Novel Devices Focus—The Path Forward for New DES, DEB, and Biodegradable Stents: FDA View Hina M. Pinto, MSE Scientific Reviewer Interventional Cardiology Devices Branch Division of Cardiovascular Devices Office of Device Evaluation CDRH/FDA CRT 2010 Washington, D.C. February 23, 2010

Hina M. Pinto DISCLOSURES I have no real or apparent conflicts of interest to report.

Overview New Drug Eluting Stents (DES) Drug Eluting Balloons (DEB) DES Guidance document Different considerations Drug Eluting Balloons (DEB) Pre-clinical bench testing Animal testing Clinical considerations Biodegradable Stents Challenges Testing Conclusions

New Drug Eluting Stents DES Guidance currently in draft at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072193.pdf Many of the current recommendations would apply to new DES. Certain modifications and additional testing may be recommended for novel devices based on indication and design.

New Drug Eluting Stents Different considerations for novel devices Dedicated Bifurcation DES Modified bench testing Accelerated durability testing Particulates testing Appropriate animal study model Identify appropriate trial design (e.g., control) Different materials (e.g., Nitinol) Surface characterization Nickel leaching Fracture due to overlapping of dissimilar materials New Coatings (e.g., antibody coated stents, biologics) Textured Coatings

Drug Eluting Balloons Some of the challenges are the same as DES Local drug delivery and associated toxicities Effects on healing as observed in the animal studies Pre-clinical Testing Characterization of finished, sterilized product to be studied essential Coating/drug loading characteristics for different balloon sizes Particulates and Coating Integrity Concern about particulate generation on deployment Simulated use testing condition recommended Identification of Particulates Additional to support other indications (e.g., ISR, small vessels) Animal Studies to assess Safety Safety/healing related to drug toxicity Safety margin overdose

Drug Eluting Balloons Animal Studies to assess Effectiveness Neointimal proliferation Proof of principle vs. PTCA or stent control Clinical Data Potential use of multiple balloons Higher dose to patient Although drug is rapidly delivered acutely, the drug can remain in the tissue longer and could result in delayed healing. Therefore, we have recommended 180-day animal studies to understand the time course for healing Animal studies: 3-5d, 30d, 90d, 180d follow-up Recommend 9-month clinical data to understand whether effectiveness is maintained over time.

Biodegradable Stents—Challenges Apply also to durable stent platforms with biodegradable coatings Answers to these questions will guide the testing paradigm: What is the expected degradation profile? What are the degradation products? What are the expected advantages of this degradable stent? How does the proposed stent design balance the need for mechanical integrity following deployment with the ability to degrade over time?

Biodegradable Stents—Testing Challenges in Characterization Degradation profile Mechanism Characterization of intermediate breakdown products Characterization of polymer Bench Testing Considerations Mechanical properties (e.g., radial stiffness, radial strength) Particulates testing challenges when stent and/or polymer degrade Coating integrity Accelerated durability testing Need to conduct mechanical tests at multiple time points (in a physiologically relevant environment) to fully characterize the impact of degradation on mechanical integrity.

Biodegradable Stents—Testing Animal Studies Measurement time points may need to be modified to better capture critical safety parameters Safety and Effectiveness evaluation Assessment of downstream myocardial pathology critical Evaluate embolization due to bulk degradation Biologic effects of degradation products

Biodegradable Stents—Testing Clinical Study Duration of patient follow-up reflects degradation profile To adequately capture outcomes before, during, and after stent degradation Follow-up imaging to confirm degradation (IVUS, OCT) Evaluate visibility on fluoroscopy Assess frequency of geographic miss Ability to accurately deploy overlapping stents in bailout situations Assess DAPT use and optimal duration

Conclusions Lessons learned from DES and draft guidance can provide a starting point for evaluation of novel DES, DEB, and biodegradable DES. FDA takes into consideration specific features of each to recommend appropriate modifications to key elements of nonclinical and clinical testing. FDA has multiple mechanisms for interactions – formal and informal. We encourage interactions early and often to identify appropriate clinical and pre-clinical considerations.

Thank You! Hina M. Pinto Interventional Cardiology Devices Branch hina.pinto@fda.hhs.gov Ashley Boam Chief, Interventional Cardiology Devices Branch ashley.boam@fda.hhs.gov Combination products combination@fda.gov