The FDA Early Feasibility Study Pilot and the Innovation Pathway Andrew Farb, MD and Dorothy Abel, BSBME Division of Cardiovascular Devices Center for Devices and Radiological Health (CDRH) andrew.farb@fda.hhs.gov Medical Device Innovation 2013: The FDA Town Hall CRT 2013 Washington, DC February 26, 2013

I/we have no real or apparent conflicts of interest to report. Andrew Farb, MD I/we have no real or apparent conflicts of interest to report.

Climate Change at FDA FDA recognizes: Advantages for the device development process with US clinical studies (including FIH and early feasibility studies) Opportunity for close contact between developers & investigators Early access to promising novel technology Continuity of clinical investigations Human costs associated with delaying access to new technology, in the context of the limitations of current treatment alternatives A need for a cultural change to shift the focus from not only protecting public health but also to promoting public health

Words into Deeds The core principle in meeting these priorities is the application of benefit/risk principles throughout regulatory decision-making 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 Patient tolerance for risk & perspective on benefits Risk mitigation strategies when balancing risks and benefits

The Innovation Pathway Priority review program launched February 2011 intended to: Shorten the total time to market Transform the FDA/innovator experience Targeted for pioneering technologies that address unmet clinical needs and have the potential to revolutionize patient care or health care delivery Early and intensive investment of resources Sponsor/FDA collaboration early in the device development process to identify the appropriate and least burdensome pathway to market

End Stage Renal Disease Innovation Challenge Innovation Pathway 2.0: End Stage Renal Disease Innovation Challenge (32 Applications Received, 3 Chosen) UCSF bioimplantable artificial kidney CreatiVasc Hemoaccess Valve System BPTi Wearable artificial kidney

Entrepreneurs-In-Residence (EIR) Program Recruitment of entrepreneurs and innovators working with government employees Time-limited (6 months) participation Intended to deliver transformational change via principles of lean engineering in rapidly testing, validating and scaling new approaches

Current EIR Projects at CDRH Streamlining clinical trials: Find ways to reduce the time and cost of clinical trials in support of FDA approval or clearance of medical devices Streamlining the FDA approval-to-CMS coverage pathway: Find ways to reduce the inefficiencies and delays in data collection to support FDA approval and CMS coverage Striking the right balance between pre- and post-market evidentiary requirements: Find ways to allow efficient use of pre-market studies to allow for timely approvals, with greater emphasis on capturing informative real-world data in post-market studies

EFS Pilot Program Pilot program of 8 innovative device technologies is underway to implement and evaluate the draft EFS guidance Purpose of the Pilot Identify strengths and weaknesses of the guidance document Assess whether adequate guidance is provided toward targeting IDE approval Status of the Pilot Pre-IDE and IDE FDA/sponsor interactions are ongoing FDA Based on feedback from pilot, the guidance has been modified to: Improve the device evaluation strategy section; Provide additional guidance on preparing the informed consent form for an EFS; and Emphasize benefit/risk principles. Sponsor

FDA EFS Guidance Revisions Based on Pilot Experience and Comments Emphasized benefit/risk concepts throughout the document Improved the Report of Prior Investigations section to clarify the information that will be useful to justify study initiation Expanded on the Device Evaluation Strategy Included device design information and clinical protocol risk mitigation strategies in the table to provide the appropriate context when considering benefit/risk Added a Design Control section Included more guidance on drafting the informed consent form for an EFS Suggested pre-submission topics for discussion between the sponsor and FDA

FDA EFS Guidance Update Although new pilot projects are not being accepted, EFS IDEs may be submitted prior to the publication of the final guidance. Many sponsors have committed to conducting EFS studies in the US. Publication is anticipated soon.

Parting Thoughts Early and continuous interaction between FDA and sponsors will be instrumental in FDA’s efforts to facilitate innovation Accelerating innovation involves getting to the answers quicker and not just shortening the time to market or reducing regulatory requirements

Contacts Early Feasibility Study Guidance Innovation Pathway Dorothy.Abel@fda.hhs.gov Andrew.Farb@fda.hhs.gov Innovation Pathway Murray.Sheldon@fda.hhs.gov Associate Director for Technology & Innovation, CDRH