Genotoxicity Test — ISO 10993-3

What Is Genotoxicity?

The genotoxicity test evaluates the potential of substances released from the device to cause damage to DNA or chromosomes. A battery of several tests is generally applied: gene mutation, chromosomal damage, and in-vivo confirmation if required.

Purpose of Genotoxicity

The purpose is to determine the presence of substances carrying mutagenic, and indirectly carcinogenic, risk in devices with long-term contact or that are implanted.

Which Products Is Genotoxicity Applied To?

Long-term implants
Permanent catheters
Dental implants and filling materials
Absorbable materials
Devices with long-term blood contact

In Which Sectors Is Genotoxicity Used?

Medical DeviceHealthcarePharmaceuticals

Standards Related to Genotoxicity

ISO 10993-3genotoxicity, carcinogenicity and reproductive toxicity test
ISO 10993-1
OECD TG 471
OECD TG 487
OECD TG 476
ISO 11607end product sterile barrier packaging test

Genotoxicity Conditions

Test battery: At least two different in-vitro tests, covering the gene-mutation and chromosomal-damage endpoints
Metabolic activation: Tests are carried out with and without S9 fraction
Extraction: With polar and non-polar solvents, per ISO 10993-12

Equipment for Genotoxicity

Microbiology and cell-culture infrastructure
CO₂ incubator and biosafety cabinet
Microscope and image-analysis system
S9 metabolic-activation system

Sample Requirements for Genotoxicity

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

Duration of Genotoxicity

The test battery typically takes several weeks; the duration extends if in-vivo confirmation is required.

Genotoxicity Procedure

1The need for the test is justified according to the device's contact duration and type.
2The specimen is extracted.
3The bacterial reverse-mutation test (Ames) is applied.
4A micronucleus or chromosome-aberration test is performed on mammalian cells.
5Tests are repeated with and without metabolic activation.
6Positive and negative controls are assessed.
7Results are interpreted together to assess genotoxic potential.

Genotoxicity Acceptance Criteria

The acceptance criterion is that the applied tests show no statistically significant, dose-dependent increase relative to the control groups. Assessment criteria are defined in the relevant OECD and ISO texts.

Evaluation of Results

Results are interpreted as a whole test battery; a borderline finding in one test is evaluated together with the results of the other tests. For a positive finding, chemical characterisation is used to investigate the responsible substance.

Genotoxicity 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

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 Genotoxicity 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 Genotoxicity

Does chemical characterisation substitute for the genotoxicity test?

In some cases, yes. If chemical characterisation performed under ISO 10993-18 and toxicological risk assessment under ISO 10993-17 show that released substances are known and below safe thresholds, testing may not be required. The rationale for this approach is documented in the biological evaluation plan.