EN ISO 10993-4:2017/A1:2025 PDF

Overview

EN ISO 10993-4:2017/A1:2025 is the CEN-endorsed amendment to ISO 10993‑4 (Part 4 of the ISO 10993 series) that updates guidance for the biological evaluation of medical devices with respect to interactions with blood. Published February/April 2025 and approved by CEN, this amendment clarifies device categories, refines test selection for haemocompatibility, and aligns testing practice with risk management and EU regulatory expectations (see Annex ZA relating to Regulation (EU) 2017/745).

Key topics and requirements

• Scope focus: Guidance is specific to selection of tests for device parts that have direct or indirect contact with blood (surface-contact dependent tests vs. extract-based tests).
• Test types identified: Direct and extract-based haemocompatibility assessments including direct haemolysis, indirect haemolysis, complement activation, coagulation, platelet activation, haematology, and in vitro/ex vivo thrombosis.
• Test article selection:
  • For direct-contact haemocompatibility tests, only the direct blood-contacting components should be tested to avoid interference from non-contacting parts.
  • For extract-based tests, both direct and indirect blood-contacting components should be considered.
• Device categorization updates: The amendment adjusts examples and categories - e.g., adds blood monitors with indirect blood contact, reinserts blood collection devices, cannulae, cell savers, and clarifies storage/administration devices as those for saline and/or therapeutics (previously referenced as blood and blood products).
• Manufacturing/process changes: NOTE updated to emphasize that changes in manufacturing, suppliers or manufacturing aids that alter surface properties or chemistry can affect haemocompatibility and may require re-evaluation.
• Updated Table 1: The table mapping device types to appropriate haemocompatibility test categories has been revised (see standard for details).

Practical applications and users

This amendment is essential for:

• Medical device manufacturers designing or changing devices/components that contact blood (catheters, cannulae, blood-contacting sensors, tubing, infusion sets).
• Regulatory and quality teams preparing technical documentation and claiming conformity with EU MDR (Regulation (EU) 2017/745) where this harmonized standard is applied.
• Test laboratories and contract research organizations (CROs) performing haemocompatibility testing and advising on test article selection and sample preparation.
• Notified bodies and clinical evaluators assessing biological safety evidence for devices with blood contact.

Related standards

• ISO 10993‑1:2018 (EN ISO 10993‑1:2020) - biological evaluation within a risk management process.
• ISO 10993‑12:2021 (EN ISO 10993‑12:2021) - sample preparation and reference materials.

For implementation details, test procedures and the revised Table 1, consult the full text of EN ISO 10993‑4:2017/A1:2025 and the referenced ISO 10993 parts.