Overview
ISO 10993-23:2021/Amd 1:2025 is an important amendment to the international standard for the biological evaluation of medical devices, specifically focusing on Part 23: Tests for irritation. This amendment introduces additional in vitro reconstructed human epidermis (RhE) models for assessing skin irritation potential caused by medical devices. Developed by ISO Technical Committee ISO/TC 194 in collaboration with CEN/TC 206, it reflects the latest advancements in alternative testing methods that reduce reliance on animal testing.
This update is critical for manufacturers, regulators, and researchers involved in the safety assessment of medical devices, offering validated and scientifically qualified methods that utilize reconstructed human skin models. It emphasizes a stepwise approach starting with in vitro irritation testing prior to in vivo animal or human tests, ensuring a more ethical and sensitive assessment process.
Key Topics
- In vitro irritation testing using RhE models adapted for medical device extracts
- Validation and inclusion of two new RhE models: KeraSkin™ and LabCyte EPI-MODEL24 under OECD Test Guideline 439
- Comparison and equivalence of new models to established RhE models like EpiDerm™ and SkinEthic™
- Protocols to detect interference in test results, such as direct reduction of MTT reagent or chemical tissue coloring
- Specific test procedures, including sample application volumes, incubation times, and photometric measurement wave lengths (e.g., 570 nm, 650 nm)
- Classification criteria for irritant activity based on tissue viability thresholds (≤ 50%) across polar and non-polar solvent extracts
- Detailed plate layout configurations for standardized readings on 96-well microtitre plates
- Emphasis on the preference for in vitro tests to replace animal tests where feasible, aligned with ISO 10993-2 guidelines
Applications
This amendment directly supports the development and regulatory submission of medical devices by providing:
- Validated skin irritation testing methods for extracts from materials such as polyvinylchloride (PVC) and silicone widely used in device manufacture
- Procedures to efficiently screen device components for potential skin irritants using human-relevant 3D reconstructed epidermis models
- A scientifically robust approach to comply with international biocompatibility regulations and reduce animal testing in accordance with global regulatory policies
- Enhanced confidence in safety evaluation studies by adopting internationally recognized OECD-validated protocols ensuring reproducibility and reliability
- Support for manufacturers to implement integrated testing strategies combining in vitro data with clinical evaluations when required
- Reference testing standards facilitating communication with regulatory bodies like the FDA and EMA for medical device approval processes
Related Standards
ISO 10993-23:2021/Amd 1:2025 is part of the comprehensive ISO 10993 series dedicated to the biological evaluation of medical devices. Additional relevant standards include:
- ISO 10993-2:2023 – Animal welfare requirements and testing strategies for biological evaluation
- ISO 10993-1 – Evaluation and testing within a risk management process
- OECD Test Guideline 439 – In vitro skin irritation testing using reconstructed human epidermis
- ISO 10993-12 – Sample preparation and reference materials for biological testing
- ISO 10993-10 – Irritation and skin sensitization tests
Together, these standards form an integrated framework facilitating consistent, ethical, and scientifically rigorous biocompatibility assessment for medical devices globally.
By adopting ISO 10993-23:2021/Amd 1:2025, stakeholders align with cutting-edge in vitro methodologies, support animal welfare initiatives, and ensure reliable skin irritation evaluation for safer medical device innovation. For more details and implementation guidance, visit the official ISO website at www.iso.org.
Open preview (PDF)Biological evaluation of medical devices — Part 23: Tests for irritation — Amendment 1: Additional in vitro reconstructed human epidermis models