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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

  1. Conduct risk assessment to determine biocompatibility evaluation needs
  2. Document device categorization based on nature and duration of body contact
  3. Review available information (literature, previous testing, clinical experience) before conducting new testing
  4. 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
  5. Provide chemical assessment information when required for:
    • Novel materials
    • New chemicals in formulation
    • Known toxic materials
    • Degradable materials
    • Unexpected findings
  6. Maintain appropriate documentation in Device Master Record
  7. Include appropriate information in regulatory submissions:
    • Risk assessment summary
    • Test reports or rationales
    • Chemical characterization data if needed
    • Appropriate labeling
  8. Consider Q-Submission process to obtain FDA feedback on planned approach
  9. Monitor post-market experience to identify potential biocompatibility issues
  10. 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

  • 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
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