Hemouyumluluk – ISO 10993-4

What Is Haemocompatibility — ISO 10993-4?

The haemocompatibility assessment examines the interaction of blood-contacting devices with blood components. ISO 10993-4 does not define a single test; it requires selecting suitable tests across five interaction categories (thrombosis, coagulation, platelets, haematology, and complement/immunology) according to how the device contacts blood.

Purpose of Haemocompatibility — ISO 10993-4

The purpose is to determine whether the device causes clot formation, destruction of red blood cells, or activation of the immune system. For blood-contacting devices, this endpoint is central to clinical safety.

Which Products Is Haemocompatibility — ISO 10993-4 Applied To?

Catheters and intravascular devices
Stents and grafts
Dialysis sets and oxygenators
Blood transfer sets and needles
Heart valves and support devices

In Which Sectors Is Haemocompatibility — ISO 10993-4 Used?

Medical DevicePharmaceuticalsHealthcareBiotechnology

Standards Related to Haemocompatibility — ISO 10993-4

ISO 10993-4evaluation of interaction with blood test

Haemocompatibility — ISO 10993-4 Conditions

Category selection: Relevant interaction categories are determined by the device's blood contact type and duration
Haemolysis: By direct contact and/or extract method
Coagulation and platelets: Clotting times and platelet count/activation
Complement: Measurement of complement activation markers

Equipment for Haemocompatibility — ISO 10993-4

Haematology analyser and coagulometer
Spectrophotometer (haemoglobin measurement)
ELISA reader (activation markers)
Blood circulation simulation rig (for dynamic tests)
Centrifuge and sample preparation equipment

Sample Requirements for Haemocompatibility — ISO 10993-4

The specimen must be supplied in its final state, having gone through all series-production processes (including sterilisation).
The surface area and mass of the device in patient contact must be provided.
Material composition, manufacturing aids and coating information, if any, must be shared.
The specimen quantity needed for extraction is calculated from the surface area; this must be confirmed before shipping.
Packaging integrity must be maintained for sterile products.

Duration of Haemocompatibility — ISO 10993-4

Tests such as haemolysis are completed within days. Thrombosis assessments requiring a dynamic circulation rig and studies covering the full category set span several weeks.

Haemocompatibility — ISO 10993-4 Procedure

1The device's blood contact type and duration are determined.
2The categories to be assessed are selected per ISO 10993-4.
3The specimen or extract is prepared.
4The selected tests are set up together with suitable controls.
5Changes in blood components are measured.
6Results are compared against the controls.
7Findings from the categories are combined in the biological evaluation report.

Haemocompatibility — ISO 10993-4 Acceptance Criteria

The acceptance criterion is selected from the relevant section of the standard according to the device's contact type (surface, externally communicating, implant), contact duration and intended use. The assessment relies not on a single test result but on the biological evaluation plan carried out under ISO 10993-1; this page therefore gives no fixed limit.

Evaluation of Results

The assessment relies on the full set of selected categories, not a single test result. Results are interpreted together with the anticoagulant therapy applied in the device's clinical use and the contact duration.

Haemocompatibility — ISO 10993-4 Report

Device identification, model and lot number, if any
Device contact type, duration and intended use
Standard and section applied
Extraction or sample preparation conditions
Cell line, test system or test rig used
Controls and their results
Observations, measurement results and assessment
A statement that the result applies only to the specimen submitted for testing

Accreditation

EUROLAB holds internationally recognised accreditation obtained from accreditation bodies party to the IAF and ILAC multilateral recognition arrangements, under ISO/IEC 17025 for laboratory testing, ISO/IEC 17020 for inspection and surveillance, and ISO/IEC 17021-1 and ISO/IEC 17065 for system and product certification. This chain ensures the reports and certificates issued are accepted worldwide.

Whether this test can be offered within accredited scope depends on your product and the standard applied; since accreditation is method-based, the scope is confirmed in writing at the quotation stage.

Scope and authorisations

Related Regulations

EU 2017/745 Medical Device Regulation (MDR)
Medical Device Regulation (Türkiye)
ISO 14971 (risk management for medical devices)
ISO 13485 (medical devices — quality management system)

Medikal Cihaz Testleri — What Does This Testing Field Cover?

The section below describes the field that the Haemocompatibility test belongs to; the conditions and acceptance criteria of this particular test are given in the sections above. The scope specific to your product is confirmed in writing at the quotation stage.

Medical device testing shows that a device is safe for the patient and the user and maintains its intended performance. In this family safety is not only about avoiding harm; a device failing to perform its expected function is also treated as a risk. A monitor missing an alarm or a pump delivering the wrong dose is directly a patient safety event.

At the centre of the field is RISK MANAGEMENT, and this is what sets medical apart from other sectors. The risk management process run under ISO 14971 also determines which tests are required. The test list is not copied from a table of standards; it is derived and justified from the device's intended use, the nature and duration of patient contact, the use environment and foreseeable misuse.

Assessment consists of several separate bodies of work, each with its own set of standards. Biocompatibility runs through the ISO 10993 series, electrical device safety through the IEC 60601 series, sterilisation through ISO 11135/11137/17665, packaging through ISO 11607, software through IEC 62304 and usability through IEC 62366. The quality system (ISO 13485) is the framework that binds these together.

Which tests are required is determined by the device's CLASS and its MODE OF CONTACT WITH THE BODY. A product in brief contact with skin and an implant entering the bloodstream do not go through the same test set; the scope is set by a biological evaluation plan prepared under ISO 10993-1. That plan justifies in writing which endpoints are required and why the others are not.

Packaging and sterilisation are taken as seriously as the device itself in this field. For a sterile device the packaging is not a transport container but the barrier that maintains sterility; if the barrier is breached, the device is no longer sterile. Packaging processes are therefore validated and shelf life is supported by real-time ageing data.

For devices containing software, assessment shifts from testing towards PROCESS assurance. IEC 62304 defines which development and verification steps must be followed according to the safety class of the software; the evidence is the traceability of the development process. Testing software does not make it safe — the process record does.

The clinical side is a separate column of the technical file. Test reports show that the device is technically safe; clinical evaluation establishes that the device delivers the intended clinical benefit and that the benefit-risk balance is acceptable. Neither replaces the other.

Method groups in this field

Biocompatibility
Cytotoxicity, irritation, skin sensitisation, systemic toxicity, haemocompatibility, genotoxicity and local effects after implantation. The required endpoints are set by the ISO 10993-1 plan.
Electrical device safety
IEC 60601-1 basic safety and essential performance; EMC, alarm, usability and environmental requirements through the collateral standards.
Sterilisation validation
Validation of sterilisation processes by ethylene oxide, radiation or moist heat; bioburden and sterility assurance level studies.
Packaging
Integrity of the sterile barrier system, seal strength, distribution simulation and shelf-life studies.
Microbiological tests
Bioburden determination, sterility testing, bacterial endotoxin and, where required, carrier validation studies.
Software and usability
IEC 62304 life cycle evidence and use-error focused evaluation under IEC 62366.

Commonly confused in this field

Cytotoxicity alone is not evidence of biocompatibility; the required set of endpoints is determined and justified according to ISO 10993-1.
An ISO 13485 certificate does not confer CE marking; classification under the MDR, the technical file and the notified body process run separately.
Accelerated ageing does not replace real-time ageing; a shelf life claim is supported by real-time data.
A change of material (supplier, pigment, sterilisation method) may require the biological evaluation to be repeated; it is not a silent change.
An assessment made without the collateral and particular standards for IEC 60601-1 is incomplete; which -1-x and -2-x standards were applied must appear in the report.
In vitro diagnostic devices fall under the IVDR rather than the MDR, and laboratory equipment is often on the IEC 61010-1 side.

Which decisions these results support

MDR/IVDR technical file and notified body assessment
Completing the biological evaluation plan
Sterilisation and packaging validation
Determining shelf life and storage conditions
Determining the scope of reassessment after a design change

Related Tests

Frequently Asked Questions About Haemocompatibility — ISO 10993-4

Is the haemolysis test sufficient on its own?

Rarely. Haemolysis covers only one category; for a device in prolonged blood contact, the thrombosis and complement categories must also be assessed.

Are the tests performed with human blood?

The blood source is chosen according to the type of test and the standard's recommendation. The blood source used, its preparation and the anticoagulant are clearly stated in the report.