National foreword

This British Standard is the UK implementation of EN ISO 10993‑10:2023. It is identical to ISO 10993‑10:2021. It supersedes BS EN ISO 10993‑10:2013, which is withdrawn.

The UK participation in its preparation was entrusted to Technical Committee CH/194, Biological evaluation of medical devices.

A list of organizations represented on this committee can be obtained on request to its committee manager.

Contractual and legal considerations

This publication has been prepared in good faith, however no representation, warranty, assurance or undertaking (express or implied) is or will be made, and no responsibility or liability is or will be accepted by BSI in relation to the adequacy, accuracy, completeness or reasonableness of this publication. All and any such responsibility and liability is expressly disclaimed to the full extent permitted by the law.

This publication is provided as is, and is to be used at the recipient’s own risk.

The recipient is advised to consider seeking professional guidance with respect to its use of this publication.

This publication is not intended to constitute a contract. Users are responsible for its correct application.

This publication has been prepared under a mandate given to the European Standards Organizations by the European Commission and the European Free Trade Association. It is intended to support requirements of the EU legislation detailed in the European Foreword. A European Annex, usually Annex ZA or ZZ, describes how this publication relates to that EU legislation.

For the Great Britain market (England, Scotland and Wales), if UK Government has designated this publication for conformity with UKCA marking (or similar) legislation, it may contain an additional National Annex. Where such a National Annex exists, it shows the correlation between this publication and the relevant UK legislation. If there is no National Annex of this kind, the relevant Annex ZA or ZZ in the body of the European text will indicate the relationship to UK regulation applicable in Great Britain. References to EU legislation may need to be read in accordance with the UK designation and the applicable UK law. Further information on designated standards can be found at

www.bsigroup.com/standardsandregulation.

For the Northern Ireland market, UK law will continue to implement relevant EU law subject to periodic confirmation. Therefore Annex ZA/ZZ in the European text, and references to EU legislation, are still valid for this market.

UK Government is responsible for legislation. For information on legislation and policies relating to that legislation, consult the relevant pages of www.gov.uk.

Compliance with a British Standard cannot confer immunity from legal obligations.

This British Standard was published under the authority of the Standards Policy and Strategy Committee on 28 February 2023.

Foreword

ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO member bodies). The work of preparing International Standards is normally carried out through ISO technical committees. Each member body interested in a subject for which a technical committee has been established has the right to be represented on that committee. International organizations, governmental and non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.

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 of ISO documents should be noted. This document was drafted in accordance with the editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).

Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of any patent rights identified during the development of the document will be in the Introduction and/or on the ISO list of patent declarations received (see www.iso.org/patents).

Any trade name used in this document is information given for the convenience of users and does not constitute an endorsement.

For an explanation on the voluntary nature of standards, the meaning of ISO specific terms and expressions related to conformity assessment, as well as information about ISO's adherence to the World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see the following URL: www.iso.org/iso/foreword.html.

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).

This fourth edition cancels and replaces the third edition ( ISO 10993‑10:2010), which has been technically revised.

The main changes compared to the previous edition are as follows:

this document now contains a description of skin sensitization testing only;
Annex C on non-animal methods for skin sensitization (formerly Annex D) has been updated;
the testing for irritation is now described in ISO 10993‑23.

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.

Introduction

This document assesses possible contact hazards from chemicals released from medical devices, which may produce skin sensitization.

Some materials that are included in medical devices have been tested, and their skin sensitization potential has been documented. Especially for dental materials, sensitizing properties were reported —see Reference [51]. Other materials and their chemical components have not been tested and may induce adverse effects when in contact with human tissue. The manufacturer is thus obliged to evaluate each device for potential adverse effects prior to marketing.

Traditionally, small animal tests are performed prior to testing on humans to help predict human response (background information is provided in Annex D). Since 2015, several in chemico and in vitro assays have been validated and Organization for Economic Co-operation and Development (OECD) test guidelines released to assess the skin sentization potential of chemicals.^[⁷⁵^][⁷⁹^][¹⁰⁴^] An overview of available alternative skin sensitization tests for neat chemicals is given in Annex C. These test methods, each developed to address a specific key event, can possibly not be sufficient alone to conclude on the presence or absence of skin sensitization potential of chemicals and should be considered in the context of integrated approaches such as integrated approaches to testing and assessment (IATA), combining them with other complementary information. Note that the in vitro and in chemico tests for skin sensitization in Annex C have thus far been validated only for neat chemicals and not for medical devices. To confirm that they are applicable for evaluation of the skin sensitization potential of medical devices, their assays need to be assessed and validated.

Where appropriate, the preliminary use of in vitro methods is encouraged for screening purposes prior to animal testing. To reduce the number of animals used, this document presents a step-wise approach, with review and analysis of test results at each stage. It is intended that, for regulatory submission, skin sensitization studies be conducted using GLP or ISO/IEC 17025 as applicable to the respective country and comply with regulations related to animal welfare. Statistical analyses of data are recommended and used whenever appropriate. This document includes important tools for the development of safe products and is intended for use by professionals, appropriately qualified by training and experience, who can interpret its requirements and judge the outcomes of the evaluation for each medical device, taking into consideration all the factors relevant to the device, its intended use and the current knowledge of the medical device provided by review of the scientific literature and previous clinical experience.

This document is based on numerous standards and guidelines, including OECD Guidelines, US Pharmacopoeia and the European Pharmacopoeia. It is intended to be the basic document for the selection and conduct of tests enabling the evaluation of dermal sensitization responses relevant to the safety of medical materials and devices.

This European Standard was approved by CEN on 13 September 2021.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN member.

This European Standard exists in three official versions (English, French, German). A version in any other language made by translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management Centre has the same status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Türkiye and United Kingdom.

European foreword

This document (EN ISO 10993‑10:2023) has been prepared by Technical Committee ISO/TC 194 "Biological and clinical evaluation of medical devices" in collaboration with Technical Committee CEN/TC 206 “Biological and clinical evaluation of medical devices” the secretariat of which is held by DIN.

This European Standard shall be given the status of a national standard, either by publication of an identical text or by endorsement, at the latest by August 2023, and conflicting national standards shall be withdrawn at the latest by August 2023.

Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. CEN shall not be held responsible for identifying any or all such patent rights.

This document supersedes EN ISO 10993‑10:2010.

This document has been prepared under a Standardization Request given to CEN by the European Commission and the European Free Trade Association, and supports essential requirements of EU Directive(s) / Regulation(s).

For the relationship with EU Directive(s) / Regulation(s), see informative Annex ZA, which is an integral part of this document.

Any feedback and questions on this document should be directed to the users’ national standards body/national committee. A complete listing of these bodies can be found on the CEN website.

According to the CEN-CENELEC Internal Regulations, the national standards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Türkiye and the United Kingdom.

Endorsement notice

The text of ISO 10993‑10:2021 has been approved by CEN as EN ISO 10993‑10:2023 without any modification.

1 Scope

This document specifies the procedure for the assessment of medical devices and their constituent materials with regard to their potential to induce skin sensitization.

This document includes:

details of in vivo skin sensitization test procedures;
key factors for the interpretation of the results.

NOTE Instructions for the preparation of materials specifically in relation to the above tests are given in Annex A.

2 Normative references

3 Terms and definitions

4 General principles — Step-wise approach

5 Pretest considerations

5.1 General

5.2 Types of material

5.3 Information on chemical composition

6 Skin sensitization tests

6.1 Choice of test methods

6.2 Murine local lymph node assay

6.3 Guinea pig assays for the detection of skin sensitization

6.4 Important factors affecting the outcome of the test

6.5 Guinea pig maximization test

6.6 Closed-patch test (Buehler test)

7 Key factors in interpretation of test results

Bibliography

BS EN ISO 10993-10:2023

Biological evaluation of medical devices - Tests for skin sensitization

Current

Published:

28 Feb 2023