ISO 10993-4:2017

Overview

ISO 10993-4:2017 - Biological evaluation of medical devices - Part 4: Selection of tests for interactions with blood provides general requirements and guidance for assessing how medical devices interact with blood. It defines a device classification scheme (based on ISO 10993-1), outlines fundamental principles for evaluating blood contact, and gives the scientific rationale for selecting structured test strategies. The standard emphasizes that detailed, device‑specific test methods are outside its scope and that prior compliant testing remains valid.

Key topics and technical requirements

• Device classification: Categorizes devices by intended use and duration of blood contact (non-blood-contact, external communicating, implant devices) following ISO 10993-1.
• Principles of blood interaction evaluation: Focus on risk-based selection of tests informed by device design, materials, clinical use and exposure.
• Target biological endpoints: Guidance covers thrombosis, haemolysis, platelet and leukocyte activation, and complement activation as contributors to haemocompatibility issues.
• Types of test approaches: Describes in vitro, ex vivo, and in vivo test categories and when each is appropriate.
• Annex material: Informative annexes explain preclinical evaluation of cardiovascular devices (Annex A), commonly recommended laboratory tests and their scientific basis (Annex B), in vivo thrombosis methods (Annex C), haemolysis/haematology (Annex D), complement testing (Annex E), less common tests (Annex F) and tests not recommended (Annex G).
• Limitations: Acknowledges current limits in test precision and knowledge - the document provides high‑level guidance rather than prescriptive test parameters.

Applications and who uses this standard

ISO 10993-4:2017 is used by:

• Medical device manufacturers and R&D teams designing blood-contacting components (e.g., catheters, vascular grafts, extracorporeal circuits).
• Regulatory affairs and quality assurance professionals preparing biological evaluation files and preclinical evidence.
• Preclinical laboratories selecting appropriate haemocompatibility assays (in vitro thrombin generation, haemolysis screening, complement activation assays) and ex vivo/in vivo models.
• Notified bodies, regulators and clinicians reviewing safety data for devices that contact blood.

Practical uses include selecting an appropriate test matrix based on device classification, documenting rationale for chosen assays in risk management, and interpreting haemocompatibility data in the context of clinical risk.

Related standards

• ISO 10993-1 - Biological evaluation within a risk management process (primary classification and framework).
• ISO 10993-12 - Sample preparation and reference materials for biological testing.

Keywords: ISO 10993-4:2017, haemocompatibility, blood interactions, biological evaluation, medical devices, thrombosis, haemolysis, complement activation, in vitro testing, in vivo testing.