On May 1, 2025, the amendment ISO 10993-23:2021/Amd 1:2025 was published, titled:
“Biological evaluation of medical devices — Part 23: Tests for irritation — Amendment 1: Additional in vitro reconstructed human epidermis models.”
This amendment brings significant updates to the ISO 10993-23:2021 standard, introducing additional in vitro reconstructed human epidermis (RhE) models for skin irritation testing. These updates reflect scientific and technological advances in the biological evaluation of medical devices.
In addition to the EpiDerm™ and SkinEthic™ RHE models already recognized in the 2021 version of the standard, Amendment 1:2025 includes additional RhE models listed in OECD Test Guideline 439. These models were adopted for medical device evaluation after demonstrating predictive capacity equivalent to the previously accepted models in validation studies.
The newly introduced models are the LabCyte EPI-MODEL24 and KeraSkin™ RhE model, which are 3D reconstructed human epidermis models composed of human epidermal keratinocytes.
Here are the main updates compared to the original version:
Expansion of in vitro methods with RhE models
- While the 2021 version already allowed for the use of in vitro methods, Amendment 1 expands the list of validated RhE models.
- Additional commercial models are now recognized, having been tested for reproducibility and sensitivity.
- This strengthens the use of in vitro methods as a standard alternative to animal testing, particularly to intracutaneous tests in rabbits.
More detailed acceptance criteria
- The amendment clarifies the acceptance criteria for in vitro tests, providing more precise definitions of the thresholds within which a material is considered irritant or non-irritant.
- This contributes to standardizing result interpretation and reducing inter-laboratory variability.
Guidance for extracted materials (e.g., polymers)
- New guidelines are introduced for the preparation and extraction of materials (such as silicone or PVC) to be tested with RhE models.
- The amendment outlines the compatibility of certain materials and supports the validation of methods for solid materials, not just liquids or semi-liquids.
Contribution to the 3Rs approach (Replacement, Reduction, Refinement)
- The document reinforces the shift from in vivo tests to ethically and scientifically validated in vitro approaches, in line with European and international policies aimed at reducing animal use in testing.
Practical impact
- Medical device manufacturers must now revise their testing protocols to include the newly approved RhE options.
- Laboratories will need to verify the validity and accreditation of the new models they intend to use.
ISO Amendment Link: https://www.iso.org/obp/ui/en/#iso:std:iso:10993:-23:ed-1:v1:amd:1:v1:en
