Site of Contact
Confirm where the device directly or indirectly contacts the patient or user, such as intact skin, mucosa, breached surfaces, blood, or tissue.
Biological Safety Evaluation of Medical Devices
Biological safety evaluation of a medical device begins by reviewing the sites and duration of patient or user contact, materials, manufacturing processes, sterilization, chemical characteristics, existing data, and other relevant factors to determine the evaluation needed for the product under application.
Rather than selecting the same test endpoints for every product, it is important to assess whether additional testing is needed based on the biological risks of the specific device and the supporting evidence already available.
Evaluate the Overall Risk of the Device, Not ISO 10993 Alone
The ISO 10993 series is an important foundation for biological safety evaluation.
However, in an actual application, it is not appropriate to mechanically perform every test listed in the standards. The evaluation should combine the intended use, contact conditions, materials, manufacturing processes, chemical information, and existing data for the product under application.
On March 11, 2025, Japan's Ministry of Health, Labour and Welfare fully revised its notification on the basic approach to biological safety evaluation. For an actual application, check the latest notification, Q&A, ISO, JIS, and related guidance.
Information to Confirm Before Starting the Evaluation
Duration of Contact
Confirm cumulative contact time, including repeated use, rather than considering only the duration of a single use.
Materials in Patient-Contacting Parts
Identify the materials that make up patient-contacting parts, including resins, metals, adhesives, colorants, coatings, and additives.
Manufacturing Processes
Confirm how molding, processing, cleaning, bonding, coating, sterilization, packaging, and other processes may change the chemical or physical characteristics of the final product.
Sterilization and Storage Conditions
Review the effects of the sterilization method, sterilization residues, packaging, shelf life, and storage conditions on the materials and final product.
Existing Data
Review raw-material data, chemical characterization, existing biological tests, literature, approved devices, commercial experience, and other available information.
Main Endpoints Considered in Biological Safety Evaluation
Depending on the product characteristics and contact conditions, consider evaluation endpoints such as:
- Cytotoxicity
- Sensitization
- Irritation or intracutaneous reactivity
- Systemic toxicity
- Genotoxicity
- Implantation
- Hemocompatibility
- Carcinogenicity
- Reproductive and developmental toxicity
- Degradation products
- Evaluation of chemicals originating from materials
The same endpoints are not required for every product.
For the product under application, determine which evaluations are needed and which endpoints can be addressed with existing data or scientific justification.
Chemical Characterization and Use of Existing Data
Before adding new animal tests, review material composition, manufacturing processes, extractables and leachables, existing tests, and information from similar products.
When using existing data, do not rely only on the fact that the material name is the same. Review differences in:
- Material composition
- Grade
- Supplier
- Additives
- Manufacturing processes
- Surface treatment
- Sterilization
- Site of contact
- Duration of contact
If it cannot be explained that the differences do not affect biological safety, consider additional chemical analysis or biological testing.
Study Reliability and GLP
For biological safety studies used in a Japanese submission, assess GLP applicability according to the study purpose and content and the regulatory route, and check the reliability of both the report and study records. Under section 2(4) of the MHLW notice of March 11, 2025, studies intended to evaluate biological safety are generally required to follow medical-device GLP; the notice excludes biological safety studies for designated controlled medical devices (指定管理医療機器).
Tests primarily evaluating performance, function, or effectiveness, with safety assessment as a secondary purpose, are not automatically subject to GLP; the applicable requirements for reliable submission data still need to be checked. Determine the purpose and regulatory use of each study rather than treating every ISO 10993 evaluation or nonclinical study in the same way.
From Product Information Review to the Evaluation Report
- 01
Define the Evaluation Scope
Confirm the models under application, accessories, patient-contacting parts, method of use, site of contact, and duration of contact.
- 02
Organize Materials and Manufacturing Processes
Organize information on material composition, additives, adhesives, coatings, cleaning, sterilization, packaging, and related processes.
- 03
Review Existing Information
Review material information, chemical characterization, existing tests, literature, approved devices, and commercial experience.
- 04
Evaluate Biological Risks
Based on the conditions of use and existing information, organize the biological risks that need to be addressed for the product under application.
- 05
Determine Whether Additional Evaluation Is Needed
For items that cannot be adequately addressed by existing data, consider additional analysis or testing.
- 06
Reflect the Evaluation in the Application Dossier
Do not merely list test results. Summarize an integrated conclusion that includes materials, chemical information, conditions of use, and risk management.
Commonly Overlooked Points
- Only the primary material of the patient-contacting part is reviewed, while adhesives or coatings are omitted
- Final-product safety is explained using raw-material safety data alone
- Residues from sterilization or cleaning processes are not assessed
- Contact duration is determined only from a single-use period
- Differences in materials or processes from an existing product are not organized
- The representativeness of the test article for the product under application is not explained
- Test results are not linked to the conclusions of risk management
MK Consulting's Biological Safety Evaluation Support
Organizing the Evaluation Strategy
We review contact conditions, materials, manufacturing processes, sterilization, and existing data to organize the biological risks that should be evaluated.
Reviewing the Usability of Existing Data
We review overseas test data, material data, chemical characterization, approved devices, and related information to determine what can be used in a Japanese application.
Reviewing Test Plans and Application Documents
We organize any additional testing needed and confirm the relationship between the test article, test conditions, acceptance criteria, and the product under application.
For support with biological safety evaluation and approval application documentation, see Approval, Certification & Notification Support.
Frequently Asked Questions
Do All Patient-Contacting Medical Devices Need to Undergo the Same Set of Tests?
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No. Contact site and duration, materials, manufacturing processes, chemical information, and existing data should be reviewed to determine the evaluation needed for each product.
Is Testing in Accordance with ISO 10993 Sufficient?
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Not by itself. A comprehensive evaluation is needed that includes material information, manufacturing processes, clinical conditions of use, chemical characteristics, existing data, and test results.
Can Tests Performed Overseas Be Used in a Japanese Application?
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In some cases, yes. Confirm the version of the test standard, the identity or equivalence of the test article to the product submitted in Japan, test conditions, and differences from Japanese requirements. Also assess GLP applicability based on the study purpose, content, and submission route, and verify the reliability of the report and study records.
Is Retesting Required After a Material or Manufacturing-Process Change?
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Assess the impact of the change on biological safety and consider additional testing when the impact cannot be adequately explained using existing data.
Contact Us About Biological Safety Evaluation
We review material information, manufacturing processes, overseas test data, and existing evidence to organize any additional evaluation needed for a Japanese application.
Contact us about biological safety evaluation