SIST EN ISO 10993-15:2009
(Main)Biological evaluation of medical devices - Part 15: Identification and quantification of degradation products from metals and alloys (ISO 10993-15:2000)
Biological evaluation of medical devices - Part 15: Identification and quantification of degradation products from metals and alloys (ISO 10993-15:2000)
This part of ISO 10993 provides guidance on general requirements for the design of tests for identifying and quantifying degradation products from finished metallic medical devices or corresponding material samples finished as ready for clinical use. It is applicable only to those degradation products generated by chemical alteration of the finished metallic device in an in vitro accelerated degradation test. Because of the accelerated nature of these tests, the test results may not reflect the implant or material behavior in the body. The described chemical methodologies are a means to generate degradation products for further assessments. This part of ISO 10993 is not applicable to degradation products induced by applied mechanical stress.
Biologische Beurteilung von Medizinprodukten - Teil 15: Qualitativer und quantitativer Nachweis von Abbauprodukten aus Metallen und Legierungen (ISO 10993-15:2000)
Dieser Teil von ISO 10993 dient als Leitfaden der allgemeinen Anforderungen zur Konzeption von Prüfungen
für den qualitativen und quantitativen Nachweis von Abbauprodukten von fertigen Medizinprodukten aus
Metall oder entsprechenden Materialproben im Endzustand, die zur klinischen Anwendung bereit sind. Er ist
nur auf solche Abbauprodukte anwendbar, die durch eine chemische Veränderung des fertigen Metallproduktes
in einer beschleunigten in vitro-Prüfung erzeugt werden. Aufgrund der beschleunigten Natur dieser
Prüfung könnten die Prüfergebnisse das Verhalten des Implantats oder des Materials im Körper nicht richtig
wiedergeben. Die beschriebenen chemischen Verfahren sind ein Mittel, um Abbauprodukte für weitere Beurteilungen
zu erzeugen.
Dieser Teil von ISO 10993 gilt nicht für Abbauprodukte, die durch mechanische Belastungen erzeugt werden.
ANMERKUNG Mechanisch verursachter Abbau, wie zum Beispiel Verschleiß, kann in der jeweiligen produktspezifischen
Norm beschrieben werden. Sofern produktgruppenspezifische Normen anwendbare produktspezifische Verfahren
für den qualitativen und quantitativen Nachweis von Abbauprodukten enthalten, sollten diese berücksichtigt werden.
In Anbetracht des breiten Spektrums an metallischen Werkstoffen, die für Medizinprodukte verwendet werden,
werden keine spezifischen analytischen Verfahren zum quantitativen Nachweis der Abbauprodukte festgelegt.
Der Nachweis von Spurenelementen (< 106), die in bestimmten Metallen oder Legierungen vorhanden sind,
wird in diesem Teil von ISO 10993 nicht beschrieben. Ebenso legt dieser Teil von ISO 10993 keine spezifischen
Anforderungen für akzeptierbare Toleranzwerte von Abbauprodukten fest.
Dieser Teil von ISO 10993 beschreibt nicht die biologische Aktivität der Abbauprodukte; hierzu wird auf die
anwendbaren Abschnitte von ISO 10993-1 und ISO 10993-17 verwiesen.
Evaluation biologique des dispositifs médicaux - Partie 15: Identification et quantification des produits de dégradation issus des métaux et alliages (ISO 10993-15:2000)
La présente partie de l'ISO 10993 fournit les lignes directrices relatives aux exigences générales pour la conception des essais d'identification et de quantification des produits de dégradation issus de dispositifs médicaux métalliques finis ou d'échantillons des matériaux correspondants prêts pour une utilisation clinique. Elle ne s'applique qu'aux produits de dégradation créés par une modification chimique du dispositif métallique fini et au moyen d'un essai de dégradation in vitro accéléré. Il est possible que les résultats d'essai ne reflètent pas le comportement de l'implant ou du matériau dans le corps. En raison du caractère accéléré de ces essais, la méthodologie chimique décrite est un moyen de générer des produits de dégradation en vue d'analyses ultérieures. La présente partie de l'ISO 10993 ne s'applique pas aux produits de dégradation induite par l'application d'une contrainte mécanique.
NOTE La dégradation induite par une action mécanique, telle que l'usure, peut être couverte par une norme de produit spécifique appropriée. Si les normes de produit proposent des méthodologies applicables spécifiques au produit pour l'identification et la quantification des produits de dégradation, il convient de prendre en compte ces normes. En raison de la grande variété des matériaux métalliques utilisés dans la fabrication des dispositifs médicaux, la présente partie de l'ISO 10993 n'indique aucune technique d'analyse spécifique pour la quantification des produits de dégradation. La présente partie de l'ISO 10993 ne traite pas de l'identification d'éléments à l'état de trace (< 10-6) contenus dans le métal ou l'alliage analysé. Elle ne fournit aucune exigence spécifique relative aux niveaux admissibles de produits de dégradation.
Biološko ovrednotenje medicinskih pripomočkov - 15. del: Identifikacija in ugotavljanje količine razgradnih produktov iz kovin in zlitin (ISO 10993-15:2000)
General Information
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Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 10993-15:2009
01-september-2009
1DGRPHãþD
SIST EN ISO 10993-15:2001
%LRORãNRRYUHGQRWHQMHPHGLFLQVNLKSULSRPRþNRYGHO ,GHQWLILNDFLMDLQ
XJRWDYOMDQMHNROLþLQHUD]JUDGQLKSURGXNWRYL]NRYLQLQ]OLWLQ ,62
Biological evaluation of medical devices - Part 15: Identification and quantification of
degradation products from metals and alloys (ISO 10993-15:2000)
Biologische Beurteilung von Medizinprodukten - Teil 15: Qualitativer und quantitativer
Nachweis von Abbauprodukten aus Metallen und Legierungen (ISO 10993-15:2000)
Evaluation biologique des dispositifs médicaux - Partie 15: Identification et quantification
des produits de dégradation issus des métaux et alliages (ISO 10993-15:2000)
Ta slovenski standard je istoveten z: EN ISO 10993-15:2009
ICS:
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
SIST EN ISO 10993-15:2009 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 10993-15:2009
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SIST EN ISO 10993-15:2009
EUROPEAN STANDARD
EN ISO 10993-15
NORME EUROPÉENNE
EUROPÄISCHE NORM
June 2009
ICS 11.100.20 Supersedes EN ISO 10993-15:2000
English Version
Biological evaluation of medical devices - Part 15: Identification
and quantification of degradation products from metals and
alloys (ISO 10993-15:2000)
Évaluation biologique des dispositifs médicaux - Partie 15: Biologische Beurteilung von Medizinprodukten - Teil 15:
Identification et quantification des produits de dégradation Qualitativer und quantitativer Nachweis von
issus des métaux et alliages (ISO 10993-15:2000) Abbauprodukten aus Metallen und Legierungen (ISO
10993-15:2000)
This European Standard was approved by CEN on 23 May 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 10993-15:2009: E
worldwide for CEN national Members.
---------------------- Page: 3 ----------------------
SIST EN ISO 10993-15:2009
EN ISO 10993-15:2009 (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 .4
2
---------------------- Page: 4 ----------------------
SIST EN ISO 10993-15:2009
EN ISO 10993-15:2009 (E)
Foreword
The text of ISO 10993-15:2000 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 10993-15:2009 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 December 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 10993-15:2000.
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 Directive 93/42/EEC on
Medical Devices.
For relationship with the EU Directive, see informative Annex ZA, 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 10993-15:2000 has been approved by CEN as a EN ISO 10993-15:2009 without any
modification.
3
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SIST EN ISO 10993-15:2009
EN ISO 10993-15:2009 (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, 6, 7, 8, 9
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
---------------------- Page: 6 ----------------------
SIST EN ISO 10993-15:2009
INTERNATIONAL ISO
STANDARD 10993-15
First edition
2000-12-01
Corrected and reprinted
2001-04-01
Biological evaluation of medical devices —
Part 15:
Identification and quantification of
degradation products from metals and
alloys
Évaluation biologique des dispositifs médicaux —
Partie 15: Identification et quantification des produits de dégradation issus
des métaux et alliages
Reference number
ISO 10993-15:2000(E)
©
ISO 2000
---------------------- Page: 7 ----------------------
SIST EN ISO 10993-15:2009
ISO 10993-15:2000(E)
PDF disclaimer
This PDF file may contain embedded typefaces. In accordance with Adobe's licensing policy, this file may be printed or viewed but shall not
be edited unless the typefaces which are embedded are licensed to and installed on the computer performing the editing. In downloading this
file, parties accept therein the responsibility of not infringing Adobe's licensing policy. The ISO Central Secretariat accepts no liability in this
area.
Adobe is a trademark of Adobe Systems Incorporated.
Details of the software products used to create this PDF file can be found in the General Info relative to the file; the PDF-creation parameters
were optimized for printing. Every care has been taken to ensure that the file is suitable for use by ISO member bodies. In the unlikely event
that a problem relating to it is found, please inform the Central Secretariat at the address given below.
© ISO 2000
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 either ISO at the address below or ISO's member body
in the country of the requester.
ISO copyright office
Case postale 56 � CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail copyright@iso.ch
Web www.iso.ch
Printed in Switzerland
ii © ISO 2000 – All rights reserved
---------------------- Page: 8 ----------------------
SIST EN ISO 10993-15:2009
ISO 10993-15:2000(E)
Contents Page
Foreword.iv
Introduction.vi
1 Scope .1
2 Normative references .1
3 Terms and definitions .2
4 Degradation test methods .2
4.1 General.2
4.2 Prerequisites .3
5 Reagent and sample preparation.3
5.1 Sample documentation .3
5.2 Test solution (electrolyte) .3
5.3 Preparation of test samples.3
6 Electrochemical tests.4
6.1 Apparatus .4
6.2 Sample preparation .4
6.3 Test conditions .5
6.4 Potentiodynamic measurements .5
6.5 Potentiostatic measurements.5
7 Immersion test .5
7.1 Apparatus .5
7.2 Sample preparation .7
7.3 Immersion test procedure.7
8 Analysis .8
9 Test report .8
Annex A (informative) Schematic diagram of the electrochemical measuring circuit.9
Annex B (informative) Schematic drawing of an electrolytic cell .10
Annex C (informative) Examples of alternative electrolytes for the electrochemical tests.11
Bibliography.12
© ISO 2000 – All rights reserved iii
---------------------- Page: 9 ----------------------
SIST EN ISO 10993-15:2009
ISO 10993-15:2000(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.
Attention is drawn to the possibility that some of the elements of this part of ISO 10993 may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights.
International Standard ISO 10993-15 was prepared by Technical Committee ISO/TC 194, Biological evaluation of
medical devices.
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 8: Selection and qualification of reference materials for biological tests
� Part 9: Framework for identification and quantification of potential degradation products
� Part 10: Tests for irritation and delayed-type hypersensitiviy
� Part 11: Tests for systemic toxicity
� Part 12: Sample preparation and reference materials
� Part 13: Identification and quantification of degradation products from polymeric medical devices
� 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
iv © ISO 2000 – All rights reserved
---------------------- Page: 10 ----------------------
SIST EN ISO 10993-15:2009
ISO 10993-15:2000(E)
� Part 17: Establishment of allowable limits for leachable substances using health-based risk assessment
� Part 18: Chemical characterization of materials
Future parts will deal with other relevant aspects of biological testing.
Annexes A, B and C of this part of ISO 10993 are for information only.
© ISO 2000 – All rights reserved v
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SIST EN ISO 10993-15:2009
ISO 10993-15:2000(E)
Introduction
One of the potential health hazards resulting from medical devices may be due to the interactions of their
electrochemically-induced degradation products with the biological system. Therefore, the evaluation of potential
degradation products from metallic materials by methods suitable for testing the electrochemical behavior of these
materials is a necessary step in the biological performance testing of materials.
The body environment typically contains cations of sodium, potassium, calcium and magnesium and anions of
–3
chloride, bicarbonate, phosphate and organic acids generally in concentrations between 2� 10 mol and
–3
150 � 10 mol. A range of organic molecules such as proteins, enzymes and lipoproteins is also present, but their
concentrations may vary to a great extent. Earlier studies assumed that organic molecules did not exert a
significant influence on the degradation of metallic implants, but newer investigations indicate that implant
— protein interactions should be taken into account. Depending on a particular product or application, altering the
pH of the testing environment may also need to be considered.
In such biological environments, metallic materials may undergo a certain degradation and the different
degradation products may interact with the biological system in different ways. Therefore, the identification and
quantification of these degradation products is an important step in evaluating the biological performance of
medical devices.
vi © ISO 2000 – All rights reserved
---------------------- Page: 12 ----------------------
SIST EN ISO 10993-15:2009
INTERNATIONAL STANDARD ISO 10993-15:2000(E)
Biological evaluation of medical devices —
Part 15:
Identification and quantification of degradation products from
metals and alloys
1 Scope
This part of ISO 10993 provides guidance on general requirements for the design of tests for identifying and
quantifying degradation products from finished metallic medical devices or corresponding material samples finished
as ready for clinical use. It is applicable only to those degradation products generated by chemical alteration of the
finished metallic device in an in vitro accelerated degradation test. Because of the accelerated nature of these
tests, the test results may not reflect the implant or material behavior in the body. The described chemical
methodologies are a means to generate degradation products for further assessments.
This part of ISO 10993 is not applicable to degradation products induced by applied mechanical stress.
NOTE Mechanically induced degradation, such as wear, may be covered in the appropriate product-specific standard.
Where product-group standards provide applicable product-specific methodologies for the identification and quantification of
degradation products, those standards should be considered.
Because of the wide range of metallic materials used in medical devices, no specific analytical techniques are
–6
identified for quantifying the degradation products. The identification of
...
SLOVENSKI STANDARD
kSIST FprEN ISO 10993-15:2009
%LRORãNRRYUHGQRWHQMHPHGLFLQVNLKSULSRPRþNRYGHO ,GHQWLILNDFLMDLQ
XJRWDYOMDQMHNROLþLQHUD]JUDGQLKSURGXNWRYL]NRYLQLQ]OLWLQ ,62
Biological evaluation of medical devices - Part 15: Identification and quantification of
degradation products from metals and alloys (ISO 10993-15:2000)
Biologische Beurteilung von Medizinprodukten - Teil 15: Qualitativer und quantitativer
Nachweis von Abbauprodukten aus Metallen und Legierungen (ISO 10993-15:2000)
Evaluation biologique des dispositifs médicaux - Partie 15: Identification et quantification
des produits de dégradation issus des métaux et alliages (ISO 10993-15:2000)
Ta slovenski standard je istoveten z: FprEN ISO 10993-15
ICS:
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
kSIST FprEN ISO 10993-15:2009 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
---------------------- Page: 1 ----------------------
kSIST FprEN ISO 10993-15:2009
---------------------- Page: 2 ----------------------
kSIST FprEN ISO 10993-15:2009
EUROPEAN STANDARD
FINAL DRAFT
FprEN ISO 10993-15
NORME EUROPÉENNE
EUROPÄISCHE NORM
January 2009
ICS 11.100.20 Will supersede EN ISO 10993-15:2000
English Version
Biological evaluation of medical devices - Part 15: Identification
and quantification of degradation products from metals and
alloys (ISO 10993-15:2000)
Evaluation biologique des dispositifs médicaux - Partie 15: Biologische Beurteilung von Medizinprodukten - Teil 15:
Identification et quantification des produits de dégradation Qualitativer und quantitativer Nachweis von
issus des métaux et alliages (ISO 10993-15:2000) Abbauprodukten aus Metallen und Legierungen (ISO
10993-15:2000)
This draft European Standard is submitted to CEN members for unique acceptance procedure. It has been drawn up by the Technical
Committee CEN/TC 206.
If this draft becomes a European Standard, 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.
This draft European Standard was established by CEN 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.
Warning : This document is not a European Standard. It is distributed for review and comments. It is subject to change without notice and
shall not be referred to as a European Standard.
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. FprEN ISO 10993-15:2009: E
worldwide for CEN national Members.
---------------------- Page: 3 ----------------------
kSIST FprEN ISO 10993-15:2009
FprEN ISO 10993-15:2009 (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 .4
2
---------------------- Page: 4 ----------------------
kSIST FprEN ISO 10993-15:2009
FprEN ISO 10993-15:2009 (E)
Foreword
The text of ISO 10993-15:2000 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
FprEN ISO 10993-15:2009 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 10993-15:2000.
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 Directive 93/42/EEC on
Medical Devices.
For relationship with the EU Directive, see informative Annex ZA, which is an integral part of this document.
Endorsement notice
The text of ISO 10993-15:2000 has been approved by CEN as a FprEN ISO 10993-15:2009 without any
modification.
3
---------------------- Page: 5 ----------------------
kSIST FprEN ISO 10993-15:2009
FprEN ISO 10993-15:2009 (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, 6, 7, 8, 9
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
---------------------- Page: 6 ----------------------
kSIST FprEN ISO 10993-15:2009
INTERNATIONAL ISO
STANDARD 10993-15
First edition
2000-12-01
Corrected and reprinted
2001-04-01
Biological evaluation of medical devices —
Part 15:
Identification and quantification of
degradation products from metals and
alloys
Évaluation biologique des dispositifs médicaux —
Partie 15: Identification et quantification des produits de dégradation issus
des métaux et alliages
Reference number
ISO 10993-15:2000(E)
©
ISO 2000
---------------------- Page: 7 ----------------------
kSIST FprEN ISO 10993-15:2009
ISO 10993-15:2000(E)
PDF disclaimer
This PDF file may contain embedded typefaces. In accordance with Adobe's licensing policy, this file may be printed or viewed but shall not
be edited unless the typefaces which are embedded are licensed to and installed on the computer performing the editing. In downloading this
file, parties accept therein the responsibility of not infringing Adobe's licensing policy. The ISO Central Secretariat accepts no liability in this
area.
Adobe is a trademark of Adobe Systems Incorporated.
Details of the software products used to create this PDF file can be found in the General Info relative to the file; the PDF-creation parameters
were optimized for printing. Every care has been taken to ensure that the file is suitable for use by ISO member bodies. In the unlikely event
that a problem relating to it is found, please inform the Central Secretariat at the address given below.
© ISO 2000
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 either ISO at the address below or ISO's member body
in the country of the requester.
ISO copyright office
Case postale 56 � CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail copyright@iso.ch
Web www.iso.ch
Printed in Switzerland
ii © ISO 2000 – All rights reserved
---------------------- Page: 8 ----------------------
kSIST FprEN ISO 10993-15:2009
ISO 10993-15:2000(E)
Contents Page
Foreword.iv
Introduction.vi
1 Scope .1
2 Normative references .1
3 Terms and definitions .2
4 Degradation test methods .2
4.1 General.2
4.2 Prerequisites .3
5 Reagent and sample preparation.3
5.1 Sample documentation .3
5.2 Test solution (electrolyte) .3
5.3 Preparation of test samples.3
6 Electrochemical tests.4
6.1 Apparatus .4
6.2 Sample preparation .4
6.3 Test conditions .5
6.4 Potentiodynamic measurements .5
6.5 Potentiostatic measurements.5
7 Immersion test .5
7.1 Apparatus .5
7.2 Sample preparation .7
7.3 Immersion test procedure.7
8 Analysis .8
9 Test report .8
Annex A (informative) Schematic diagram of the electrochemical measuring circuit.9
Annex B (informative) Schematic drawing of an electrolytic cell .10
Annex C (informative) Examples of alternative electrolytes for the electrochemical tests.11
Bibliography.12
© ISO 2000 – All rights reserved iii
---------------------- Page: 9 ----------------------
kSIST FprEN ISO 10993-15:2009
ISO 10993-15:2000(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.
Attention is drawn to the possibility that some of the elements of this part of ISO 10993 may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights.
International Standard ISO 10993-15 was prepared by Technical Committee ISO/TC 194, Biological evaluation of
medical devices.
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 8: Selection and qualification of reference materials for biological tests
� Part 9: Framework for identification and quantification of potential degradation products
� Part 10: Tests for irritation and delayed-type hypersensitiviy
� Part 11: Tests for systemic toxicity
� Part 12: Sample preparation and reference materials
� Part 13: Identification and quantification of degradation products from polymeric medical devices
� 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
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kSIST FprEN ISO 10993-15:2009
ISO 10993-15:2000(E)
� Part 17: Establishment of allowable limits for leachable substances using health-based risk assessment
� Part 18: Chemical characterization of materials
Future parts will deal with other relevant aspects of biological testing.
Annexes A, B and C of this part of ISO 10993 are for information only.
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kSIST FprEN ISO 10993-15:2009
ISO 10993-15:2000(E)
Introduction
One of the potential health hazards resulting from medical devices may be due to the interactions of their
electrochemically-induced degradation products with the biological system. Therefore, the evaluation of potential
degradation products from metallic materials by methods suitable for testing the electrochemical behavior of these
materials is a necessary step in the biological performance testing of materials.
The body environment typically contains cations of sodium, potassium, calcium and magnesium and anions of
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chloride, bicarbonate, phosphate and organic acids generally in concentrations between 2� 10 mol and
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150 � 10 mol. A range of organic molecules such as proteins, enzymes and lipoproteins is also present, but their
concentrations may vary to a great extent. Earlier studies assumed that organic molecules did not exert a
significant influence on the degradation of metallic implants, but newer investigations indicate that implant
— protein interactions should be taken into account. Depending on a particular product or application, altering the
pH of the testing environment may also need to be considered.
In such biological environments, metallic materials may undergo a certain degradation and the different
degradation products may interact with the biological system in different ways. Therefore, the identification and
quantification of these degradation products is an important step in evaluating the biological performance of
medical devices.
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kSIST FprEN ISO 10993-15:2009
INTERNATIONAL STANDARD ISO 10993-15:2000(E)
Biological evaluation of medical devices —
Part 15:
Identification and quantification of degradation products from
metals and alloys
1 Scope
This part of ISO 10993 provides guidance on general requirements for the design of tests for identifying and
quantifying degradation products from finished metallic medical devices or corresponding material samples finished
as ready for clinical use. It is applicable only to those degradation products generated by chemical alteration of the
finished metallic device in an in vitro accelerated degradation test. Because of the accelerated nature of these
tests, the test results may not reflect the implant or material behavior in the body. The described chemical
methodologies are a means to generate degradation products for further assessments.
This part of ISO 10993 is not applicable to degradation products induced by applied mechanical stress.
NOTE Mechanically induced degradation, such as wear, may be covered in the appropriate product-specific standard.
Where product-group standards provide applicable product-specific methodologies for the identification and quantification of
degradation products, those standards should be considered.
Because of the wide range of metallic materials used in medical devices, no specific analytical techniques are
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identified for quantifying the degradation products. The identification of trace elements (< 10 ) contained in the
specific metal or alloy is not addressed in this part of ISO 10993, nor are specific requirements for acceptable
levels of degradation products provided in this part of ISO 10993.
This part of ISO 10993 does not address the biological activity of the degradation products; see instead the
applicable
...
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