Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
This guidance document outlines the FDA's current thinking on the use of ISO 10993-1 for biological evaluation of medical devices that come into direct or indirect contact with the human body. It covers: - Use of risk assessment for biocompatibility evaluations - Use of ISO 10993-1 and FDA-modified matrix to determine relevant biocompatibility endpoints - General biocompatibility testing considerations including test article preparation - Specific considerations for various biocompatibility tests - Chemical assessment recommendations - Labeling devices as -free
Recommended Actions
- Conduct risk assessment to determine biocompatibility evaluation needs
- Document device categorization based on nature and duration of body contact
- Review available information (literature, previous testing, clinical experience) before conducting new testing
- If testing needed:
- Use final, sterilized device when possible
- Follow appropriate test methods and standards
- Consider specialized testing for novel materials
- Document test article comparability to final device
- Provide chemical assessment information when required for:
- Novel materials
- New chemicals in formulation
- Known toxic materials
- Degradable materials
- Unexpected findings
- Maintain appropriate documentation in Device Master Record
- Include appropriate information in regulatory submissions:
- Risk assessment summary
- Test reports or rationales
- Chemical characterization data if needed
- Appropriate labeling
- Consider Q-Submission process to obtain FDA feedback on planned approach
- Monitor post-market experience to identify potential biocompatibility issues
- Update risk assessment if changes made to device materials, manufacturing, or processing
Key Considerations
Non-clinical testing
- Testing should be conducted on final, sterilized devices whenever possible
- If final device cannot be used, test article should undergo same manufacturing and sterilization processes
- For in situ polymerizing/absorbable materials, testing needed at various timepoints during polymerization/degradation
- Consider mechanical failure impacts on biological response
- For submicron/nanotechnology components, specialized testing techniques may be needed
Labelling
- Avoid using terms like “latex-free”, “DEHP-free” etc. as they may give false sense of security
- Use statements like “Not made with natural rubber latex” instead
- If making “-free” claims, provide data showing device does not contain material at levels that could cause adverse events
Biocompatibility
- Consider chemical characteristics and nature/duration of body contact
- Evaluate cytotoxicity, sensitization, irritation, systemic toxicity, implantation etc. based on device category
- Chemical characterization may be needed for novel materials
- Consider degradation assessment for absorbable devices
- Address material-mediated pyrogenicity for relevant devices
- Consider reproductive/developmental toxicity for certain devices
Safety
- Evaluate both local and systemic risks
- Consider physical characteristics that could cause unwanted tissue response
- Assess carcinogenicity potential for long-term contact devices
- Consider impact of processing/sterilization on safety
Other considerations
- Use risk management process framework
- Consider available information before conducting new testing
- Document comparisons to previously marketed devices
- Maintain appropriate quality system controls
- Consider combination product specific requirements if applicable
Relevant Guidances
- Chemical Analysis in Medical Device Biocompatibility Assessment (Draft)
- Immunological Testing for Medical Devices: Evaluation and Assessment of Adverse Effects
- Biological Evaluation of Medical Devices Standards in the Accreditation Scheme for Conformity Assessment (ASCA) Pilot Program
- Biocompatibility Testing Standards and Accreditation Requirements in the ASCA Program (Draft)
Related references and norms
- ISO 10993-1: Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process
- ISO 10993-3: Tests for genotoxicity, carcinogenicity and reproductive toxicity
- ISO 10993-5: Tests for in vitro cytotoxicity
- ISO 10993-6: Tests for local effects after implantation
- ISO 10993-10: Tests for irritation and skin sensitization
- ISO 10993-12: Sample preparation and reference materials
- ISO 10993-18: Chemical characterization of medical device materials
- ASTM F756: Assessment of Hemolytic Properties of Materials
- ASTM F619: Extraction of Materials Used in Medical Devices
- OECD 471: Bacterial Reverse Mutation Test
- OECD 473: In Vitro Mammalian Chromosome Aberration Test
- OECD 474: Mammalian Erythrocyte Micronucleus Test
Original guidance
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- HTML / PDF
- Issue date: 2023-09-08
- Last changed date: 2024-09-05
- Status: FINAL
- Official FDA topics: Medical Devices, Errors, and Problems, Premarket Approval (PMA), 510(k), Premarket, Biologics, HUD/HDE, Investigational Device Exemption (IDE), Safety - Issues
- ReguVirta summary file ID: edf696660325805ba7f17acd5a464ec4
This post is licensed under CC BY 4.0 by the author.