SIST EN ISO 10993-13:2010

Biological evaluation of medical devices - Part 13: Identification and quantification of degradation products from polymeric medical devices (ISO 10993-13:2010)

This part of ISO 10993 provides general requirements for the design of tests in a simulated environment for identifying and quantifying degradation products from finished polymeric medical devices ready for clinical use. This part of ISO 10993 describes two test methods to generate degradation products, an accelerated degradation test as a screening method and a real-time degradation test in a simulated environment. For materials that are intended to polymerize in situ, the set or cured polymer is used for testing. The data generated are used in the biological evaluation of the polymer. This part of ISO 10993 considers only nonresorbable polymers. Similar but appropriately modified procedures may be applicable for resorbable polymers. This part of ISO 10993 considers only those degradation products generated by a chemical alteration of the finished polymeric device. It is not applicable to degradation of the device induced during its intended use by mechanical stress, wear or electromagnetic radiation or biological factors such as enzymes, other proteins and cellular activity.

Biologische Beurteilung von Medizinprodukten - Teil 13: Qualitativer und quantitativer Nachweis von Abbauprodukten in Medizinprodukten aus Kunststoff (ISO 10993-13:2010)

Dieser Teil von ISO 10993 legt allgemeine Anforderungen an den Entwurf und an die Auslegung von Prüfungen in einer simulierten Umgebung, zur Identifizierung und Quantifizierung von Abbauprodukten aus fertig bearbeiteten Medizinprodukten aus Kunststoff, so wie sie in der Klinik zur Anwendung kommen, fest.
Dieser Teil von ISO 10993 beschreibt zwei Prüfmethoden zur Erzeugung von Abbauprodukten, eine beschleunigte Abbauprüfung als Screeningmethode und eine Echtzeitabbauprüfung in einer simulierten Umgebung. Für Materialien, die dafür gedacht sind, in situ zu polymerisieren, wird für die Prüfung der abgebundene oder ausgehärtete Kunststoff verwendet. Die erhaltenen Daten dienen zur biologischen Beurteilung der Kunststoffe. Das vorliegende Dokument betrachtet lediglich nicht-resorbierbare Polymere. Ähnliche, jedoch entsprechend modifizierte Verfahren können für resorbierbare Polymere anwendbar sein.
Dieser Teil von ISO 10993 beschreibt nur die Abbauprodukte, die durch eine chemische Veränderung des fertigen Kunststoffproduktes erzeugt werden. Er ist nicht anwendbar auf jenen Abbau von Medizinprodukten, der während der vorgesehenen Anwendung durch mechanische Belastungen, durch Abrieb, durch elektromagnetische Strahlung oder durch biologische Mediatoren wie Enzyme, andere Proteine und zelluläre Aktivität entsteht.
ANMERKUNG 1   Abbauprodukte im Sinne dieser Norm bilden sich bevorzugt durch Spaltung chemischer Bindungen durch hydrolytische und/oder oxidative Prozesse in einer wässrigen Umgebung wie im menschlichen Körper. Es ist jedoch bekannt, dass zusätzliche biologische Faktoren wie Enzyme, andere Proteine und zelluläre Aktivität die Geschwindigkeit und die Art des Abbaus verändern können.
ANMERKUNG 2   Ein informativer Text zur umgebungsbedingten Spannungsrissbildung (ESC) von Polymeren ist als mögliche Hilfe für die Konzipierung von Degradationsstudien beigefügt (siehe Annex B).

Évaluation biologique des dispositifs médicaux - Partie 13: Identification et quantification de produits de dégradation de dispositifs médicaux à base de polymères (ISO 10993-13:2010)

L'ISO 10993-13:2010 fournit des exigences générales pour la conception des essais dans un environnement simulé permettant d'identifier et de quantifier les produits de dégradation de dispositifs médicaux à base de polymères destinés à un usage médical.
L'ISO 10993-13:2010 décrit deux méthodes d'essai permettant de générer des produits de dégradation, un essai de dégradation accélérée utilisée comme méthode à effet éliminatoire et un essai de dégradation en temps réel dans un environnement simulé. Pour les matériaux destinés à polymériser in situ, le polymère durci ou cuit doit être utilisé pour les essais. Les données obtenues doivent être utilisées lors de l'évaluation biologique du polymère. L'ISO 10993-13:2010 ne prend en considération que les polymères non résorbables. Des modes opératoires similaires, mais auxquels ont été apportées les modifications appropriées, peuvent s'appliquer aux polymères résorbables.
L'ISO 10993-13:2010 ne traite que des produits de dégradation résultant d'une altération chimique du dispositif médical à base de polymères dans son état final. Elle ne s'applique pas à la dégradation consécutive à une contrainte mécanique, à l'usure, à des rayonnements électromagnétiques ou à des facteurs biologiques tels que les enzymes, d'autres protéines et l'activité cellulaire, au cours de la durée d'utilisation prévue.

Biološko ovrednotenje medicinskih pripomočkov - 13. del: Prepoznavanje in ugotavljanje količine razgradnih produktov polimerov, iz katerih so izdelani medicinski pripomočki (ISO 10993-13:2010)

Ta del ISO 10993 podaja splošne zahteve za načrtovanje preskusov v simuliranem okolju za prepoznavanje in ugotavljanje količine razgradnih produktov iz dokončanih medicinskih naprav iz polimerov, pripravljenih za klinično uporabo. Ta del ISO 10993 opisuje dve preskusni metodi za pridobivanje razgradnih produktov, pospešeni preskus razgradnje kot metodo presajanja ter preskus razgradnje v realnem času v simuliranem okolju. Pri materialih, ki so namenjeni za in situ polimerizacijo, se za preskušanje uporabi ulit ali vulkaniziran polimer. Pridobljeni podatki se uporabijo za biološko vrednotenje polimera. Ta del ISO 10993 obravnava le neabsorbtivne polimere. Podobni, vendar primerno spremenjeni postopki, lahko veljajo za absorptivne polimere. Ta del ISO 10993 obravnava le tiste postopke razgradnje, ki jih generira kemična sprememba dokončanih naprav iz polimerov. Ne velja za razgradnjo naprave, ki je inducirana med njeno predvideno uporabo z mehanskim udarcem, obrabo ali elektromagnetnim sevanjem oziroma z biološkimi dejavniki, kot so encimi,  drugi proteini in celična dejavnost.

General Information

• Status: Published
• Publication Date: 07-Oct-2010
• ICS: 11.100.20 - Biological evaluation of medical devices
• Technical Committee: VAZ - Healthcare
• Current Stage: 6060 - National Implementation/Publication (Adopted Project)
• Start Date: 25-Aug-2010
• Due Date: 30-Oct-2010
• Completion Date: 08-Oct-2010
• Directive: 90/385/EEC - Council Directive 90/385/EEC of 20 June 1990 on the approximation of the laws of the Member States relating to active implantable medical devices
• Directive: 93/42/EEC - Council Directive 93/42/EEC of 14 June 1993 concerning medical devices
• 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: EN ISO 10993-13:2010 - Biological evaluation of medical devices - Part 13: Identification and quantification of degradation products from polymeric medical devices (ISO 10993-13:2010)

Relations

• Replaces: SIST EN ISO 10993-13:2009 - Biological evaluation of medical devices - Part 13: Identification and quantification of degradation products from polymeric medical devices (ISO 10993-13:1998)
• Effective Date: 01-Dec-2010
• Replaces: SIST EN ISO 10993-13:2009 - Biological evaluation of medical devices - Part 13: Identification and quantification of degradation products from polymeric medical devices (ISO 10993-13:1998)
• Effective Date: 08-Jun-2022

Standards Content (Sample)

SLOVENSKI STANDARD
SIST EN ISO 10993-13:2010
01-december-2010
1DGRPHãþD
SIST EN ISO 10993-13:2009
%LRORãNRRYUHGQRWHQMHPHGLFLQVNLKSULSRPRþNRYGHO3UHSR]QDYDQMHLQ
XJRWDYOMDQMHNROLþLQHUD]JUDGQLKSURGXNWRYSROLPHURYL]NDWHULKVRL]GHODQL
PHGLFLQVNLSULSRPRþNL,62
Biological evaluation of medical devices - Part 13: Identification and quantification of
degradation products from polymeric medical devices (ISO 10993-13:2010)
Biologische Beurteilung von Medizinprodukten - Teil 13: Qualitativer und quantitativer
Nachweis von Abbauprodukten in Medizinprodukten aus Kunststoff (ISO 10993-13:2010)
Évaluation biologique des dispositifs médicaux - Partie 13: Identification et quantification
de produits de dégradation de dispositifs médicaux à base de polymères (ISO 10993-
13:2010)
Ta slovenski standard je istoveten z: EN ISO 10993-13:2010
ICS:
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
SIST EN ISO 10993-13:2010 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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SIST EN ISO 10993-13:2010

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SIST EN ISO 10993-13:2010


EUROPEAN STANDARD
EN ISO 10993-13

NORME EUROPÉENNE

EUROPÄISCHE NORM
June 2010
ICS 11.100.20 Supersedes EN ISO 10993-13:2009
English Version
Biological evaluation of medical devices - Part 13: Identification
and quantification of degradation products from polymeric
medical devices (ISO 10993-13:2010)
Évaluation biologique des dispositifs médicaux - Partie 13: Biologische Beurteilung von Medizinprodukten - Teil 13:
Identification et quantification de produits de dégradation Qualitativer und quantitativer Nachweis von
de dispositifs médicaux à base de polymères (ISO 10993- Abbauprodukten in Medizinprodukten aus Polymeren (ISO
13:2010) 10993-13:2010)
This European Standard was approved by CEN on 5 June 2010.

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, Croatia, 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
© 2010 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 10993-13:2010: E
worldwide for CEN national Members.

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SIST EN ISO 10993-13:2010
EN ISO 10993-13:2010 (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
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 10993-13:2010
EN ISO 10993-13:2010 (E)
Foreword
This document (EN ISO 10993-13:2010) has been prepared by Technical Committee ISO/TC 194 "Biological
evaluation of medical devices" in collaboration with 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 2010, and conflicting national standards shall be withdrawn
at the latest by December 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 10993-13:2009.
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.
For relationship with EU Directives, see informative Annex ZA and ZB, which are integral parts 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, Croatia, 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 10993-13:2010 has been approved by CEN as a EN ISO 10993-13:2010 without any
modification.
3

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SIST EN ISO 10993-13:2010
EN ISO 10993-13:2010 (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 European Standard is cited in the Official Journal of the European Union under that Directive and
has been implemented as a national standard in at least one Member State, compliance with the clauses of
this European Standard given in Table ZA.1 confers, within the limits of the scope of this Intenational
Standard, a presumption of conformity with the corresponding Essential Requirements of that Directive and
associated EFTA regulations.
Table ZA.1 — Correspondence between this European Standard and Directive 93/42/EEC on Medical
devices
Clause(s)/subclause(s) of Essential Requirements (ERs) of Directive Qualifying remarks/notes
this European Standard 93/42/EEC on Medical devices
These relevant Essential
4, 5 and 6 7.1 and 7.5
Requirements are only partly
addressed in this standard.

General note: Presumption of conformity depends on also complying with all relevant clauses/subclauses of
ISO 10993-1.

WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this European Standard.
4

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SIST EN ISO 10993-13:2010
EN ISO 10993-13:2010 (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 European Standard is cited in the Official Journal of the European Union under that Directive and
has been implemented as a national standard in at least one Member State, compliance with the clauses of
this European Standard given in Table ZB.1 confers, within the limits of the scope of this European Standard,
a presumption of conformity with the corresponding Essential Requirements of that Directive and associated
EFTA regulations.
Table ZB.1 — Correspondence between this European Standard and Directive 90/385/EEC on Active
Implantable Medical Devices

Essential Requirements (ERs) of
Clause(s)/subclause(s) of this Qualifying remarks/notes
Directive 90/385/EEC on Active
European Standard
Implantable Medical Devices
4, 5 and 6 9 (first and second indents only) The first and second indents of
this relevant Essential
Requirement are only partly
addressed in this standard.

General note: Presumption of conformity depends on also complying with all relevant clauses/subclauses of
ISO 10993-1.

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

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SIST EN ISO 10993-13:2010

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SIST EN ISO 10993-13:2010

INTERNATIONAL ISO
STANDARD 10993-13
Second edition
2010-06-15


Biological evaluation of medical
devices —
Part 13:
Identification and quantification of
degradation products from polymeric
medical devices
Évaluation biologique des dispositifs médicaux —
Partie 13: Identification et quantification de produits de dégradation de
dispositifs médicaux à base de polymères





Reference number
ISO 10993-13:2010(E)
©
ISO 2010

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SIST EN ISO 10993-13:2010
ISO 10993-13:2010(E)
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ii © ISO 2010 – All rights reserved

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SIST EN ISO 10993-13:2010
ISO 10993-13:2010(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 procedures.2
4.2 Accelerated degradation test .5
4.3 Real-time degradation test in a simulated environment .6
5 Test procedures.6
5.1 General .6
5.2 Initial material characterization.6
5.3 Accelerated degradation test .6
5.4 Real-time degradation test in a simulated environment .9
6 Test report.10
Annex A (informative) Analytical methods.11
Annex B (informative) Environmental stress cracking (ESC) of polymers.12
Bibliography.14

© ISO 2010 – All rights reserved iii

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SIST EN ISO 10993-13:2010
ISO 10993-13:2010(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 2.
The main task of technical committees is to prepare International Standards. 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 document may be the subject of patent
rights. ISO shall not be held responsible for identifying any or all such patent rights.
ISO 10993-13 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices.
This second edition cancels and replaces the first edition (ISO 10993-13:1998), 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 within a risk management process
⎯ 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 identification and quantification of potential degradation products
⎯ Part 10: Tests for irritation and skin sensitization
⎯ 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
iv © ISO 2010 – All rights reserved

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SIST EN ISO 10993-13:2010
ISO 10993-13:2010(E)
⎯ Part 16: Toxicokinetic study design for degradation products and leachables
⎯ Part 17: Establishment of allowable limits for leachable substances
⎯ Part 18: Chemical characterization of materials
⎯ Part 19: Physico-chemical, morphological and topographical characterization of materials [Technical
specification]
⎯ Part 20: Principles and methods for immunotoxicology testing of medical devices [Technical specification]
© ISO 2010 – All rights reserved v

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SIST EN ISO 10993-13:2010
ISO 10993-13:2010(E)
Introduction
Degradation products covered by this part of ISO 10993 are formed primarily by chemical bond scission due
to hydrolytic and/or oxidative processes in an aqueous environment such as the human body. It is recognised
that additional biological factors, such as enzymes, other proteins and cellular activity, can alter the rate and
nature of degradation.
It should be kept in mind that a polymeric device can contain residuals and leachables such as monomers,
oligomers, solvents, catalysts, additives, fillers and processing aids. These components which, if present, can
interfere with the identification and quantification of the degradation products need to be considered and
accounted for. It should be recognised that residual monomers can generate the same degradation products
as the polymer itself. If the reader is solely interested in using the results from a degradation test as input to
further biological evaluation tests, the reader might not be interested in distinguishing between a leachable
and a degradation product. If this is the case, then the care taken to separate the leachable from the
degradation product may not be needed.
Because of the generalized nature of this part of ISO 10993, product standards, when available, that address
degradation product formation under more relevant conditions of use, may be considered as an alternative.
This part of ISO 10993 is suitable for screening new polymeric materials and/or modified polymeric materials
with unknown degradation behaviour in body contact. This part of ISO 10993 does not reproduce degradation
in vivo. The user of this part of ISO 10993 can consider running additional degradation tests addressing
in vivo degradation issues.
Long-term implants might not degrade within the time frame of the tests shown in this part of ISO 10993. The
intention of this part of ISO 10993 is to help determine the biological hazards from potential degradation
products from polymer components of medical devices. As noted above, those products might come from a
variety of degradation mechanisms. This part of ISO 10993 is not intended to be a complete analysis of the
degradation of the medical device and the impact on its performance. The interested user is referred to the
relevant product standards.
The identified and quantified degradation products form the basis for biological evaluation in accordance with
ISO 10993-1, for risk assessment in accordance with ISO 10993-17 and, if appropriate, for toxicokinetic
studies in accordance with ISO 10993-16.
vi © ISO 2010 – All rights reserved

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SIST EN ISO 10993-13:2010
INTERNATIONAL STANDARD ISO 10993-13:2010(E)

Biological evaluation of medical devices —
Part 13:
Identification and quantification of degradation products from
polymeric medical devices
1 Scope
This part of ISO 10993 provides general requirements for the design of tests in a simulated environment for
identifying and quantifying degradation products from finished polymeric medical devices ready for clinical use.
This part of ISO 10993 describes two test methods to generate degradation products, an accelerated
degradation test as a screening method and a real-time degradation test in a simulated environment. For
materials that are intended to polymerize in situ, the set or cured polymer is used for testing. The data
generated are used in the biological evaluation of the polymer. This part of ISO 10993 considers only non-
resorbable polymers. Similar but appropriately modified procedures may be applicable for resorbable
polymers.
This part of ISO 10993 considers only those degradation products generated by a chemical alteration of the
finished polymeric device. It is not applicable to degradation of the device induced during its intended use by
mechanical stress, wear or electromagnetic radiation or biological factors such as enzymes, other proteins
and cellular activity.
NOTE An informative text discussing environmental stress cracking (ESC) of polymers is included as a potential aid
to the design of degradation studies (see Annex B).
The biological activity of the debris and soluble degradation products is not addressed in this part of
ISO 10993, but should be evaluated according to the principles of ISO 10993-1, ISO 10993-16 and
ISO 10993-17.
Because of the wide range of polymeric materials used in medical devices, no specific analytical techniques
are identified or given preference. No specific requirements for acceptable levels of degradation products are
provided in this part of ISO 10993.
2 Normative references
The following referenced documents are indispensable for the application 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 3696, Water for analytical laboratory use — Specification and test methods
ISO 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
ISO 10993-9, Biological evaluation of medical devices — Part 9: Framework for identification and
quantification of potential degradation products
© ISO 2010 – All rights reserved 1

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SIST EN ISO 10993-13:2010
ISO 10993-13:2010(E)
ISO 10993-12, Biological evaluation of medical devices — Part 12: Sample preparation and reference materials
ISO 10993-17, Biological evaluation of medical devices — Part 17: Establishment of allowable limits for
leachable substances
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
3.1
residual monomer
unreacted chemical compound(s) used to build the polymeric chains, which is still present in the final
polymeric material
3.2
degradation product
chemical compound derived from the breakdown of the polymeric material, including any compound produced
by consecutive chemical reactions
3.3
polymeric material
materials consisting of long-chain and/or crosslinked molecules composed of units called monomers
3.4
hydrolytic degradation
scission of chemical bonds in a polymer by the attack of water
NOTE The water can have a neutral, acidic or alkaline pH value and can contain additional chemical compounds or ions.
3.5
oxidative degradation
scission of chemical bonds in a polymer by the attack of one or more oxidizing agents
3.6
debris
particulate material produced by the degradation of a polymeric material
4 Degradation test methods
4.1 General procedures
4.1.1 Test design
In accordance with ISO 10993-9, degradation tests shall be used to generate, identify and/or quantify
degradation products. If degradation is observed in an accelerated test, identification and quantification of the
degradation products can provide sufficient information for risk analysis. If identification and quantification of
degradation products from the accelerated test do not provide sufficient information for the risk analysis,
real-time testing shall be performed. The sequence of steps that shall be followed is described in detail in this
part of ISO 10993.
NOTE The accelerated degradation test can be used as a screening test. If no degradation is observed in the
accelerated test, no real-time degradation test should be necessary.
4.1.2 Sample preparation
When not specifically addressed by the selected method(s), the general aspects of sample preparation shall
be in accordance with ISO 10993-12.
2 © ISO 2010 – All rights reserved

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SIST EN ISO 10993-13:2010
ISO 10993-13:2010(E)
4.1.3 Initial material characterization
The analytical methods used for the initial material characterization shall be appropriate for the polymeric
material under investigation. The analytical techniques used shall be reported and justified.
Annex A presents a list of analytical methods and their application range for the characterization of polymeric
materials.
4.1.4 Test solutions and apparatus
4.1.4.1 Test solutions
4.1.4.1.1 General
All test solution(s) used shall be described and justified in the test report.
The test solution shall be selected to be as similar as possible to the intended environment in which the
polymeric medical device is going to be used.
If the service environment cannot be simulated, test solutions given in 4.1.4.1.2 and 4.1.4.1.3 can be used as
a first screening for degradation. These test solutions can be more challenging or less challenging to the
polymeric material with respect to the intended degradation mechanisms than the in vivo environment.
Other test solutions for a specific polymer or a specific service environment may be chosen.
NOTE If a biological assay of the debris or the degradation solution is to be made, then the use of antibacterial or
antifungal additives will interfere with these assays and it might be necessary to maintain a sterile environment for the
duration of the real-time degradation test.
4.1.4.1.2 Test solutions for hydrolytic degradation
For hydrolytic degradation, the following solutions are suggested:
a) water for analytical laboratory use, grade 2, in accordance with ISO 3696;
b) buffer.
NOTE See ISO 13781 for examples of buffers used in hydrolytic degradation studies.
4.1.4.1.3 Test solutions for oxidative degradation
For oxidative degradation, the following solutions are suggested:
a) water and hydrogen peroxide, e.g. 3 % hydrogen peroxide solution, Pharmacopoeia grade;
2+
b) Fenton's reagent [mixture of dilute hydrogen peroxide solution and iron(II) salts, e.g. 100 µmol Fe and
1 mmol H O ].
2 2
These oxidative solutions might not be stable at elevated temperatures or for a prolonged time. Therefore, the
oxidative capacity shall be maintained in an appropriate range.
This stability range shall be specified, justified and reported.
4.1.4.2 Container
Depending on the test solution, chemical grade glassware, polytetrafluoroethylene or polypropylene
containers in an enclosed system shall be used. Controls shall be used in order to assess contaminants from
the container. Evidence shall be provided that containers do not interfere with the analysis.
© ISO 2010 – All rights reserved 3

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SIST EN ISO 10993-13:2010
ISO 10993-13:2010(E)
4.1.4.3 Balance
The balance used to determine mass loss shall be capable of weighing the initial sample mass with the
precision required. For materials designed to be resorbed, a precision of 1 % is appropriate, for materials
designed to resist degradation, a precision of at least 0,1 % shall be used. The precision of the balance for the
final sample mass in the case of resorbable polymers shall be 0,1 %, and in the case of stable polymers
0,01 %, of the total sample mass.
The precision and standard deviation of the method used for determining mass loss shall be stated in the test
report.
4.1.4.4 Drying apparatus
Any apparatus capable of drying the test samples to constant mass without contamination or loss of volatile
degradation products shall be used.
The apparatus shall be described and defined in the test report.
4.1.4.5 Vacuum source
Any apparatus capable of producing a sufficient vacuum (< 0,5 kPa) in the drying apparatus is appropriate.
The apparatus shall be described and defined in the test report.
4.1.4.6 Separation apparatus
Any apparatus capable of separating the debris produced during the degradation study may be used. This can
involve an inert filter, a temperature-controlled centrifuge or a combination thereof.
The apparatus shall be described and defined in the test report.
4.1.5 Number of test samples
At least three test samples shall be used for each test period. These should be the finished product itself or
representative samples thereof. A separate container shall be used for each sample. One blank shall be used
for each test period.
If a valid statistical analysis is required, more samples at each test period should be used, as appropriate.
4.1.6 Shape and size of test samples
The size and the shape of the specimen are critical for the generation of relevant amounts of degradation
products. If a
...