Introduction of New Technology: An FDA Division of Cardiovascular Devices Perspective Bram Zuckerman, MD, FACC Director, FDA Division of Cardiovascular Devices Office of Device Evaluation Center for Devices and Radiological Health

I/we have no real or apparent conflicts of interest to report. Bram D. Zuckerman, MD I/we have no real or apparent conflicts of interest to report.

CDRH Challenges Assure the safety and effectiveness of medical devices through the use of appropriately rigorous scientific evaluation despite the fact that: Science is continually evolving Devices are becoming increasingly more complex Existing regulatory pathways to market were initially established in 1976 Promote device innovation to bring important public health benefits to patients safely and quickly 4

CDRH Innovation Initiative CDRH Medical Device Innovation Initiative Website (http://www.fda.gov/AboutFDA/Innovation/default.htm) Facilitate the development and regulatory evaluation of innovative medical devices Strengthen the U.S. research infrastructure and promote high-quality regulatory science Prepare for and respond to transformative innovative technologies and scientific breakthroughs

Effective Use of Early Interaction Early interaction with FDA is a key to addressing and resolving issues Need to address FDA concerns that are raised in Pre-submission discussions Sufficient safety evidence is needed to begin clinical studies in U.S. – most disapprovals based on inadequate bench and/or animal testing

What is the Current Landscape of Medical Device Development? FDA acknowledges real or perceived problems: Initial clinical testing of novel devices has moved to non-US sites Device innovation may follow overseas Devices are being exclusively developed for non-US markets FDA’s requirements can be an impediment to early clinical testing of new devices Growing concern regarding the time lag in the availability of beneficial medical devices for US patients

Climate Change at FDA CDRH priorities include: Encouraging medical device innovation Enhancing regulatory science Facilitating clinical studies in the US.

Words into Deeds The core principle in meeting these priorities is the application of benefit/risk principles throughout regulatory decision-making Benefit/Risk Guidance Identifies the factors that can be used in making benefit/risk determinations during premarket review The Innovation Program Priority review program for innovative devices with promising and potentially far reaching benefits Entrepreneurs-in-Residence Program to enhance regulatory science Early Feasibility Study Guidance Use of benefit/risk principles to justify study initiation

Benefit-Risk Principles Allow regulators to: Consider the totality of the benefit/risk profile for the device, for example: Disease condition (e.g., life-limiting, life-threatening) Limitations of and risks associated with currently available therapies Consider patient tolerance for risk and perspective on benefits Severity and chronicity of disease Availability of alternative treatments/diagnostic modalities Take into account risk mitigation strategies when balancing risks and benefits http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm267829.htm

Early Feasibility Study (EFS) Guidance Intended to facilitate the clinical evaluation of medical devices in the US under the Investigational Device Exemptions (IDE) regulations Elements that define an early feasibility study: Small number of subjects (generally fewer than 10 initial subjects) Device intended for a specific indication that may be early in development, typically before the device design has been finalized Does not necessarily involve the first clinical use of a device Start at the bottom

Key Principles for Approval of an Early Feasibility Study For some new devices, exhaustive nonclinical testing would not likely provide the information needed to further device development In these cases, early clinical use of the device in a limited number of subjects is needed to: provide initial insights into clinical safety and device function; inform subsequent clinical and non-clinical testing; and/or improve device performance through iteration before finalizing the design Approval of an early feasibility study IDE may be based on less nonclinical data An EFS must be supported by an appropriate benefit/risk analysis, including justification for the types and amount of data need to support study initiation.

Summary FDA recognizes the public health benefits of encouraging medical device innovation in the US Facilitating device innovation and identifying ways to improve the clinical trials ecosystem are CDRH priorities, involving new approaches and philosophies