Biocompatibility Evaluation Requirements

1. I. Scope and Principles

• Biological safety evaluation is mandatory for any device with direct or indirect patient contact.
• Biological safety evaluation needs to follow ISO 10993-1 Biological evaluation of medical devices – Part 1 or JIS T 0993-1.

 

II. Approach to Biological Safety Evaluation

• Biological safety evaluation needs to be conducted on the finished product, considering raw materials, body contact area and duration.
• If biological safety assessment results indicate a biological risk, the medical device should not be immediately deemed non-compliant. Instead, a comprehensive risk assessment incorporating the biological safety assessment results should be conducted in accordance with ISO 14971 and/or JIS T 14971, and appropriate risk controls should be implemented.
• Animal welfare must be respected in accordance with the 3Rs principles, Replacement, Reduction, and Refinement.
• Biological safety tests must be conducted in compliance with Good Laboratory Practice (GLP). However, GLP does not apply to designated controlled devices(指定管理医療機器).

 

III. Summary for the documentation (STED)

1. Conduct risk assessment (collect information on raw materials, clinical use, equivalency, physicochemical properties)
2. Confirm device category and relevant endpoints
3. Determine the need for additional tests and conduct as necessary
4. Provide overall biological risk assessment

 

IV. Relevant Standards

ISO 10993 series:

• ISO 10993-3 (genotoxicity/carcinogenicity/reproductive toxicity)
• ISO 10993-4 (hemocompatibility)
• ISO 10993-5 (cytotoxicity)
• ISO 10993-6 (implantation)
• ISO 10993-10 (sensitization)
• ISO 10993-11 (systemic toxicity)
• ISO 10993-23 (irritation)
• ISO/TS 10993-20 (immunotoxicity)

 

V. Other Major relevant standards

• ISO 10993-1 (General principles)
• ISO 10993-2 (Animal welfare)
• ISO 10993-7 (Ethylene oxide residuals)
• ISO 10993-12 (Sample preparation and reference materials)
• ISO 10993-17 (Toxicological risk assessment)
• ISO 10993-18 (Chemical characterization)

 

VI. Other major reference standards

• ISO/TS 21726: Biological evaluation of medical devices – Application of the threshold of toxicological concern (TTC) for assessing biocompatibility of medical device constituents
• ISO 18562 series: Biocompatibility evaluation of breathing gas pathways in healthcare applications
• ISO 14971: Medical Devices – Application of risk management to medical devices
• ISO 9394: Ophthalmic optics – Contact lenses and contact lens care products – Determination of biocompatibility by ocular study with rabbit eyes

 

Contact our team today to learn how we can support your entry into the Japan market and ensure compliance with PMDA requirements.

 

References

Revisions to Biological Safety Evaluation (「医療機器の製造販売承認申請等に必要な生物学的安全性評価の基本的考え方についての改正について」の全部改正について, 医薬機審発0311第1号(令和7年3月11日))