ISO/TS 11796:2023

TECHNICAL ISO/TS
SPECIFICATION 11796
First edition
2023-07
Biological evaluation of medical
devices — Requirements for
interlaboratory studies to
demonstrate the applicability of
validated in vitro methods to assess
the skin sensitization of medical
devices
Évaluation biologique des dispositifs médicaux — Guide pour les
études interlaboratoires visant à démontrer l'applicabilité des
méthodes in-vitro validées pour évaluer la sensibilisation cutanée des
dispositifs médicaux
Reference number
© ISO 2023
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ii
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Consideration on the process for demonstration of the applicability domain .3
5 Positive and negative control test samples . 4
5.1 General . 4
5.2 Database of reference chemicals . 5
5.3 Reference materials . 8
5.3.1 General . 8
5.3.2 Negative control medical device material . 8
5.3.3 Positive reference material . 8
6 Preparation of the test samples .9
6.1 General . 9
6.2 Preparation of the extracts . 9
6.3 Spiking of the extracts . 9
7 Prevalidation of candidate test methods .10
8 Interlaboratory study .10
8.1 General . 10
8.2 Study organization . 10
8.2.1 General . 10
8.2.2 Management team . 11
8.2.3 Lead laboratory . 11
8.2.4 Sample management . 11
8.2.5 Independent biostatistician . 11
8.3 Sample preparation . 11
8.4 Performance review .12
9 Statistical analysis .12
10 Test report .12
Annex A (normative) Reference chemicals .14
Bibliography .29
iii
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
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electrotechnical standardization.
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This document was prepared by Technical Committee ISO/TC 194, Biological and clinical evaluation of
medical devices.
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iv
Introduction
International Standards can be used to demonstrate the safety and compliance of medical devices.
ISO 10993-10 specifies the procedure for the assessment of medical devices and their constituent
materials with regard to their potential to induce skin sensitization (Type IV hypersensitivity reaction).
The methods included in ISO 10993-10 are based on animal or human testing, with an annex on in vitro
and in chemico tests for skin sensitization that have been validated for neat chemicals. The effort to
reduce or replace the use of animals in toxicity testing has led to the development of many new non-
animal methods. The test guidelines in References [56] and [57] include alternatives to animal testing
methods for skin sensitization that have been previously validated to confirm their equivalence/
superiority to the current in vivo methods. However, currently, none of the OECD test guideline methods
are considered sufficient stand-alone replacements for in vivo tests that assess the skin sensitization
[1]
potential of chemicals .
Current OECD test guideline methods are validated with neat chemicals and not with more complex
mixtures such as medical devices or medical devices extracts. In order to use these methods in the
specific context of medical devices, an evaluation is needed to verify their applicability for assessing
skin sensitization of medical devices. Given the number of candidate test methods and the time that
is required to assess them, it is important to ensure that the same science-based evaluation process
and criteria are consistently applied to any new candidate test method. The purpose of this document
is to provide a framework for the conduct of prevalidation and interlaboratory studies to assess the
applicability of candidate test methods for assessing one or more key events related to OECD’s adverse
[2]
outcome pathway (AOP) for skin sensitization when evaluating medical devices .
v
TECHNICAL SPECIFICATION ISO/TS 11796:2023(E)
Biological evaluation of medical devices — Requirements
for interlaboratory studies to demonstrate the
applicability of validated in vitro methods to assess the
skin sensitization of medical devices
1 Scope
This document specifies the framework and the methodology to evaluate and demonstrate the
applicability of a validated non-animal method from an OECD test guideline to assess the skin sensitizing
potential of a medical device or a medical device material. This document addresses:
— the database of reference chemical skin sensitizers and non-skin sensitizers;
— reference materials;
— feasibility testing of candidate test methods, including any method optimization for use with
extracts of medical devices;
— prevalidation of candidate test methods;
— the interlaboratory study:
— sample preparation and coding;
— spiking of the extracts from the negative control medical device material;
— data collection;
— statistical analysis to assess reliability and reproducibility.
The use of the approaches described in this document to assess the applicability of a candidate test
method does not imply that the candidate test method can be used as a stand-alone test for evaluating
the skin sensitization potential of medical devices. For certain candidate test methods, integrated
[1]
approaches and/or defined approaches are needed. The evaluation of skin sensitization potential of a
medical device is described in ISO 10993-10.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements of this document. For dated references, only the edition cited applies. For
undated references, the latest edition of the referenced document (including any amendments) applies.
ISO 10993-12, Biological evaluation of medical devices — Part 12: Sample preparation and reference
materials
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1
allergen
sensitizer
substance or material that is capable of inducing a specific hypersensitivity reaction upon repeated
contact with that substance or material
3.2
candidate test method
test method for in vitro skin sensitiz
...