Through the U.S. - Japan Medical Device Harmonization by Doing (HBD), the FDA, Japanese regulators, academia, and industry developed internationally agreed upon standards for global clinical trials related to cardiovascular devices, and addressed regulatory barriers that may delay timely medical device approvals in both countries.

The U.S. and Japan are also committed partners in the International Medical Device Regulators Forum, which is a group that works together to accelerate international medical device regulatory harmonization and convergence.

Activities:

Scientific Sessions
HBD organizes scientific sessions in conjunction with annual scientific conferences to promote regulatory convergence between FDA and MHLW premarket reviews and discuss advances in cardiovascular technology. In 2013, the Transcatheter Cardiovascular Therapeutics (TCT) Conference included a special session on HBD, 10th Anniversary Harmonization by Doing (HBD) at TCT: Novel Japan-US Synergy Research Opportunities in Global Medical Device Innovation.

Global Cardiovascular Device Clinical Trials
HBD has a workgroup focused on moving Japanese and U.S. clinical study sponsors and regulatory agencies toward the use of a single global clinical trial protocol for evaluating cardiovascular devices rather than parallel country-specific protocols. This would mean FDA may accept data from Japanese clinical studies using the joint protocols. Encouraging single global clinical trial protocols will facilitate device evaluation in both the U.S. and Japan by improving the timeliness and cost-effective generation of more informative clinical datasets for pre-market, and potentially post market evaluation. This will particularly benefit patients currently underserved by existing approved therapies.

Registries
HBD has a workgroup focused on standardizing information available in postmarket data registries, and reducing manufacturers’ premarket data requirements by using postmarket data. This workgroup developed and implemented the Japanese Registry for Mechanically Assisted Circulatory Support (J-MACS) registry, modeled after the U.S. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry. These registries collect and analyze clinical and laboratory data from patients receiving mechanical circulatory support devices for end-stage heart failure. The complementary datasets in these registries provide valuable information for improving the treatment of advanced heart failure patients in both countries. The workgroup is developing an International Consortium of Cardiovascular Registries to bring together registry information from multiple countries.

Other HBD Achievements:

• U.S.-Japan Collaborative Consultation and Premarket Review Pilot Program (2009-2012): This program allowed for cardiovascular device manufacturers to submit clinical datasets capable of obtaining marketing approval in both countries. The results were more robust clinical trials with greater ethnic diversity, and better safety and effectiveness data, as well as greater understanding and predictability of marketing approval expectations. Although the pilot has ended, medical device manufacturers that wish to submit clinical studies with single protocols in Japan and the U.S. can do so by discussing with regulatory reviewers in both agencies.
• Contributions to Good Clinical Practices: An HBD workgroup compared Japanese regulations, U.S. FDA regulations, existing international standards, and guidelines related to good clinical practices, and found no major differences in the fundamental criteria for ethical clinical research. HBD published the results of the study in April 2010. The results were considered in the 2011 revision of the ISO 14155 standard entitled, “Clinical Investigation of Medical Devices for Human Subjects-Good Clinical Practices.” In 2013, HBD published an updated study showing that one clinical investigation design accepted by multiple regulatory authorities improves acceptance of clinical investigation data, and can meet regulatory requirements for marketing approval. These studies were published in the Regulatory Affairs Professionals Society Regulatory Focus journal, and by the Japanese Federation of Medical Devices Association.
• Surveying the Medical Device Development Community: HBD and the University of Tokyo conducted a survey asking several Japan, U.S., and E.U. based-medical device manufacturers about the costs of medical device clinical trials. This helped uncover common challenges in bringing innovative and safe device technologies to patients.