SIST EN ISO 10993-13:2000

SLOVENSKI STANDARD
SIST EN ISO 10993-13:2000
01-januar-2000
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Biological evaluation of medical devices - Part 13: Identification and quantification of
degradation products from polymeric medical devices (ISO 10993-13:1998)
Biologische Beurteilung von Medizinprodukten - Teil 13: Qualitativer und quantitativer
Nachweis von Abbauprodukten in Medizinprodukten aus Polymeren (ISO 10993-
13:1998)
Evaluation biologique des dispositifs médicaux - Partie 13: Identification et quantification
de produits de dégradation de dispositifs médicaux a base de polymeres (ISO 10993-
13:1998)
Ta slovenski standard je istoveten z: EN ISO 10993-13:1998
ICS:
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
SIST EN ISO 10993-13:2000 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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INTERNATIONAL ISO
STANDARD 10993-13
First edition
1998-11-15
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
A
Reference number
ISO 10993-13:1998(E)

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ISO 10993-13:1998(E)
Contents Page
1 Scope . 1
2 Normative references . 1
3 Definitions . 2
4 Degradation test methods . 2
4.1 General procedures. 2
4.2 Accelerated degradation test . 5
4.3 Real-time degradation test. 5
5 Test procedures. 6
5.1 Initial material characterization . 7
5.2 Accelerated degradation test . 7
5.3 Real-time degradation test.8
6 Test report .9
Annex A  Analytical methods .10
©  ISO 1998
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 iso@iso.ch
Printed in Switzerland
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©
ISO ISO 10993-13:1998(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.
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 10993-13 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 cytotoxicity: in vitro methods
— 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
polymeric medical devices
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©
ISO 10993-13:1998(E) ISO
— 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
Annex A of this part of ISO 10993 is for information only.
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©
ISO ISO 10993-13:1998(E)
Introduction
This part of ISO 10993 was developed from ISO/TR 10993-9. Degradation
products covered by this standard are formed primarily by chemical bond
scission due to hydrolytic and/or oxidative processes in an aqueous
environment. It is recognized 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 may contain residuals and
leachables such as monomers, oligomers, solvents, catalysts, additives,
fillers and processing aids. These components which, if present, may
interfere with the identification and quantification of the degradation
products, need to be considered and accounted for. It should be
recognized that residual monomers may generate the same degradation
products as the polymer itself.
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 14538 and, if appropriate, for toxicokinetic studies
in accordance with ISO 10993-16.
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INTERNATIONAL STANDARD  © ISO ISO 10993-13:1998(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 guidance on general requirements for the design of tests 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. For materials which 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 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.
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 and ISO 14538.
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 standards contain provisions which, through reference in this text, constitute provisions of this part of
ISO 10993. At the time of publication, the editions indicated were valid. All standards are subject to revision, and
parties to agreements based on this part of ISO 10993 are encouraged to investigate the possibility of applying the
most recent editions of the standards indicated below. Members of IEC and ISO maintain registers of currently valid
International Standards.
ISO 3696:1987, Water for analytical laboratory use — Specification and test methods.
ISO 10993-1:1997, Biological evaluation of medical devices — Part 1: Evaluation and testing.
1)
ISO 10993-9:— , Biological evaluation of medical devices — Part 9: Framework for identification and quantification
of potential degradation products.
ISO 10993-12:1996, Biological evaluation of medical devices — Part 12: Sample preparation and reference
materials.

1)
To be published.
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© ISO
ISO 10993-13:1998(E)
ISO 10993-16:1997, Biological evaluation of medical devices — Part 16: Toxicokinetic study design for degradation
products and leachables.
ISO 13781:1997, Poly(L-lactide) resins and fabricated forms for surgical implants — In vitro degradation testing.
1)
ISO 14538:— Biological evaluation of medical devices — Establishment of permissible limits for sterilization and
process residues using health-based risk assessment.
3 Definitions
For the purposes of this part of ISO 10993, the definitions given in ISO 10993-1, ISO 10993-9, ISO 13781 and the
following definitions apply.
3.1  residual monomer
unreacted chemical compound(s) used to build the polymeric chains and 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 may have a neutral, acidic or alkaline pH value and may contain additional chemical compounds or ions.
3.5  oxidative degradation
scission of chemical bonds in a polymer by the attack of oxidizing agent(s)
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 may provide sufficient information for risk analysis. Where this information is insufficient or absent, real
time testing shall be performed. The sequence of steps which shall be followed is described in detail in this part of
ISO 10993.
NOTE The accelerated degradation test may 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.
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© ISO
ISO 10993-13:1998(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 of this part of ISO 10993 presents a list of analytical methods and their application range for the
characterization of polymeric materials.
4.1.4 Reagents and apparatus
4.1.4.1 Test solutions
All test solution(s) used shall be described and justified in the test report.
4.1.4.1.1 Reagents 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, e.g. in accordance with ISO 13781.
4.1.4.1.2 Reagents 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+
Fenton´s reagent [mixture of dilute hydrogen peroxide solution and iron(II) salts, e.g. 100 μmol Fe and 1 mmol
b)
H O ].
2 2
These oxidative solutions may 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.
4.1.4.1.3 Other test solutions
Other test solutions for a specific polymer or a specific application site 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 may be necessary to maintain a sterile environment for the duration of the real-
time degradation test.
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.
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 accuracy of the balance for resorbable polymers shall
be 0,1 %, and for stable polymers 0,01 %,of the total sample mass.
The precision and standard deviation of the method of the determination of mass loss shall be stated in the test
report.
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© ISO
ISO 10993-13:1998(E)
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 (< 500 Pa) in the drying apparatus is appropriate.
The apparatus shall be desc
...