in-vitro testing

How APS Strives to Improve Biocompatibility Testing: In-Vitro Blood Loop Assay

Thrombogenicity testing is a requirement for regulatory approval of blood-contacting medical devices. Although in-vivo assessments, typically the non-anticoagulated venous implant (NAVI) model, are often part of submission packages, acute thrombogenicity assessments in animals for catheters and catheter-like devices continue to be problematic in many of these testing schemes. These problems include the position of the devices in the animal anatomy, implantation technique, device contact with the vein wall, expertise of the performing laboratory and the overall limited statistical power of the study designs. As medical devices continue to become more complex with the integration of electronic systems and more diverse materials, the clinical relevance and overall placement of the device pose challenges to the traditional in-vivo thrombogenicity assessment.

Currently there are initiatives within the FDA and other regulatory authorities for expanding the efforts to develop alternative validated in vitro models. There is a history of use with in vitro blood loop models in the assessment of thrombogenicity for cardiovascular devices that can be utilized at the time of device design, material selection and/or surface optimization to replace the less dependable in-vivo models. The key characteristics of successful in vitro models include the use of freshly drawn blood, low levels of anticoagulants, dynamic flow conditions with shear stress, and minimization of air/blood interfaces. The APS In-Vitro Blood Loop integrates freshly collected ovine or human blood containing minimal levels of heparin (target concentration 1.0 IU/ml) with unidirectional flow in an enclosed loop driven by a peristaltic pump. The pump and tubing (inside diameter: 0.375 inch) are those commonly used in heart-lung bypass systems and are therefore ideally suited to blood flow with minimal potential for impacting any aspects of the coagulation pathway. Control materials have been selected to reproducibly elicit positive and negative or neutral thrombogenic responses.