Genotoksisite – ISO 10993-3

What Is Genotoxicity — ISO 10993-3?

The genotoxicity assessment examines whether substances released from the device damage genetic material. ISO 10993-3 requires a battery of at least two complementary in vitro tests: a bacterial gene mutation test (Ames) and a test showing chromosomal damage in mammalian cells.

Purpose of Genotoxicity — ISO 10993-3

The purpose is to determine the material's potential to be mutagenic or cause chromosomal damage. This endpoint is the first indicator of carcinogenicity risk, particularly for long-term contact and implanted devices.

Which Products Is Genotoxicity — ISO 10993-3 Applied To?

Long-term implants
Absorbable materials
Long-term blood-contacting devices
Devices with a new material or new additive
Dental fillings and adhesives

In Which Sectors Is Genotoxicity — ISO 10993-3 Used?

Medical DevicePharmaceuticalsHealthcareBiotechnology

Standards Related to Genotoxicity — ISO 10993-3

ISO 10993-3genotoxicity, carcinogenicity and reproductive toxicity test

Genotoxicity — ISO 10993-3 Conditions

Test battery: At least two complementary in vitro tests
Metabolic activation: Tests are run with and without S9 mix
Extraction: Polar and non-polar extracts per ISO 10993-12
Controls: Positive and vehicle controls in every test

Equipment for Genotoxicity — ISO 10993-3

Microbiology and cell culture laboratory
Incubators and biosafety cabinets
Microscope and automated colony/micronucleus counting systems
S9 fraction preparation and storage setup
Extraction oven

Sample Requirements for Genotoxicity — ISO 10993-3

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 Genotoxicity — ISO 10993-3

The two-test battery, together with culture preparation and repeats, is several weeks of work.

Genotoxicity — ISO 10993-3 Procedure

1The device's category and requirement are determined per ISO 10993-1.
2Extracts are prepared per ISO 10993-12.
3The bacterial reverse mutation test is set up (with and without S9).
4The chromosomal damage test in mammalian cells is set up.
5Positive and negative controls are run alongside.
6Colony or micronucleus counts are performed.
7Results are assessed statistically and the battery is interpreted as a whole.

Genotoxicity — ISO 10993-3 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 result of the battery as a whole, not a single test. On a positive finding, the responsible component must be identified and, if needed, confirmed with further tests; the finding does not directly mean the device is rejected — it feeds into the risk assessment.

Genotoxicity — ISO 10993-3 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 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 — ISO 10993-3

Why are two different tests required?

Genetic damage arises through different mechanisms: point mutations and chromosome breaks are captured by different tests. A single test does not cover all mechanisms.

Why is S9 mix added?

Some substances become genotoxic only after being metabolised in the body, not on their own. The S9 liver enzyme fraction mimics this metabolism in the in vitro setting.