Overview
ISO/TR 10993-33:2015 - "Biological evaluation of medical devices - Part 33: Guidance on tests to evaluate genotoxicity - Supplement to ISO 10993-3" is a Technical Report from ISO that provides background and practical guidance to help select and perform genotoxicity tests for medical device biological evaluation. It recognizes differences among regulatory bodies on genotoxicity testing and complements ISO 10993-3 by describing test selection, test performance, data handling and reporting to support biocompatibility assessment.
Key topics and technical content
This TR organizes practical guidance across in vitro and in vivo genotoxicity testing, including:
- Selection of tests and recommended test batteries aligned with device risk and exposure routes.
- Use of in vitro tests: design, limitations and interpretation for assays used to detect genotoxic hazard.
- Use of in vivo tests: when in vivo follow-up is appropriate and how to design animal studies.
- Detailed procedural guidance for common genotoxicity assays, covering:
- Bacterial reverse mutation assay (Ames test): strain preparation, metabolic activation, solvents, exposure concentrations, controls, incubation, data collection and reporting.
- In vitro mammalian chromosome aberration test: cell lines, culture conditions, metabolic activation, chromosome preparation and analysis.
- In vitro micronucleus test: cytokinesis-block use, cell harvest, slide prep, scoring and interpretation.
- Mouse lymphoma (L5178Y) gene mutation assay: culture prep, survival and mutant frequency assessment.
- In vivo erythrocyte micronucleus test: species selection, dosing schedules, sampling and analysis.
- Common technical details: test sample preparation, solvents/vehicles, exposure concentration selection, positive/negative controls, acceptance criteria, statistical treatment of results and test reporting recommendations.
Practical applications
ISO/TR 10993-33:2015 is intended to:
- Guide selection of appropriate genotoxicity assays for medical device extracts and leachables.
- Support laboratory test method setup and quality control for genotoxicity testing.
- Provide context for interpreting positive, negative or equivocal genotoxicity findings.
- Aid regulatory submissions by harmonizing the rationale for test selection and reporting.
Who should use this standard
- Medical device manufacturers and R&D teams preparing biocompatibility dossiers.
- Regulatory affairs professionals assembling safety data for device approval.
- Toxicologists and biocompatibility scientists designing genotoxicity testing strategies.
- Third‑party test laboratories performing genotoxicity assays for medical devices.
Related standards
- ISO 10993-3 (physico-chemical and toxicological methods) - this TR is a supplement to that part of the ISO 10993 series on biological evaluation of medical devices.
Keywords: ISO 10993-33, genotoxicity testing, biological evaluation of medical devices, ISO 10993-3, Ames test, micronucleus test, chromosome aberration, mouse lymphoma assay, biocompatibility testing, medical device regulatory compliance.
Open preview (PDF)Biological evaluation of medical devices — Part 33: Guidance on tests to evaluate genotoxicity — Supplement to ISO 10993-3
