Haemocompatibility Test — ISO 10993-4

What Is Hemocompatibility?

The haemocompatibility test evaluates the effect of blood-contacting devices on blood components. Five basic categories are addressed: haemolysis, thrombosis, coagulation, platelets, and haematology and immunology (complement activation). Which categories are tested is determined by the device's type and duration of blood contact.

Purpose of Hemocompatibility

The purpose is to show that the device does not damage blood cells, does not lead to unacceptable clot formation, and does not excessively activate the immune system.

Which Products Is Hemocompatibility Applied To?

Intravenous catheters and cannulas
Dialysis sets and membranes
Heart-lung machine circuit components
Stents and vascular grafts
Blood bags and transfusion sets

In Which Sectors Is Hemocompatibility Used?

Medical DeviceHealthcarePharmaceuticals

Standards Related to Hemocompatibility

ISO 10993-4evaluation of interaction with blood test
ISO 10993-1
ASTM F756
ASTM F1841
ASTM F2382
ISO 11607end product sterile barrier packaging test

Hemocompatibility Conditions

Category selection: Determined according to the device's type of blood contact (indirect, circulating blood, external to circulation) and duration
Blood source: Human or suitable animal blood; anticoagulant and time-of-use are defined
Haemolysis: The haemolysis index is calculated by direct-contact and extract methods

Equipment for Hemocompatibility

Haemolysis test rig and spectrophotometer
Dynamic blood-circulation (loop) system
Haematology analyser
ELISA reader (for complement and platelet markers)
Coagulation analyser

Sample Requirements for Hemocompatibility

The specimen must represent the final, sterilised product
Not raw material — the product that has gone through all manufacturing and sterilisation processes is submitted
The specimen quantity is determined according to the surface-area/extraction ratio prescribed by the standard
The device's type and duration of body contact must be stated
The sterilisation method and, if applicable, residue information must be shared
The blood-contacting surface area must be calculable
For dynamic tests, the specimen must be prepared so it can be connected to the flow circuit

Duration of Hemocompatibility

Several weeks depending on the chosen test package; dynamic thrombogenicity studies require additional time.

Hemocompatibility Procedure

1The device's type and duration of blood contact are determined, and the test categories are selected.
2The specimen is prepared and connected to the circuit if required.
3The haemolysis test is performed by the direct-contact and/or extract method.
4Coagulation and platelet parameters are measured.
5Complement-activation markers are analysed.
6Dynamic thrombogenicity assessment is performed (if required).
7Results are compared with control materials.

Hemocompatibility Acceptance Criteria

The common acceptance criterion for haemolysis is the haemolysis-index classification under ASTM F756 (non-haemolytic, slightly haemolytic, haemolytic). For other categories, acceptance is determined comparatively against reference and control materials.

Evaluation of Results

Results are interpreted separately by category and as a whole. Since individual differences in the blood source affect the result, running controls in parallel and the number of repetitions are important.

Hemocompatibility Report

Applied standard and revision
Specimen description, batch number and sterilisation method
Extraction conditions (solvent, temperature, duration, ratio)
Positive and negative control results
Test results and grading
Assessment and conclusion
Haemocompatibility categories tested and the rationale for selection
Blood source, anticoagulant and time-of-use
Results by category and comparisons with controls

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

MDR (EU) 2017/745
ISO 10993-1 biological evaluation plan

Medikal Cihaz Testleri — What Does This Testing Field Cover?

The section below describes the field that the Hemocompatibility 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 Hemocompatibility

Which haemocompatibility categories are required?

ISO 10993-4 ties category selection to the device's type and duration of blood contact. Haemolysis alone may be sufficient for short-term indirect contact, while long-term contact with circulating blood also requires thrombogenicity, coagulation and complement assessments. The selection is justified in the biological evaluation plan.