Thrombogenicity Testing for Blood-Contacting Medical Devices in an In Vitro Ovine Blood Loop: Design Improvements and Continuing Validation

Abstract

Thrombogenicity testing is often a requirement for regulatory approval of many types of blood-contacting medical devices [1, 2]. This study describes the continuing improvement in design and characterization of a minimally-heparinized in vitro blood-loop assay which utilizes freshly drawn ovine blood. These modifications were made after studies using this in vitro model were submitted to the FDA in lieu of the in vivo nonanticoagulated venous implant (NAVI) thrombogenicity test. After extensive discussions with FDA reviewers, several modifications which further characterize and improve the assay have been included: 1). Improved temperature control of the blood before and during the incubation period, 2). Improved uniformity and reproducibility of loop geometry, specifically the length of working space for device deployment and a fixed curvature for the radius of the return segment of the loop, 3). Additional measurement of blood parameters prior to and during the incubation period, complete blood counts and activated clotting time (ACT), 4). More rigorous management of ACT, 5). Measurement of non-adherent thrombus formation in the blood, 6).Incorporation of a legally marketed predicate comparator device in all the assays, and 7).Physical characterization of the positive controls. This validated method with enhanced characterization and more reproducible methods allows for a more robust and reliable assay. These results continue to support the premise that this in vitro blood loop assay may eventually supplant the NAVI model for routine hemocompatibility testing for catheter-like blood contacting medical devices.