System and comprehensive approach for blood compatibility of medical devices and biomaterial

Ension, Inc., Pittsburgh PA

Investigators

Abstract

Abstract ?To date, blood compatibility testing of biomaterials and medical devices has not led to a consensus on what materials are non-thrombogenic nor has it advanced understanding of what and how variables and responses can be measured in vitro to begin to predict in vivo performance. While ISO 10993-4 identifies five categories of responses that should be considered (thrombosis, coagulation, platelets, leukocyte activation, and complement), the scientific and regulatory communities continue to focus on coagulation and platelets. The other ISO categories dealing with inflammation are typically dealt with early and separately as part of biomaterial development. This current approach all but guarantees missing interactions of coagulation and inflammation necessary to predict in vivo performance. Current testing methodologies also fail to evaluate the categorical responses under physiological limits of the key Virchow variables of blood flow, condition of the blood (e.g., coagulopathies), and the influence of the blood contacting surface. These uncertainties and the current cost of comprehensive testing stifle development of new materials or surface coatings. In fact, the FDA has repeatedly acknowledged these shortcomings and encouraged development of new test methods and formulated the Medical Device Development Tool (MDDT) program to address this matter. Ension proposes development of a system (Ension Triad System or ETS) to provide effective positive and negative control ranges for each of the Virchow variables. ETS will enable designed experiments capable of generating quantitative analysis of variance and identify conditions for optimal performance in all five ISO categories. Ension developed and demonstrated the feasibility of the ETS system in our Phase I activities demonstrating statistically significant categorical responses that identify known clinical mediators not revealed in current testing protocols. This Phase II project represents the main research and development for ETS with the end- goal to submit to FDA?s MDDT program for system qualification. In Specific Aim 1 we will refine the Phase I ETS design for manufacturability, conduct GMP-based fabrication of ETS systems in sufficient quantities to support the needs of Specific Aim 2 and Specific Aim 3. In Specific Aim 2, ETS systems without test articles will be used to characterize the confidence interval of the responses of the five ISO 10993 categories as a function of the key Virchow independent variables. Finally, in Specific Aim 3 ETS systems will be evaluated in human blood using prototype catheters as test articles and data will be compared with current ISO categorial blood compatibility evaluations.