Lessons Learned Through HBD: The Regulator’s View - US FDA Melissa Torres, ME, MS Associate Director for International Affairs Office of the Center Director Center for Devices and Radiological Health

  I, Melissa Torres, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

Mechanisms of Global Harmonization Harmonization by Doing (HBD) Japan and US collaboration International Medical Device Regulators Forum (IMDRF) Australia, Brazil, Canada, China, Europe, Japan, Russia, Singapore, and US Sharing of non-public information between Regulators

Harmonization by Doing Use of internationally agreed upon standards for global clinical trials for cardiovascular devices. Developed by US and Japanese regulators, academia, and industry in order to promote timely medical device approvals in both countries.

Advantages of Global Clinical Trials Facilitates more timely and cost-effective evaluation/introduction of new products in multiple countries Reduction of redundancies in time and cost Simultaneous international enrollment Ability to pool patients may reduce the total number of patients needed compared to running separate trials Ability to collect more comprehensive data based on differences in patient populations and clinical practice

Global Clinical Trial Challenges Poolability of patient data Demographics Clinical practice patterns Differences in trial infrastructure and regulations Site recruitment Monitoring Cost per patient

Why the US and Japan? Large markets Strict regulatory systems Comparable levels of clinical care Close regulatory partners with a history of successful collaborations

CDRH Initiatives and HBD In recent years, FDA’s Center for Devices and Radiological Health (CDRH) has focused on increasing medical device innovation to benefit the public: Greater initiation and utility of clinical trials Greater efforts related to the use of patient registries and real world evidence both in the US and globally Improved use of benefit-risk principles HBD activities continue to support CDRH’s initiatives through development of: Single-protocol, international clinical studies Standardization activities

CDRH’s Activities Moving Forward Increased use of “real-world” clinical data Registries Other clinical experience outside of formal studies Greater acceptance of international clinical data Pre-market studies These efforts are in line with spirit of HBD

Additional Related International Efforts Patient Registries – IMDRF Work Item Goal Develop shared essential principles of informatics infrastructure and best epidemiologic and statistical analytic methodologies to enhance the quality, speed and cost-efficiencies of regulatory science for medical devices. Documents Principles of International System of Registries Linked to Other Data Sources and Tools Essential Methodological Principles in the Use of International Medical Device Registry Data New Work Item Proposal IMDRF Registry Qualification Tool IMDRF Real-World Evidence essential principles document and a catalogue of existing RWE efforts Registries of patients undergoing medical device procedures represent a growing potential electronic resource for local and global medical device evaluation and tracking.

Next Steps? The success in collaboration and outreach among regulatory, academic, and industry stakeholders to promote global clinical studies through HBD is helping to facilitate evaluation and availability of safe, effective, and innovative cardiovascular devices. Where do we go from here? Further promotion of the program Expansion to other product areas Additional proposals and participation

Summary CDRH is strongly supportive of global clinical evaluation efforts as they are in line with many of our strategic initiatives. Sharing information and working in partnerships globally to address issues of mutual interest and concern ultimately allows patients timely access to safe, effective, and high-quality medical devices. HBD, IMDRF, APEC RHSC, etc.

Thank You