USA Regulatory ServicesBiological evaluation is a systematic, risk-based process used to determine the potential for an unacceptable adverse biological response resulting from direct or indirect contact between a medical device and the human body. It assesses the biological safety of the device's component materials in relation to its intended use, nature of body contact, and duration of contact.
Refer Guidance Document for further Information - Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process".
ISO 10993 Series: Standards for Biological Evaluation
The ISO 10993 series provides a framework for evaluating the biological safety of medical devices through risk assessment, chemical characterization, and the assessment of relevant biological effects. Each part addresses a specific aspect of the evaluation, supporting the selection of appropriate methods and endpoints based on the device's characteristics.
| Standard | Title / Scope |
|---|---|
| ISO 10993-1 | Biological evaluation of medical devices - Part 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 10993-6 | Tests for local effects after implantation |
| ISO 10993-7 | Ethylene oxide sterilization residues |
| ISO 10993-9 | Framework for identification and quantification of degradation products |
| ISO 10993-10 | Tests for skin sensitization |
| ISO 10993-11 | Tests for systemic toxicity |
| ISO 10993-12 | Sample preparation and reference materials |
| ISO 10993-13 | Degradation products from polymeric medical devices |
| ISO 10993-14 | Degradation products from ceramics |
| ISO 10993-15 | Degradation products from metals and alloys |
| ISO 10993-16 | Toxicokinetic study design for degradation products and leachables |
| ISO 10993-17 | Toxicological risk assessment of medical device constituents (2023 edition) |
| ISO 10993-18 | Chemical characterization of medical device materials within a risk management process |
| ISO 10993-19 | Physico-chemical, morphological and topographical characterization of materials |
| ISO 10993-20 | Principles and methods for immunotoxicology testing of medical devices |
| ISO 10993-22 | Guidance on nanomaterials |
| ISO 10993-23 | Tests for irritation |
| ISO 10993-33 | Guidance on tests to evaluate genotoxicity – Supplement to ISO 10993-3 |
Key Areas of Biological Evaluation
The ISO 10993 series provides guidance for assessing these endpoints and determining whether additional testing or supporting evidence is required.
Key areas include:
1. Biological Risk Assessment: Identification and evaluation of potential adverse biological responses associated with device materials and their intended use.
2. Biological Endpoint Selection: Determination of relevant biological effects based on the device's contact category and duration of exposure.
3. Chemical Characterization: Assessment of device material composition and potential chemical constituents, including substances that may be released from the device.
4. Biocompatibility Testing: Evaluation of relevant endpoints, such as cytotoxicity, sensitization, irritation, systemic toxicity, hemocompatibility, implantation effects, and other applicable biological effects.
5. Degradation Assessment: Evaluation of degradation products and their potential biological implications, where relevant.
6. Documentation and Reporting: Preparation and review of biological evaluation documentation and supporting evidence.
Risk-Based Selection of Biocompatibility Tests
Not every medical device requires every test within the ISO 10993 series. The appropriate evaluation strategy is determined by considering the device's intended use, nature and duration of body contact, material composition, manufacturing and sterilization processes, existing scientific evidence, and identified biological risks.
Existing data, chemical characterization, and scientifically justified assessments may provide sufficient evidence for certain endpoints. Where additional testing is necessary, the selection and extent of testing should be justified based on the device's specific characteristics and applicable regulatory recommendations.
For modified devices, the evaluation should also determine whether the modification could affect the biological safety of components that directly or indirectly contact the human body.
Biological Evaluation Documentation and Regulatory Support
The findings of the biological evaluation should be documented within the device's risk management process. Depending on the device and applicable regulatory requirements, the documentation may include:
- Biological Evaluation Plan (BEP)
- Scientific Justifications
- Biological Evaluation Report (BER)
- Waiver Report
The 3R principles promote the ethical use of animals in scientific research and the evaluation of the safety of biological devices.
-Replace: If possible, alternative methods such as in vitro testing and computational models are used instead of animal testing.
-Reduce: reduce the number of animals used without compromising scientific validity.
-Refine: Modify procedures to minimise the pain, suffering and distress of animals. 3R supports ethical and risk-based biological evaluation in accordance with ISO 10993-1, promotes alternative testing to animals and ensures patient safety.
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