EN ISO 10993-9:2009

Biological evaluation of medical devices - Part 9: Framework for identification and quantification of potential degradation products (ISO 10993-9:1999)

This part of ISO 10993 provides general principles for the systematic evaluation of the potential and observed biodegradation of medical devices and for the design and performance of biodegradation studies. This part of ISO 10993 is not applicable to: a) viable-tissue engineered products; b) methodologies for the generation of degradation products by mechanical processes. Methodologies for the production of this type of degradation product are described in specific product standards, where available; c) leachable components which are not degradation products. Where product standards provide applicable product-specific methodologies for the identification and quantification of degradation products, those standards shall be considered as alternatives.

Biologische Beurteilung von Medizinprodukten - Teil 9: Rahmen zur Identifizierung und Quantifizierung von möglichen Abbauprodukten (ISO 10993-9:1999)

Évaluation biologique des dispositifs médicaux - Partie 9: Cadre pour l'identification et la quantification des produits potentiels de dégradation (ISO 10993-9:1999)

Biološko ovrednotenje medicinskih pripomočkov - 9. del: Okvirni sistem za prepoznavanje in ugotavljanje količine morebitnih razgradnih produktov (ISO 10993-9:1999)

General Information

• Status: Withdrawn
• Publication Date: 19-May-2009
• Withdrawal Date: 14-Dec-2009
• ICS: 11.100 - Laboratory medicine
• ICS: 11.100.20 - Biological evaluation of medical devices
• Technical Committee: CEN/TC 206 - Biocompatibility of medical and dental materials and devices
• Drafting Committee: CEN/TC 206 - Biocompatibility of medical and dental materials and devices
• Current Stage: 9960 - Withdrawal effective - Withdrawal
• Due Date: 15-Dec-2009
• Completion Date: 15-Dec-2009
• Mandate: M/BC/CEN/89/9 - Joint Standardization request to CEN/CENELEC concerning harmonized standards relating to horizontal aspects in the field of medical devices
• Ref Project: SIST EN ISO 10993-9:2009 - Biological evaluation of medical devices - Part 9: Framework for identification and quantification of potential degradation products (ISO 10993-9:1999)

Standards Content (Sample)

SLOVENSKI STANDARD
SIST EN ISO 10993-9:2009
01-september-2009
1DGRPHãþD
SIST EN ISO 10993-9:2000
%LRORãNRRYUHGQRWHQMHPHGLFLQVNLKSULSRPRþNRYGHO2NYLUQLVLVWHP]D
SUHSR]QDYDQMHLQXJRWDYOMDQMHNROLþLQHPRUHELWQLKUD]JUDGQLKSURGXNWRY,62

Biological evaluation of medical devices - Part 9: Framework for identification and
quantification of potential degradation products (ISO 10993-9:1999)
Biologische Beurteilung von Medizinprodukten - Teil 9: Rahmen zur Identifizierung und
Quantifizierung von möglichen Abbauprodukten (ISO 10993-9:1999)
Évaluation biologique des dispositifs médicaux - Partie 9: Cadre pour l'identification et la
quantification des produits potentiels de dégradation (ISO 10993-9:1999)
Ta slovenski standard je istoveten z: EN ISO 10993-9:2009
ICS:
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
SIST EN ISO 10993-9:2009 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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SIST EN ISO 10993-9:2009

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SIST EN ISO 10993-9:2009
EUROPEAN STANDARD
EN ISO 10993-9
NORME EUROPÉENNE
EUROPÄISCHE NORM
May 2009
ICS 11.100.20 Supersedes EN ISO 10993-9:1999
English Version
Biological evaluation of medical devices - Part 9: Framework for
identification and quantification of potential degradation products
(ISO 10993-9:1999)
Évaluation biologique des dispositifs médicaux - Partie 9: Biologische Beurteilung von Medizinprodukten - Teil 9:
Cadre pour l'identification et la quantification des produits Rahmen zur Identifizierung und Quantifizierung von
potentiels de dégradation (ISO 10993-9:1999) möglichen Abbauprodukten (ISO 10993-9:1999)
This European Standard was approved by CEN on 28 April 2009.
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 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 Management Centre has the same status as the
official versions.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal,
Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2009 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 10993-9:2009: E
worldwide for CEN national Members.

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SIST EN ISO 10993-9:2009
EN ISO 10993-9:2009 (E)
Contents Page
Foreword .3
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on Medical Devices . Error! Bookmark not defined.
Annex ZB (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices .5

2

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SIST EN ISO 10993-9:2009
EN ISO 10993-9:2009 (E)
Foreword
The text of ISO 10993-9:1999 has been prepared by Technical Committee ISO/TC 194 “Biological evaluation
of medical devices” of the International Organization for Standardization (ISO) and has been taken over as EN
ISO 10993-9:2009 by Technical Committee CEN/TC 206 “Biological evaluation of medical devices” the
secretariat of which is held by NEN.
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 November 2009, and conflicting national standards shall be withdrawn
at the latest by March 2010.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 10993-9:1999.
This document has been prepared under a mandate given to CEN by the European Commission and the
European Free Trade Association, and supports essential requirements of EU Directives 93/42/EEC on
Medical Devices and 90/385/EEC on Active Implantable Medical Devices.
For relationship with EU Directives, see informative Annex ZA and ZB, which is an integral part of this
document.
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, Cyprus, Czech
Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia,
Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain,
Sweden, Switzerland and the United Kingdom.
Endorsement notice
The text of ISO 10993-9:1999 has been approved by CEN as a EN ISO 10993-9:2009 without any
modification.
3

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SIST EN ISO 10993-9:2009
EN ISO 10993-9:2009 (E)
Annex ZA
(informative)

Relationship between this European Standard and the Essential Requirements of
EU Directive 93/42/EEC on Medical Devices

This European Standard has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association to provide a means of conforming to Essential Requirements of the
New Approach Directive 93/42/EEC on medical devices.
Once this standard is cited in the Official Journal of the European Communities under that Directive and has
been implemented as a national standard in at least one Member State, compliance with the clauses of this
standard given in table ZA confers, within the limits of the scope of this standard, a presumption of conformity
with the corresponding Essential Requirements of that Directive and associated EFTA regulations.
Table ZA — Correspondence between this European Standard and Directive 93/42/EEC on medical
devices
Clause(s)/sub-clause(s) of this Essential Requirements (ERs) of Qualifying remarks/Notes
EN Directive 93/42/EEC
4, 5, & Annex A
Annex I:
7.1, 7.2, 7.5


WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling within
the scope of this standard.

4

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SIST EN ISO 10993-9:2009
EN ISO 10993-9:2009 (E)
Annex ZB
(informative)

Relationship between this European Standard and the Essential Requirements of
EU Directive 90/385/EEC on Active Implantable Medical Devices
This European Standard has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association to provide a means of conforming to Essential Requirements of the
New Approach Directive 90/385/EEC on active implantable medical devices.
Once this standard is cited in the Official Journal of the European Communities under that Directive and has
been implemented as a national standard in at least one Member State, compliance with the clauses of this
standard given in table ZB confers, within the limits of the scope of this standard, a presumption of conformity
with the corresponding Essential Requirements of that Directive and associated EFTA regulations.

Table ZB — Correspondence between this European Standard and Directive 90/385/EEC on active
implantable medical devices
Clause(s)/sub-clause(s) of this Essential Requirements (ERs) of Qualifying remarks/Notes
EN Directive 90/385/EEC
4, 5, Annex A
Annex I : The test methods do not include
pass/fail criteria
9

WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling within
the scope of this standard.
5

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SIST EN ISO 10993-9:2009

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SIST EN ISO 10993-9:2009
INTERNATIONAL ISO
STANDARD 10993-9
First edition
1999-03-01
Biological evaluation of medical devices —
Part 9:
Framework for identification and quantification
of potential degradation products
Évaluation biologique des dispositifs médicaux —
Partie 9: Cadre pour l'identification et la quantification des produits
potentiels de dégradation
A
Reference number
ISO/FDIS 10993-9:1999(E)

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SIST EN ISO 10993-9:2009
ISO 10993-9:1999(E)
Contents
Page
1 Scope .1
2 Normative references .1
3 Terms and definitions .1
4 Principles for design of degradation studies.2
4.1 General.2
4.2 Preliminary considerations.2
4.3 Study design .3
4.4 Characterization of degradation products from medical devices .3
5 Study report.3
Annex A (normative) Consideration of the need for degradation studies .5
Annex B (informative) Biodegradation study considerations .6
Bibliography.8
©  ISO 1999
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means, electronic
or mechanical, including photocopying and microfilm, without permission in writing from the publisher.
International Organization for Standardization
Case postale 56 • CH-1211 Genève 20 • Switzerland
Internet [e-mail]
Printed in Switzerland
ii

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SIST EN ISO 10993-9:2009
©
ISO ISO 10993-9:1999(E)
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.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 3.
Draft International Standards adopted by the technical committees are circulated to the member bodies for voting.
Publication as an International Standard requires approval by at least 75 % of the member bodies casting a vote.
International Standard ISO 10993-9 was prepared by Technical Committee ISO/TC 194, Biological evaluation of
medical devices.
This first edition cancels and replaces the first edition of ISO/TR 10993-9:1994, which has been technically revised.
ISO 10993 consists of the following parts, under the general title Biological evaluation of medical devices:
 Part 1: Evaluation and testing
 Part 2: Animal welfare requirements
 Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity
 Part 4: Selection of tests for interactions with blood
 Part 5: Tests for in vitro cytotoxicity
 Part 6: Tests for local effects after implantation
 Part 7: Ethylene oxide sterilization residuals
 Part 9: Framework for the identification and quantification of potential degradation products
 Part 10: Tests for irritation and sensitization
 Part 11: Tests for systemic toxicity
 Part 12: Sample preparation and reference materials
 Part 13: Identification and quantification of degradation products from polymers
 Part 14: Identification and quantification of degradation products from ceramics
 Part 15: Identification and quantification of degradation products from metals and alloys
 Part 16: Toxicokinetic study design for degradation products and leachables
 Part 18: Chemical characterization.
Further parts will deal with other relevant aspects of biological testing.
Annex A forms a normative part of this part of ISO 10993. Annex B is for information only.
iii

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SIST EN ISO 10993-9:2009
©
ISO 10993-9:1999(E) ISO
Introduction
This part of 10993 is inte
...

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.Biologische Beurteilung von Medizinprodukten - Teil 9: Rahmen zur Identifizierung und Quantifizierung von möglichen Abbauprodukten (ISO 10993-9:1999)Évaluation biologique des dispositifs médicaux - Partie 9: Cadre pour l'identification et la quantification des produits potentiels de dégradation (ISO 10993-9:1999)Biological evaluation of medical devices - Part 9: Framework for identification and quantification of potential degradation products (ISO 10993-9:1999)11.100.20Biological evaluation of medical devicesICS:Ta slovenski standard je istoveten z:prEN ISO 10993-9kSIST prEN ISO 10993-9:2009en01-marec-2009kSIST prEN ISO 10993-9:2009SLOVENSKI
STANDARD



kSIST prEN ISO 10993-9:2009



EUROPEAN STANDARDNORME EUROPÉENNEEUROPÄISCHE NORMFINAL DRAFTprEN ISO 10993-9November 2008ICS 11.100.20Will supersede EN ISO 10993-9:1999
English VersionBiological evaluation of medical devices - Part 9: Framework foridentification and quantification of potential degradation products(ISO 10993-9:1999)Évaluation biologique des dispositifs médicaux - Partie 9:Cadre pour l'identification et la quantification des produitspotentiels de dégradation (ISO 10993-9:1999)Biologische Beurteilung von Medizinprodukten - Teil 9:Rahmen zur Identifizierung und Quantifizierung vonmöglichen Abbauprodukten (ISO 10993-9:1999)This draft European Standard is submitted to CEN members for unique acceptance procedure. It has been drawn up by the TechnicalCommittee CEN/TC 206.If this draft becomes a European Standard, CEN members are bound to comply with the CEN/CENELEC Internal Regulations whichstipulate the conditions for giving this European Standard the status of a national standard without any alteration.This draft European Standard was established by CEN in three official versions (English, French, German). A version in any other languagemade by translation under the responsibility of a CEN member into its own language and notified to the CEN Management Centre has thesame status as the official versions.CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland,France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal,Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.Warning : This document is not a European Standard. It is distributed for review and comments. It is subject to change without notice andshall not be referred to as a European Standard.EUROPEAN COMMITTEE FOR STANDARDIZATIONCOMITÉ EUROPÉEN DE NORMALISATIONEUROPÄISCHES KOMITEE FÜR NORMUNGManagement Centre: rue de Stassart, 36
B-1050 Brussels© 2008 CENAll rights of exploitation in any form and by any means reservedworldwide for CEN national Members.Ref. No. prEN ISO 10993-9:2008: EkSIST prEN ISO 10993-9:2009



prEN ISO 10993-9:2008 (E) 2 Contents Page Foreword .3Annex ZA (informative)
Relationship between this
European
Standard and the Essential Requirements
of EU Directive 93/42/EEC on Medical Devices .4Annex ZB (informative)
Relationship between this
European
Standard and the Essential Requirements
of EU Directive 90/385/EEC on Active Implantable Medical Devices .5 kSIST prEN ISO 10993-9:2009



prEN ISO 10993-9:2008 (E) 3 Foreword The text of ISO 10993-9:1999 has been prepared by Technical Committee ISO/TC 194 “Biological evaluation of medical devices” of the International Organization for Standardization (ISO) and has been taken over as prEN ISO 10993-9:2008 by Technical Committee CEN/TC 206 “Biological evaluation of medical devices” the secretariat of which is held by NEN. This document is currently submitted to the Unique Acceptance Procedure. This document will supersede EN ISO 10993-9:1999. This document has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association, and supports essential requirements of EU Directives 93/42/EEC on Medical Devices and 90/385/EEC on Active Implantable Medical Devices. For relationship with EU Directives, see informative Annex ZA and ZB, which is an integral part of this document. Endorsement notice The text of ISO 10993-9:1999 has been approved by CEN as a prEN ISO 10993-9:2008 without any modification. kSIST prEN ISO 10993-9:2009



prEN ISO 10993-9:2008 (E) 4 Annex ZA (informative)
Relationship between this
European
Standard and the Essential Requirements
of EU Directive 93/42/EEC on Medical Devices
This European Standard has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association to provide a means of conforming to Essential Requirements of the New Approach Directive 93/42/EEC on medical devices. Once this standard is cited in the Official Journal of the European Communities under that Directive and has been implemented as a national standard in at least one Member State, compliance with the clauses of this standard given in table ZA confers, within the limits of the scope of this standard, a presumption of conformity with the corresponding Essential Requirements of that Directive and associated EFTA regulations. Table ZA — Correspondence between this European Standard and Directive 93/42/EEC on medical devices Clause(s)/sub-clause(s) of this EN Essential Requirements (ERs) of Directive 93/42/EEC Qualifying remarks/Notes 4, 5, & Annex A
Annex I: 7.1, 7.2, 7.5
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling within the scope of this standard.
kSIST prEN ISO 10993-9:2009



prEN ISO 10993-9:2008 (E) 5 Annex ZB (informative)
Relationship between this
European
Standard and the Essential Requirements
of EU Directive 90/385/EEC on Active Implantable Medical Devices This European Standard has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association to provide a means of conforming to Essential Requirements of the New Approach Directive 90/385/EEC on active implantable medical devices. Once this standard is cited in the Official Journal of the European Communities under that Directive and has been implemented as a national standard in at least one Member State, compliance with the clauses of this standard given in table ZB confers, within the limits of the scope of this standard, a presumption of conformity with the corresponding Essential Requirements of that Directive and associated EFTA regulations.
Table ZB — Correspondence between this European Standard and Directive 90/385/EEC on active implantable medical devices Clause(s)/sub-clause(s) of this EN Essential Requirements (ERs) of Directive 90/385/EEC Qualifying remarks/Notes 4, 5, Annex A Annex I : 9 The test methods do not include pass/fail criteria
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling within the scope of this standard. kSIST prEN ISO 10993-9:2009



kSIST prEN ISO 10993-9:2009



AReference numberISO/FDIS 10993-9:1999(E)INTERNATIONALSTANDARDISO10993-9First edition1999-03-01Biological evaluation of medical devices —Part 9:Framework for identification and quantificationof potential degradation productsÉvaluation biologique des dispositifs médicaux —Partie 9: Cadre pour l'identification et la quantification des produitspotentiels de dégradationkSIST prEN ISO 10993-9:2009



ISO 10993-9:1999(E)©
ISO 1999All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means, electronicor mechanical, including photocopying and microfilm, without permission in writing from the publisher.International Organization for StandardizationCase postale 56 · CH-1211 Genève 20 · [e-mail] in SwitzerlandiiContentsPage1 Scope.12 Normative references.13 Terms and definitions.14 Principles for design of degradation studies.24.1 General.24.2 Preliminary considerations.24.3 Study design.34.4 Characterization of degradation products from medical devices.35 Study report.3Annex A (normative)
Consideration of the need for degradation studies.5Annex B (informative)
Biodegradation study considerations.6Bibliography.8kSIST prEN ISO 10993-9:2009



© ISOISO 10993-9:1999(E)iiiForewordISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISOmember bodies). The work of preparing International Standards is normally carried out through ISO technicalcommittees. Each member body interested in a subject for which a technical committee has been established hasthe right to be represented on that committee. International organizations, governmental and non-governmental, inliaison with ISO, also take part in the work. ISO collaborates closely with the International ElectrotechnicalCommission (IEC) on all matters of electrotechnical standardization.International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 3.Draft International Standards adopted by the technical committees are circulated to the member bodies for voting.Publication as an International Standard requires approval by at least 75 % of the member bodies casting a vote.International Standard ISO 10993-9 was prepared by Technical Committee ISO/TC 194, Biological evaluation ofmedical devices.This first edition cancels and replaces the first edition of ISO/TR 10993-9:1994, which has been technically revised.ISO 10993 consists of the following parts, under the general title Biological evaluation of medical devices:¾ Part 1:
Evaluation and testing¾ Part 2:
Animal welfare requirements¾ Part 3:
Tests for genotoxicity, carcinogenicity and reproductive toxicity¾ Part 4:
Selection of tests for interactions with blood¾ Part 5:
Tests for in vitro cytotoxicity¾ Part 6:
Tests for local effects after implantation¾ Part 7:
Ethylene oxide sterilization residuals¾ Part 9:
Framework for the identification and quantification of potential degradation products¾ Part 10:
Tests for irritation and sensitization¾ Part 11:
Tests for systemic toxicity¾ Part 12:
Sample preparation and reference materials¾ Part 13:
Identification and quantification of degradation products from polymers¾ Part 14:
Identification and quantification of degradation products from ceramics¾ Part 15:
Identification and quantification of degradation products from metals and alloys¾ Part 16:
Toxicokinetic study design for degradation products and leachables¾ Part 18:
Chemical characterization.Further parts will deal with other relevant aspects of biological testing.Annex A forms a normative part of this part of ISO 10993. Annex B is for information only.kSIST prEN ISO 10993-9:2009



ISO 10993-9:1999(E)© ISOivIntroductionThis part of 10993 is intended to present the general principles on which the specific material investigations toidentify and quantify degradation products described in ISO 10993-13 (polymers), ISO 10993-14 (ceramics) andISO 10993-15 (metals and alloys) are based.Information obtained from these studies is intended to be used in the biological evaluations described in theremaining parts of ISO 10993.The materials used to construct medical devices may form degradation products when exposed to the biologicalenvironment, and these products m
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