ISO 10993-23:2021/Amd 1:2025
(Amendment)Biological evaluation of medical devices — Part 23: Tests for irritation — Amendment 1: Additional in vitro reconstructed human epidermis models
Biological evaluation of medical devices — Part 23: Tests for irritation — Amendment 1: Additional in vitro reconstructed human epidermis models
Évaluation biologique des dispositifs médicaux — Partie 23: Essais d'irritation — Amendement 1: Modèles supplémentaires d'épiderme humain reconstruit in vitro
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Standards Content (Sample)
International
Standard
ISO 10993-23
First edition
Biological evaluation of medical
2021-01
devices —
AMENDMENT 1
Part 23:
2025-05
Tests for irritation
AMENDMENT 1: Additional in vitro
reconstructed human epidermis models
Évaluation biologique des dispositifs médicaux —
Partie 23: Essais d'irritation
AMENDEMENT 1: Modèles supplémentaires d'épiderme humain
reconstruit in vitro
Reference number
ISO 10993-23:2021/Amd.1:2025(en) © ISO 2025
ISO 10993-23:2021/Amd.1:2025(en)
© ISO 2025
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ii
ISO 10993-23:2021/Amd.1:2025(en)
Foreword
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This document was prepared by Technical Committee ISO/TC 194, Biological and clinical evaluation of medical
devices, in collaboration with the European Committee for Standardization (CEN) Technical Committee CEN/
TC 206, Biological and clinical evaluation of medical devices, in accordance with the Agreement on technical
cooperation between ISO and CEN (Vienna Agreement).
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iii
ISO 10993-23:2021/Amd.1:2025(en)
Biological evaluation of medical devices —
Part 23:
Tests for irritation
AMENDMENT 1: Additional in vitro reconstructed human
epidermis models
Introduction, fifth paragraph
Replace the paragraph with the following paragraphs:
Traditionally, tests in small animals have been performed prior to testing on humans to help predict
human responses. More recently, in vitro tests as well as human tests have been added as adjuncts
or alternatives. For skin irritation testing of neat chemicals, in vitro tests were developed using
[31]
reconstructed human epidermis (RhE) models . The method was adapted for detection of irritant
chemicals in medical device extracts. The results of a large interlaboratory study that tested two types
of RhE models showed that these models can also be used to detect the presence of irritant chemicals
extracted from polymeric materials [polyvinylchloride (PVC) and silicone] commonly used in the
[6]
manufacture of medical devices . This method was found to be equally sensitive in the detection of
low concentrations of some strong irritant compounds when compared to the human patch testing and
[14]
intracutaneous rabbit test . Therefore, a stepwise approach for irritant testing can start with the in
vitro RhE model.
In 2023, two new type RhE models listed in OECD 439 were adopted for medical devices after they
demonstrated equivalent predictive capacity compared to the two other RhE models in interlaboratory
[42][43][44]
studies .
Clause 4, second paragraph
Replace the paragraph with the following paragraphs:
Preference for in vitro tests instead of in vivo tests in accordance with ISO 10993-2, shall be considered,
with replacement of the latter as new in vitro tests are scientifically validated and qualified for use with
medical devices and become reasonably and practicably available. The results of a large interlaboratory
study that tested two types of RhE models showed that these models can also be used to detect the
presence of irritant chemicals extracted from polymeric materials [polyvinylchloride (PVC) and
[6]
silicone] commonly used in the manufacture of medical devices . This method was found equally
sensitive to detect low concentrations of some strong irritant compounds when compared to the human
[14]
patch testing and intracutaneous rabbit test . Therefore, the in vitro irritation test shall be performed
before animal testing or human patch test is considered.
In 2023, two new type RhE models listed in OECD 439 were adopted for medical devices after they
demonstrated equivalent predictive capacity compared to the two other RhE models in catch-up
[42][43][44]
validation studies .
6.1, first paragraph
Replace the paragraph with the following paragraphs:
ISO 10993-23:2021/Amd.1:2025(en)
The in vitro method with RhE models for testing irritation was developed specifically to detect skin
[3][12]
irritation potential for neat chemicals (see OECD 439). The method was adapted and validated with
[5][6][12][13][17][18][19].
two RhE models for detection of irritant chemicals in medical device extracts This
method was found equally sensitive to detect low concentrations of some strong irritants in extracts
from polymeric medical materials (PVC and silicone) when compared to the human patch testing and
[14]
intracutaneous rabbit test . Hence, the RhE test as described in this document can replace the in vivo
rabbit test for irritation by skin exposure and by intracutaneous (intradermal) administration.
Two new type RhE models listed in OECD 439 were adopted for medical devices in 2023 after
[42][43][44]
demonstrating equivalent predictive capacity in interlaboratory studies .
6.2.2, eight paragraph
Replace the paragraph with the following:
For known cases of test-compounds requiring specific controls, some chemicals can directly reduce
the MTT reagent (e.g. electrophiles, test articles with high pH), while other chemicals can directly
colour the tissue or the cells. Such test sample properties can only interfere if sufficient amounts of
the chemical are still present on the tissue at the end of the exposure period. In these cases, a special
procedure allowing the quantification of the “true” MTT reduction should be applied. A protocol for the
determination of possible interactions with MTT is provid
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