SIST EN ISO 10993-15:2001

SLOVENSKI STANDARD
SIST EN ISO 10993-15:2001
01-november-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 10993-15:2000
ICS:
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
SIST EN ISO 10993-15:2001 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

---------------------- Page: 1 ----------------------

SIST EN ISO 10993-15:2001

---------------------- Page: 2 ----------------------

SIST EN ISO 10993-15:2001
EUROPEAN STANDARD
EN ISO 10993-15
NORME EUROPÉENNE
EUROPÄISCHE NORM
December 2000
ICS 11.100
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 European Standard was approved by CEN on 1 December 2000.
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 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 Management Centre has the same status as the official
versions.
CEN members are the national standards bodies of Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece,
Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: rue de Stassart, 36  B-1050 Brussels
© 2000 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 10993-15:2000 E
worldwide for CEN national Members.

---------------------- Page: 3 ----------------------

SIST EN ISO 10993-15:2001
Page 2
EN ISO 10993-15:2000
Foreword
Corrected 2001-03-08
The text of the International Standard ISO 10993-15:2000 has been prepared by Technical
Committee ISO/TC 194 "Biological evaluation of medical devices" in collaboration with
Technical Committee CEN/TC 206 "Biocompatibility of medical and dental materials and
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 June 2001, and conflicting national
standards shall be withdrawn at the latest by June 2001.
This European Standard 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(s).
According to the CEN/CENELEC Internal Regulations, the national standards organizations of
the following countries are bound to implement this European Standard: Austria, Belgium,
Czech Republic, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy,
Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United
Kingdom.
Endorsement notice
The text of the International Standard ISO 10993-15:2000 was approved by CEN as a
European Standard without any modification.
NOTE: Normative references to International Standards are listed in annex ZA (normative).

---------------------- Page: 4 ----------------------

SIST EN ISO 10993-15:2001
Page 3
EN ISO 10993-15:2000
Annex ZA (normative)
Normative references to international publications
with their relevant European publications
This European Standard incorporates by dated or undated reference, provisions from other
publications. These normative references are cited at the appropriate places in the text and the
publications are listed hereafter. For dated references, subsequent amendments to or revisions
of any of these publications apply to this European Standard only when incorporated in it by
amendment or revision. For undated references the latest edition of the publication referred to
applies (including amendments).
NOTE Where an International Publication has been modified by common modifications,
indicated by (mod.), the relevant EN/HD applies.
Publication Year Title EN Year
ISO 3696 1987 Water for analytical laboratory use — EN ISO 3696 1995
Specification and test methods
ISO 8044 1999 Corrosion of metals and alloys — Basic EN ISO 8044 1999
terms and definitions
ISO 10993-1 1997 Biological evaluation of medical EN ISO 10993-1 1997
devices — Part 1: Evaluation and testing
ISO 10993-9 1999 Biological evaluation of medical EN ISO 10993-9 1999
devices — Part 9: Framework for
identification and quantification of
potential degradation products
ISO 10993-12 1996 Biological evaluation of medical EN ISO 10993-12 1996
devices — Part 12: Sample preparation
and reference materials
ISO 10993-13 1998 Biological evaluation of medical EN ISO 10993-13 1998
devices — Part 13: Identification and
quantification of degradation products
from polymeric medical devices
ISO 10993-16 1997 Biological evaluation of medical EN ISO 10993-16 1997
devices — Part 16: Toxicokinetic study
design for degradation products and
leachables

---------------------- Page: 5 ----------------------

SIST EN ISO 10993-15:2001

---------------------- Page: 6 ----------------------

SIST EN ISO 10993-15:2001
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 10993-15:2001
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 10993-15:2001
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 10993-15:2001
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 10993-15:2001
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

---------------------- Page: 11 ----------------------

SIST EN ISO 10993-15:2001
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 10993-15:2001
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 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
...