Medical devices that contact blood are required to demonstrate hemocompatibility to ensure patient safety. Applicable testing requirements, however, can vary significantly depending on device type, intended application, patient population, and nature of contact between the device and patient blood, which can be indirect (e.g., infusion pumps), direct (e.g., catheters, heart valves), or extracorporeal (e.g., dialysis systems). While ISO 10993-4 describes the requirements for assessing the interactions of medical devices with human blood, the US Food and Drug Administration (US FDA), American Society for Testing and Materials (ASTM), and the Organisation for Economic Co-operation and Development (OECD) also publish guidelines and standards on blood compatibility testing that may be relevant to your device. The hemocompatibility experts at Gradient can guide you through the hemocompatibility testing process, from understanding applicable safety and regulatory requirements to designing an appropriate hemocompatibility evaluation plan for market approval. Our scientists have backgrounds in immunotoxicology, chemistry, molecular toxicology, and medical device risk assessment, with extensive experience in hemolysis, thrombosis, and immunology testing.
Gradient’s scientists are experts in developing biocompatibility testing approaches and achieving US FDA and EU MDR regulatory approval via different application paths. We can design, interpret, and troubleshoot studies conducted in accordance with ISO 10993-4, US FDA guidance documents, relevant ASTM standards, OECD Test Guidelines, and device-specific regulatory feedback. Gradient’s expertise and specialized knowledge can help you navigate the unique testing considerations for your medical device in relation to predicate device selection, inclusion of appropriate controls, selection of static vs. dynamic test setups, use of human vs. animal blood, incorporation of whole blood vs. blood products (e.g., plasma), and identification of clinically relevant worst-case testing conditions.
Our Areas of Expertise Include:
In Vivo Evaluation of Medical Device Thrombogenicity Risk in a Large Animal GLP Study
Gradient collaborated with a clinical team to design and conduct large animal safety and efficacy studies (canine, swine) to demonstrate biocompatibility of a stent for regulatory submission. We helped develop an in vivo good laboratory practice (GLP) study to simultaneously address the ISO 10993 endpoints of implantation and hemocompatibility – efforts which significantly reduced both the number of animals required for testing and the overall cost to the client.
Testing Support for In Vitro Assessments of Thrombogenicity for an EU MDR Submission
Gradient interpreted the results of in vitro platelet and leukocyte (P&L) count and partial thromboplastin time (PTT) assays conducted with a blood ultrafiltration device. Gradient successfully justified the results for parameters with no explicit acceptance thresholds or criteria, and provided an expert opinion on the clinical implications of a borderline pass/fail result for one parameter.
Assessment of Metallic Leaching into Blood Products
Gradient developed and supported the execution of custom metallic leaching studies to demonstrate the rate and quantity of metallic leaching into blood and blood products. Gradient identified and justified worst-case testing conditions in consideration of operating temperature, device flow rate, device configuration, transfusion volume, and patient population. Gradient authored a custom protocol for the testing laboratory, and provided technical expertise to the client and laboratory to ensure the testing was executed appropriately.
Evaluation of Mechanical Hemolysis Induced by a Blood Delivery Device
Gradient provided technical expertise to assess mechanical hemolysis induced by a blood transfusion device. We developed a clinically relevant testing strategy, oversaw the execution of a feasibility study, and interpreted the results of the study. Gradient interacted with a regulatory agency to defend testing methodologies on behalf of the laboratory and client.
