCRI, JAG (Japanese academic community/group), AdvaMed and JFMDA. The Steering Committee provides guidance and suggestions to Working Groups. Four initial working groups are identified as: 1) Global Cardiovascular Device Trials. 2) Post Market Registries (e.g., Artificial Heart). 3) Clinical Trials Infrastructure and Methodology. 4) Regulatory Convergence and Communication. Working groups provide reports and make requests back to the Steering Committee.The FDA and MHLW are responsible for high level review of the overall HBD program.

In general, the steering committee conducts telephone conferences monthly. Typically, the face-to-face meetings are held in conjunction with the Think Tank Meetings.

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  What are the Working Groups?

The Steering Committee felt that the key to the success of HBD is to develop practical achievable steps that would improve the process and advance the HBD program. There are four initial working groups. Each Working Group is developing their concept (mission) paper:

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 Why "Think Tanks"?

Shared meetings, "think tanks," and other related meetings help develop and facilitate the HBD program. A think tank generally refers to an organization or a group of individuals that researches specific problems, fosters provocative discussions among thought leaders in the field, facilitates interaction, and encourages the discovery of solutions to those problems.

Think tanks play an important role in forming policy. Think tank leaders provide ideas and recommendations pertinent to aspects of future planning and strategy. The main purpose of HBD think tanks is to continue the collaborative discussions that began two years ago. FDA, MHLW-PMDA, DCRI, industry, clinicians, academia and others are discussing and exchanging ideas to develop global clinical research studies for drug eluting stents under common protocols. Additionally, the think tank sessions offer a mechanism to explore real-time clinical trial examples. These examples will allow opportunities for proof-of concept projects, facilitating convergence of the regulatory processes between Japan and the United States.

A Think Tank East meeting was held in December 2005 in Tokyo, Japan. The first HBD Think Tank West took place in January 2007 in Durham, NC, U.S.A.

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 How can you participate in the "Think Tanks"?

Attendance to HBD Think Tank meetings is open to the public.

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 Think Tank Meetings Schedule

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