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

AbstractTo dateblood 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 performanceWhile ISOidentifies five categories of responses that should be consideredthrombosiscoagulationplateletsleukocyte activationand complementthe scientific and regulatory communities continue to focus on coagulation and plateletsThe other ISO categories dealing with inflammation are typically dealt with early and separately as part of biomaterial developmentThis current approach all but guarantees missing interactions of coagulation and inflammation necessary to predict in vivo performanceCurrent testing methodologies also fail to evaluate the categorical responses under physiological limits of the key Virchow variables of blood flowcondition of the bloode gcoagulopathiesand the influence of the blood contacting surfaceThese uncertainties and the current cost of comprehensive testing stifle development of new materials or surface coatingsIn factthe FDA has repeatedly acknowledged these shortcomings and encouraged development of new test methods and formulated the Medical Device Development ToolMDDTprogram to address this matterEnsion proposes development of a systemEnsion Triad System or ETSto provide effective positive and negative control ranges for each of the Virchow variablesETS will enable designed experiments capable of generating quantitative analysis of variance and identify conditions for optimal performance in all five ISO categoriesEnsion 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 protocolsThis Phase II project represents the main research and development for ETS with the endgoal to submit to FDA s MDDT program for system qualificationIn Specific Aimwe will refine the Phase I ETS design for manufacturabilityconduct GMP based fabrication of ETS systems in sufficient quantities to support the needs of Specific Aimand Specific AimIn Specific AimETS systems without test articles will be used to characterize the confidence interval of the responses of the five ISOcategories as a function of the key Virchow independent variablesFinallyin Specific AimETS 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 Project NarrativeCurrent in vitro systems and methods to assess blood compatibility of biomaterials and medical products have been unable to achieve a comprehensive understanding of the blood biomaterial interaction to predict in vivo performanceThis Phase II proposes the main research and development effort of a standardizedcost effectivebench top blood circulation loop and accompanying testing protocols that can comprehensively address all five categories of blood compatibility and account for each Virchow variable in a singlehighly controlled test