Regulatory Considerations for Coronary Drug Coated Balloons FDA

Regulatory Considerations for Coronary Drug Coated Balloons – FDA View Hina M. Pinto, MSE Interventional Cardiology Devices Branch Division of Cardiovascular Devices Office of Device Evaluation CDRH/FDA CRT 2011, Washington, D. C. March 1, 2011

Disclosure Information No conflict of interest to report.

Drug-Coated Balloons (DCBs) Hybrid technology – PTCA balloon + drug = Combination product Regulated with CDRH as the lead center, with consultation to CDER – Primary mode of action is balloon dilatation of vessel Class III/PMA

DCB Challenges Balance amount of drug for effectiveness vs. acceptable safety profile – Local drug delivery and associated toxicities – Evaluate loss of drug during delivery (e. g. , tracking) Evaluate effects on safety & healing of the vessel (initially through the animal studies) Determine the potential for larger drug doses in vivo with use of DCB (e. g. , higher arterial tissue concentration) Assess the potential for larger doses of drug to be released into bloodstream when DCB is inflated (vs. remain on DES)

DCB Pre-Clinical Testing Bench testing – Adequate characterization of the coating and balloon Animal Studies to assess safety – – – Drug toxicity Amount of time the drug stays in arterial wall Delayed, incomplete healing Adequate characterization of how long the drug is in tissue will affect device evaluation and testing. Complete characterization and testing is necessary even if the drug has been used for other indications (e. g. , DES) Adequate bench and animal studies to assess safety prior to human studies

DCB Clinical Considerations Proposed Indication – – ISR de novo small vessels bifurcation lesions Well-defined patient population – Based on DCB design and indication Potential for multiple inflations of the DCB Potential for the use of multiple DCBs clinically – Higher drug dose to patient Although drug is rapidly delivered (acutely), the drug can remain in the tissue longer and could result in delayed healing.

DCB Clinical Considerations Robust trial design (RCT) – Superiority or non-inferiority – Choice of control (e. g. , approved DES) Primary endpoint evaluation – Target lesion failure (TLF) rate – At least 9 month evaluation for ISR; (possibly 12 month for small vessels, bifurcations, etc. ) Longer term follow-up for DCB will likely be recommended. – Need to understand any long-term effects, potential for ST, and implications of recommended DAPT – FDA encourages you to discuss follow-up duration with us on an individual basis Details of study design depend on clinical indication and DCB design.

DCB Summary DCBs bring their own challenges in both science and regulation. – DCBs are not DES; DCBs are not PTCA catheters either. – Not permanent implants, but as the drug can form a depot in the tissue and be present beyond the in-hospital time period, healing and longer-term outcomes are important (vs. just acute). Adequate characterization of the DCB will inform preclinical and clinical recommendations. We encourage interactions early and often to identify appropriate pre-clinical considerations and clinical trial design. – IDEs often delayed due to preclinical issues (not clinical trial design concerns), so early interaction is critical.

Thank You. Hina M. Pinto (301) 796 -6351 hina. pinto@fda. hhs. gov Draft Coronary DES Guidance http: //www. fda. gov/downloads/Drugs/Guidance. Compliance. Reg ulatory. Information/Guidances/UCM 072193. pdf Class II Special Controls Guidance for PTCA Catheters http: //www. fda. gov/Medical. Devices/Device. Regulationand. Guida nce/Guidance. Documents/ucm 225145. htm