1. 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

2. 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.

3. 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

4. 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.

5. 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

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

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

8. 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

9. 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

10. 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.

11. 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

12. 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.

13. Thank You