Pinhas (Peter) Dartal 01 June QA role in development of Percutaneous Aortic Valve prosthesis

Transcatheter Heart Valve Prosthesis Tested to ISO5840 and FDA surgical Heart Valve Guidance In-vitro durability simulating 5 years (200 million cycles) Frame fatigue testing simulating 15 years (600 million cycles)

Regulatory requirements Medical device field is highly regulated so even the most brilliant new medical devices are of no value, if needed approvals from relevant authorities are not secured. Quality assurance and regulatory affairs departments play a major role in getting the required approvals.

Regulatory requirements In the United States all devices in commercial distribution are classified in class I, II, or III, depending on the degree or regulation necessary for the reasonable assurance of safety and effectiveness of the device.

Regulatory requirements Premarket notification- 510(K) is required by FDA in order to establish substantial equivalence in safety and effectiveness to a medical device already marketed in the United States.

Regulatory requirements Premarket Approval Application (PMA) is required by FDA for class III devices and is, in effect a private license granted for marketing a particular medical device.

Regulatory requirements An Investigational Device Exemption (IDE) is permission from clinical authorities to conduct clinical studies on human subjects about a new device, or a new intended use or modification for an existing device.

Regulatory requirements In Europe all devices in commercial distribution are classified in class I, IIa, IIb, or III, and require Conformité Européenne, "European conformity" (CE) marking for commercial distribution, to be issued by a Notified Body.

Aortic stenosis Aortic stenosis may begin as a result of infection, rheumatic fever or a congenital abnormality. Typically, the valve tissue becomes scarred, inflamed or thickened. Calcium may collect on the valve, reducing the flexibility of the valve leaflets As the valve leaflets lose their flexibility, the area through which blood flows is reduced. As it becomes harder to push blood through the valve, the muscles of the heart chamber wall stretch and thicken, leading to an increased likelihood of heart failure.

Medical device companies Majority of employees are engineers Number of M.D’s is very small (if at all)

QA role in development Design Controls – framework that must be used for devices development and for understanding the intent of regulation Design and Development Planning Design Input Design Output Design Review

QA role in development Design Verification Design Validation Design Transfer Design Changes Design History File QA is involved in all projects

THV The Transcatheter Heart Valve (THV), is a prosthetic device intended for use for patients who suffer from Severe Aortic Valve Stenosis. It is an artificial heart valve designed for a less invasive implantation by transluminal catheter technique without thoracotomy and open-heart surgery.

Balloon expandable Stainless Steel or Cobalt Chromium frame:  Consistency & durability with non-conformable, Radial strength for concentric shape that creates uniform stress on leaflets and limits contact with frame  symmetrical, discreet frame –Radial strength for concentric shape that creates uniform stress on leaflets and limits contact with frame  Consistency & durability with non-conformable, symmetrical, discreet frame –Radial strength for concentric shape that creates uniform stress on leaflets and limits contact with frame

Bovine pericardial leaflets: Matched for deflection and thickness for optimal coaptation and durable hemodynamic performances

Crimper

Delivery system

One Valve with Two Complementary Approaches One Valve with Two Complementary Approaches Transapical Delivery System Transfemoral Delivery System

Edwards SAPIEN™ THV using the RetroFlex 3™ Transfemoral Delivery System

Edwards SAPIEN™ THV using the Ascendra™ Transapical Delivery System