1. Balancing Regulation and Innovation: 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

2. 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.

3. 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

4. CDRH Innovation Initiative
CDRH Medical Device Innovation Initiative Website (
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

5. 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

6. 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

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

8. 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

9. 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

10. 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

11. 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.

12. 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