Overview
ISO 10993-4:2017/Amd 1:2025 is the latest amendment to the international standard for the biological evaluation of medical devices, specifically focusing on the selection of tests for interactions with blood. This amendment updates and clarifies protocols essential for assessing haemocompatibility-how medical devices interact safely and effectively with blood. Developed by ISO/TC 194 in collaboration with CEN/TC 206, the standard guides manufacturers and regulators in selecting appropriate testing methods to ensure device safety and performance in contact with blood.
Key Topics
- Test Selection for Blood Interaction: The amendment refines criteria for choosing haemocompatibility tests based on device contact type-direct or indirect blood contact-and device category.
- Device Categorization: Updates include detailed classifications such as external communicating devices (both direct and indirect blood contact), implant devices, and blood administration sets, helping stakeholders determine specific test requirements.
- Haemocompatibility Testing Methods: It differentiates between direct contact tests (e.g., direct haemolysis, coagulation, complement activation) and extract-based or indirect tests, emphasizing that surface contact is key for many haemocompatibility responses.
- Consideration of Antithrombotics: Guidance on evaluating devices in presence or absence of antithrombotic agents is provided, highlighting the need to justify their use depending on clinical scenarios and species differences.
- Updated Terminology and References: For example, the update replaces “ISO/TR 10993-20” with “ISO/TS 10993-20” and adds new bibliographic references related to state-of-the-art in vitro thrombogenicity testing.
- Device-Specific Test Matrix: The amendment revises Table 1 outlining appropriate test categories-such as thrombosis, haemolysis, platelet activation-for various devices, from catheters to prosthetic vascular grafts, ensuring tailored evaluation pathways.
- Clarifications on Test Article Selection: Only components with blood contact (direct or indirect) should be tested to minimize confounding factors, with justification required for exceptions.
Applications
ISO 10993-4:2017/Amd 1:2025 serves as a critical resource for multiple stakeholders involved in medical device development and regulation:
- Medical Device Manufacturers: Enables the selection of scientifically justified haemocompatibility tests tailored to device design and blood-contact type to comply with safety standards and regulatory submission requirements.
- Regulatory Bodies: Provides standardized criteria and test selection guidelines for device evaluation, facilitating consistent risk assessment and approval decisions for blood-contacting medical devices.
- Research and Development: Supports the innovation of blood-contacting devices such as catheters, blood monitors, extracorporeal systems, and vascular implants, by validating biocompatibility and haemocompatibility throughout product lifecycle.
- Testing Laboratories: Offers protocols for in vitro, ex vivo, and in vivo haemocompatibility assays, including considerations for anticoagulant use and surface-specific interactions, essential for accurate test design and reporting.
Related Standards
- ISO 10993 Series: This amendment complements Part 2 (Animal Welfare Requirements), Part 6 (Tests for Local Effects after Implantation), and Part 20 (Immunotoxicology Testing), providing a comprehensive framework for biological evaluation of medical devices.
- ISO/TS 10993-20: Principles and methods for immunotoxicology testing of medical devices referenced for immune response evaluations related to haemocompatibility.
- ISO 18242 & ISO 18193: These standards on cardiovascular implants and cannulae for extracorporeal circulation provide additional technical requirements relevant to blood-contacting devices.
- ASTM F2888: A testing standard for platelet and leukocyte count assays, referenced for thrombogenicity screening of biomaterials used in blood-contacting devices.
By adhering to the updated ISO 10993-4:2017/Amd 1:2025, stakeholders ensure rigorous evaluation of blood interactions, enhancing patient safety and device efficacy in clinical applications involving direct or indirect blood contact. This amendment reflects the latest scientific insights and regulatory expectations in haemocompatibility assessment.
Open preview (PDF)Biological evaluation of medical devices — Part 4: Selection of tests for interactions with blood — Amendment 1
