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Biocompatibility and Sterilisation

Biocompatibility — ISO 10993 series​

Japan has adopted the ISO 10993 series as recognised standards for biocompatibility evaluation. The framework follows the ISO 10993-1:2018 approach — a risk-based evaluation that considers:

  • Nature and duration of patient contact (surface contact, blood contact, tissue contact; limited / prolonged / permanent)
  • The biological endpoints relevant to the contact category
  • Whether the materials have a history of safe clinical use that can be used as supporting evidence

ISO 10993 standards recognised in Japan:

  • ISO 10993-1: Evaluation and testing within a risk management process
  • ISO 10993-2: Animal welfare requirements
  • ISO 10993-3: Tests for genotoxicity, carcinogenicity, and reproductive toxicity
  • ISO 10993-4: Selection of tests for interactions with blood
  • ISO 10993-5: Tests for in vitro cytotoxicity
  • ISO 10993-10: Tests for skin sensitisation
  • ISO 10993-12: Sample preparation and reference materials
  • And others

PMDA follows the ISO 10993-1:2018 framework for determining which tests are required for a specific device, though some PMDA guidance documents may reference earlier versions or include additional device-specific endpoints beyond the standard ISO approach. A biocompatibility evaluation rationale — explaining which endpoints were assessed, which tests were conducted, and the basis for concluding biocompatibility — must be included in the application dossier.

Sterilisation validation​

For sterile devices, sterilisation validation data is required in the application. Japan recognises the key ISO sterilisation standards:

  • ISO 11135 (EO sterilisation)
  • ISO 11137 series (radiation sterilisation)
  • ISO 17665-1 (steam sterilisation)
  • ISO 13485 requirements for sterilisation process controls

PMDA expects the validation to cover: sterility assurance level (SAL ≤10⁻⁶), method selection rationale, bioburden data, and ongoing monitoring requirements.

PMDA-specific expectations​

PMDA applies the ISO 10993-1:2018 framework but may have device-type-specific expectations articulated in PMDA guidance documents. For novel materials or complex contact scenarios, early PMDA consultation on the biocompatibility testing plan is advisable.

PMDA Biocompatibility Guidance Documents

PMDA has issued device-specific biocompatibility expectations in several guidance documents (available in Japanese from the PMDA website) for categories including cardiovascular devices, ophthalmologic implants, and wound care products. These documents may specify additional endpoints beyond ISO 10993-1 risk-based selection or recommend specific test methods. Review PMDA's published guidance for your device category before finalising your biocompatibility testing plan.