SIST EN ISO 10993-23:2021/oprA1:2024
(Amendment)Biological evaluation of medical devices - Part 23: Tests for irritation - Amendment 1: Additional in vitro reconstructed human epidermis models (ISO 10993-23:2021/DAmd1:2024)
Biological evaluation of medical devices - Part 23: Tests for irritation - Amendment 1: Additional in vitro reconstructed human epidermis models (ISO 10993-23:2021/DAmd1:2024)
Biologische Beurteilung von Medizinprodukten - Teil 23: Prüfungen auf Irritation - ÄNDERUNG 1 (ISO 10993 23:2021/DAmd1:2024)
Évaluation biologique des dispositifs médicaux - Partie 23: Essais d'irritation - Amendement 1: Modèles supplémentaires d'épiderme humain reconstruit in vitro (ISO 10993-23:2021/DAmd1:2024)
Biološko ovrednotenje medicinskih pripomočkov - 23. del: Preskusi draženja - Dopolnilo A1: Dodatni in vitro modeli rekonstruirane človeške povrhnjice (ISO 10993-23:2021/DAmd1:2024)
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SLOVENSKI STANDARD
01-november-2024
Biološko ovrednotenje medicinskih pripomočkov - 23. del: Preskusi draženja -
Dopolnilo A1: Dodatni in vitro modeli rekonstruirane človeške povrhnjice (ISO
10993-23:2021/DAmd1:2024)
Biological evaluation of medical devices - Part 23: Tests for irritation - Amendment 1:
Additional in vitro reconstructed human epidermis models (ISO 10993-
23:2021/DAmd1:2024)
Biologische Beurteilung von Medizinprodukten - Teil 23: Prüfungen auf Irritation -
ÄNDERUNG 1 (ISO 10993 23:2021/DAmd1:2024)
Évaluation biologique des dispositifs médicaux - Partie 23: Essais d'irritation -
Amendement 1: Modèles supplémentaires d'épiderme humain reconstruit in vitro (ISO
10993-23:2021/DAmd1:2024)
Ta slovenski standard je istoveten z: EN ISO 10993-23:2021/prA1
ICS:
11.100.20 Biološko ovrednotenje Biological evaluation of
medicinskih pripomočkov medical devices
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
DRAFT
Amendment
ISO 10993-23:2021/
DAM 1
ISO/TC 194
Biological evaluation of medical
Secretariat: DIN
devices —
Voting begins on:
Part 23:
2024-09-25
Tests for irritation
Voting terminates on:
2024-12-18
AMENDMENT 1: Additional in vitro
reconstructed human epidermis
models
ICS: 11.100.20
THIS DOCUMENT IS A DRAFT CIRCULATED
FOR COMMENTS AND APPROVAL. IT
IS THEREFORE SUBJECT TO CHANGE
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This document is circulated as received from the committee secretariat.
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Reference number
ISO 10993-23:2021/DAM 1:2024(en)
DRAFT
ISO 10993-23:2021/DAM 1:2024(en)
Amendment
ISO 10993-23:2021/
DAM 1
ISO/TC 194
Biological evaluation of medical
Secretariat: DIN
devices —
Voting begins on:
Part 23:
Tests for irritation
Voting terminates on:
AMENDMENT 1: Additional in vitro
reconstructed human epidermis
models
ICS: 11.100.20
THIS DOCUMENT IS A DRAFT CIRCULATED
FOR COMMENTS AND APPROVAL. IT
IS THEREFORE SUBJECT TO CHANGE
AND MAY NOT BE REFERRED TO AS AN
INTERNATIONAL STANDARD UNTIL
PUBLISHED AS SUCH.
This document is circulated as received from the committee secretariat.
IN ADDITION TO THEIR EVALUATION AS
BEING ACCEPTABLE FOR INDUSTRIAL,
© ISO 2024
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
STANDARDS MAY ON OCCASION HAVE TO
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Published in Switzerland Reference number
ISO 10993-23:2021/DAM 1:2024(en)
ii
ISO 10993-23:2021/DAM 1:2024(en)
Foreword
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The procedures used to develop this document and those intended for its further maintenance are described
in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the different types
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Amendment 1 to ISO 10993-23:2021 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, Biocompatibility of medical and dental materials and devices, in
accordance with the Agreement on technical cooperation between ISO and CEN (Vienna Agreement).
This amendment to ISO 10993-23:2021 refines the following:
— Addition of two reconstructed human epidermis (RhE) models to the list of models accepted to conduct
in vitro alternative test per the methods in 6.2 to 6.12;
— Clause 6 updated to introduce specificities of the two RhE models added.
A list of all parts in the ISO 10993 series can be found on the ISO website.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www.iso.org/members.html.
iii
ISO 10993-23:2021/DAM 1:2024(en)
Biological evaluation of medical devices —
Part 23:
Tests for irritation
AMENDMENT 1: Additional in vitro reconstructed human
epidermis models
Page vi, Introduction, fifth paragraph
Replace the paragraph with the following:
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 round robin 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 round robin
[42][45]
studies .
Page 4, clause 4, second paragraph
Replace the paragraph with the following:
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 round
robin 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][45]
validation studies .
Page 6, 6.1, first paragraph
ISO 10993-23:2021/DAM 1:2024(en)
Replace the paragraph with the following:
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][45]
demonstrating equivalent predictive capacity in catch-up validation studies .
Page 7, 6.2.2, eight paragraph
Replace the paragraph with the following:
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 provided in References [20], [21], [43] and [44]. The use of specific and
adapted controls enables the calculation of true tissue viability after subtracting the unspecific optical
densities (OD) due to direct chemical MTT reduction or chemical residual colour extracted from the
tissues, or both.
Page 8, 6.3.1, second paragraph
Add the following sentence at the end of the paragraph:
3 4
Two new additional RhE models, KeraSkin™ RhE and LabCyte EPI-MODEL24 RhE were evaluated
[42][45]
in a same method as the international round robin study . Specific protocol is available as
[43] [44]
supplementary material .
Add the following footnotes:
KeraSkin™ is a trademark of a product supplied by Biosolution Co. Ltd. (Seoul, Korea). This information
is given for the convenience of users of this document and does not constitute an endorsement by ISO of
the product named. Equivalent products may be used if they can be shown to lead to the same results.
LabCyte EPI-MODEL24 is a product supplied by Japan Tissue Engineering Co. Ltd. (Aichi, Japan).
This information is given for the convenience of users of this document and does not constitute an
endorsement by ISO of the product named. Equivalent products may be used if they can be shown to
lead to the same results.
Page 8, 6.3.1, third paragraph
Replace the first sentence with the following:
These RhE models have been validated by EURL ECVAM for determining skin irritation of chemicals and
[41]
are included in OECD 439 and EU Guideline B.46 .
ISO 10993-23:2021/DAM 1:2024(en)
Page 10, 6.4.2, NOTE
Replace NOTE with the following:
NOTE In the round robin study the incubation time was (18 ± 1) h for EpiDerm™ tissues (EPI-200),
(24 ± 2) h for the SkinEthic™ RHE model, (18 ± 1) h for KeraSkin™ RhE and (18 ± 1) h for LabCyte
EPI-MODEL24. However, three models except for LabCyte EPI-MODEL24 show similar outcomes at either
[13][19][17][45]
18 h or 24 h exposure .
Page 12, 6.6.3, Test extract and controls exposure
Apply (100 ± 2) µl of the undiluted test samples (i.e. medical device extracts), VCs, NC or PC on the
surface of three single tissues each. Use the pipette tip to spread the test sample gently on the epidermis
topical surface. The application order is important since it has to be the same for washing.
Page 12, 6.6.3, NOTE 2
Add “1” to the first NOTE and replace NOTE 2 with the following:
NOTE 2 In the round robin study the incubation time was (18 ± 1) h for EpiDerm™ tissues EPI-
200 model and (24 ± 2) h for the SkinEthic™ RHE model, (18 ± 1) h for KeraSkin™ RhE and (18 ± 1) h for
LabCyte EPI-MODEL24.
Page 13, 6.7.1, after the second indent
Add a NOTE:
TM
...
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