Overview
ISO 10993-3:2014 - Biological evaluation of medical devices - Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity - provides strategies and test-selection guidance for assessing the potential of medical devices and their materials to cause genotoxicity, carcinogenicity, or reproductive/developmental toxicity. Applicable when a risk assessment indicates these hazards are relevant, the standard helps manufacturers, toxicologists and test laboratories decide what tests are necessary and how to interpret results within a device-specific risk management process.
Key technical topics and requirements
- Risk-based test strategy: Testing is required only when justified by a device-specific risk assessment that considers chemical constituents, manufacturing residues, degradation products, exposure routes and clinical use.
- Genotoxicity testing: Guidance on in vitro and in vivo genotoxicity assays, sample preparation and follow-up evaluation to maximize test sensitivity.
- Carcinogenicity testing: Evaluation strategies for long-term studies, including considerations for implantation studies and criteria for study design.
- Reproductive and developmental toxicity: Selection of appropriate reproductive toxicity tests (screening and full studies) and sample-preparation requirements.
- Sample preparation: Procedures for extracts, leachables and resuspended device-related materials consistent with ISO 10993-12 to ensure relevant exposure in test systems.
- Reporting and follow-up: Requirements for test reports and structured follow-up evaluation (flowchart guidance) when initial results indicate concern.
- Normative and informative annexes: Practical guidance (Annex A–F) on sample prep, follow-up flowcharts, rationale for test systems, implantation study considerations and in vitro embryo toxicity tests.
- Referenced test methods: Cross-references to OECD and other standard methods (e.g., OECD 471, 473, 476, 487, OECD 414/415/416/421/451/453) for validated assay protocols.
Practical applications - who uses ISO 10993-3:2014
- Medical device manufacturers performing biocompatibility and safety assessments.
- Regulatory affairs professionals preparing premarket submissions.
- GLP-certified testing laboratories designing genotoxicity, carcinogenicity or reproductive toxicity studies.
- Toxicologists and clinical safety assessors conducting device-specific risk estimation.
- Notified bodies and regulatory agencies evaluating evidence for device approval.
Related standards
- ISO 10993-1: Evaluation and testing within a risk management process
- ISO 10993-12: Sample preparation and reference materials
- ISO 10993-6, -5, -11, -18 and other parts of the ISO 10993 series for complementary biocompatibility, chemical characterization and toxicity guidance
This standard is essential when assessing irreversible biological hazards from medical devices and integrates with ISO 10993 risk management, OECD test methods and laboratory best practices for reliable genotoxicity, carcinogenicity and reproductive toxicity evaluation.
Open preview (PDF)Biological evaluation of medical devices — Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity
