Biological evaluation of medical devices - Part 1: Requirements and general principles for the evaluation of biological safety within a risk management process
1Key Takeaways
This standard provides guidelines for the evaluation of biological safety within the risk management process for medical devices. It outlines the general principles and requirements necessary to ensure the safety of medical devices in terms of their biological compatibility. The document covers the fundamental aspects …
2Expert Interpretation
ISO 10993-1:2025 is the core standard for biological evaluation of medical devices, specifying the requirements and general principles for evaluating biological safety during risk management. It applies to medical devices that come into direct or indirect contact with the human body, covering the assessment of biological effects such as cytotoxicity, sensitization, and irritation, and guiding manufacturers in conducting biological risk analysis, evaluation, and control.
Standard Overview
ISO 10993-1:2025, "Biological evaluation of medical devices – Part 1: Evaluation requirements and general principles in a risk management process," is a fundamental international standard in the field of biological evaluation of medical devices. This standard provides medical device manufacturers with a systematic framework for biological evaluation, integrating biological safety evaluation into the ISO 14971 risk management process. The standard applies to medical devices that come into direct or indirect contact with patients or users (such as medical masks), covering the entire lifecycle from design and development to eventual discontinuation.
Major Updates
Compared to the 5th edition in 2018, the 6th edition has undergone a complete reorganization. Major changes include: aligning the title with the ISO 14971 risk management framework; adding guidance on calculating exposure duration; clarifying the requirements for device characteristic identification and biohazard identification; revising the list of biological effects (formerly called biological endpoints); replacing "external communication" with expressions reflecting specific tissue exposure; changing "post-implantation effects" to "local effects after tissue exposure"; revising Annex A and adding Annex B to explain the reasons for changes in biological effects.
Biological Evaluation Framework
Biological evaluation (biocompatibility evaluation) must be conducted in accordance with the risk management process of ISO 14971, including identifying biohazards, assessing relevant biological risks, and determining their acceptability. The evaluation is planned, implemented, and reported by qualified personnel. The standard emphasizes animal welfare, requiring the reduction, optimization, and substitution of animal testing as much as possible.
The standard divides biological evaluation into four steps: biological evaluation planning, biological risk analysis, biological risk assessment, and biological risk control. Risk analysis includes device description and classification, biohazard identification, and determination of relevant biological effects; risk estimation is based on existing data or supplementary testing; risk assessment determines whether the risk is acceptable; and risk control involves prioritizing measures (intrinsic safety design, protective measures, and safety information).
Comparison Table of Biological Effects
| Type of Exposure | Limited Exposure (≤24h) | Short-Term Exposure (>24h~30d) | Long-Term Exposure (>30d) |
|---|---|---|---|
| Intact Skin | Cytotoxicity, Sensitization, Irritation | Cytotoxicity, Sensitization, Irritation | Cytotoxicity, Sensitization, Irritation |
| Intact Mucosa | Cytotoxicity, Sensitization, Irritation | Cytotoxicity, Sensitization, Irritation, Systemic Toxicity, Local Effects After Tissue Contact, Genotoxicity | Cytotoxicity, sensitization, irritation, systemic toxicity, local effects after tissue contact, genotoxicity, carcinogenicity.Cytotoxicity, sensitization, irritation, systemic toxicity, local effects after tissue contact, genotoxicity, carcinogenicity, blood compatibility |
Key Terminology Explanation
Biocompatibility: The ability of a medical device to perform its intended function and produce an appropriate host response in a specific application.
Biological effects: Observable or measurable responses of cells or organisms to the physical properties or chemical components of a medical device.
Biological equivalence: When the device being evaluated is sufficiently similar to a comparable device with existing safety data in chemical, physical properties and manufacturing processes, and no new or increased risks are found, biological equivalence is established.
Leachable matter: Substances released by a medical device during clinical use.
Total exposure period: The number of days of exposure from the first to the last use of the medical device.
Implementation Recommendations
- Establish a biological evaluation plan: Clearly define the device description, intended use, reasonably foreseeable misuse, exposure classification (type and duration), biological effects list, data gap analysis, and testing strategy.
- Emphasis on chemical characterization: Conduct material chemical characterization according to ISO 10993-18 to identify potentially hazardous components as the basis for risk analysis.
- Make reasonable use of existing data: Prioritize assessing biological risks using existing data such as literature, supplier information, and clinical experience, avoiding unnecessary animal testing.
- Dynamically manage risks: Continuously collect user feedback and adverse event information in the post-production stage, and update the biological evaluation in a timely manner when the design, process, or intended use changes.
- Pay attention to special factors: For devices that may absorb, degrade, or release particulate matter or contain known hazardous components, additional assessments of toxicokinetics, immunotoxicity, and neurotoxicity are required.
- Ethics and Animal Welfare: When animal testing is necessary, strictly follow ISO 10993-2 and implement the 3R principle (replace, reduce, optimize).
Standard Framework Comparison Table
| Dimensions | ISO 10993-1:2018 | ISO 10993-1:2025 |
|---|---|---|
| Title | Biological Evaluation in Risk Management Processes | Biological Evaluation in Risk Management Processes (Closer Alignment with ISO 14971) |
| Contact Categories | Surface Contact, External Communication, Implantation | Intact Skin, Intact Mucosa, Damaged Surface/Internal Tissue (Non-Blood), Circulating Blood |
| Biological Effects | Listed in Table A.1, including sub-items such as acute toxicity. Systemic toxicity is standardized and explained in the footnotes as being assessed according to the duration of use. Genotoxicity requirements: Only devices with prolonged contact with mucous membranes or blood are required. All short-term contact (except for intact skin) requires genotoxicity assessment. Carcinogenicity requirements: Only devices with prolonged contact with internal tissues or blood are required. Devices with prolonged contact with mucous membranes also require carcinogenicity assessment. Material thermal effects: Listed in Table A.1. Moved to 6.5.10.5 "Other biological effects" for discussion. Appendix AContains extensive material selection guidelines | Simplified, primarily providing material characterization guidance |
| Added Appendix B | None | Theoretical basis for explaining changes in biological effects |
Application Cases
Case Study: Absorbable Bone Fixation Devices
These devices involve long-term contact with internal tissues (non-blood), requiring assessment of cytotoxicity, sensitization, irritation, systemic toxicity (acute and chronic), local effects after tissue contact, genotoxicity, and carcinogenicity. Furthermore, due to the degradability of the material, degradation testing (ISO 10993-13/14/15), toxicokinetic studies (if applicable), and assessment of the local and systemic effects of degradation products and particulate matter are also required. Manufacturers should confirm the list of degradation products through chemical characterization and determine safety thresholds in conjunction with toxicological risk assessments. In summary, ISO 10993-1:2025 provides a clearer, more systematic, and scientific approach to the biological evaluation of medical devices, emphasizing a risk-based management philosophy and encouraging the use of alternative methods to reduce animal testing. Manufacturers should carefully study the changes in the new version to ensure that biological evaluations meet the latest requirements.