SIST EN ISO 10993-9:2022
(Main)Biological evaluation of medical devices - Part 9: Framework for identification and quantification of potential degradation products (ISO 10993-9:2019)
Biological evaluation of medical devices - Part 9: Framework for identification and quantification of potential degradation products (ISO 10993-9:2019)
This document provides general principles for the systematic evaluation of the potential and observed
degradation of medical devices through the design and performance of in vitro degradation studies.
Information obtained from these studies can be used in the biological evaluation described in the
ISO 10993 series.
This document is applicable to both materials designed to degrade in the body as well as materials that
are not intended to degrade.
This document is not applicable to:
a) the evaluation of degradation which occurs by purely mechanical processes; methodologies for the
production of this type of degradation product are described in specific product standards, where
available;
NOTE Purely mechanical degradation causes mostly particulate matter. Although this is excluded from
the scope of this document, such degradation products can evoke a biological response and can undergo
biological evaluation as described in other parts of ISO 10993.
b) leachable components which are not degradation products;
c) medical devices or components that do not contact the patient's body directly or indirectly
Biologische Beurteilung von Medizinprodukten - Teil 9: Rahmen zur Identifizierung und Quantifizierung von möglichen Abbauprodukten (ISO 10993-9:2019)
Dieses Dokument beschreibt allgemeine Prinzipien zur systematischen Beurteilung von möglichem und beobachtetem Abbau bei Medizinprodukten durch Planung und Durchführung von In vitro Abbaustudien. Informationen, die aus diesen Studien resultieren, können für die in der Normenreihe ISO 10993 beschriebene biologische Beurteilung verwendet werden.
Dieses Dokument gilt sowohl für Materialien, die dafür vorgesehen sind, vom Körper abgebaut zu werden, als auch für solche, bei denen das nicht vorgesehen ist.
Dieses Dokument gilt nicht für:
a) die Beurteilung des Abbaus durch rein mechanische Prozesse. Methoden zur Generierung dieser Art von Abbauprodukten sind, falls vorhanden, in den spezifischen Produktnormen beschrieben;
ANMERKUNG Rein mechanischer Abbau verursacht meist Partikel. Obwohl diese aus dem Anwendungsbereich dieses Dokuments ausgeschlossen sind, können solche Abbauprodukte eine biologische Reaktion hervorrufen und können daher einer biologischen Beurteilung, wie in anderen Teilen der ISO 10993 beschrieben, unterzogen werden.
b) herauslösbare Komponenten, die keine Abbauprodukte sind;
c) Medizinprodukte oder deren Komponenten, die weder direkt noch indirekt mit dem Körper des Patienten in Berührung kommen.
Évaluation biologique des dispositifs médicaux - Partie 9: Cadre pour l'identification et la quantification des produits potentiels de dégradation (ISO 10993-9:2019)
Le présent document donne les principes généraux pour l'évaluation systématique de la dégradation potentielle et observée des dispositifs médicaux, à travers la conception et l'exécution des études de dégradation in vitro. Les informations obtenues dans le cadre de ces études peuvent servir aux évaluations biologiques décrites dans la série de normes ISO 10993.
Le présent document s'applique aux matériaux conçus pour se dégrader dans le corps, ainsi qu'aux matériaux qui ne sont pas conçus pour se dégrader.
Le présent document ne s'applique pas:
a) à l'évaluation de la dégradation qui se produit uniquement suite à des processus mécaniques; les méthodologies de génération de ce type de produit de dégradation sont décrites, le cas échéant, dans les normes des produits considérés;
NOTE La dégradation purement mécanique donne principalement de la matière sous forme de particules. Bien qu'ils n'entrent pas dans le domaine d'application du présent document, de tels produits de dégradation peuvent entraîner une réponse biologique et peuvent être soumis à une évaluation biologique telle que celle décrite dans les autres parties de l' ISO 10993.
b) aux composants relargables qui ne sont pas des produits de dégradation;
c) aux dispositifs médicaux ou composants qui ne sont pas directement ou indirectement en contact avec le corps du patient.
Biološko ovrednotenje medicinskih pripomočkov - 9. del: Okvirni sistem za prepoznavanje in ugotavljanje količine morebitnih razgradnih produktov (ISO 10993-9:2019)
Ta dokument podaja splošna načela za sistematično ovrednotenje morebitne in opažene razgradnje medicinskih pripomočkov z načrtovanjem in izvedbo študij razgradnje in vitro. Informacije, pridobljene s temi študijami, je mogoče uporabiti pri biološkem ovrednotenju, ki je opisano v skupini standardov ISO 10993. Ta dokument se uporablja za materiale, namenjene razgradnji v telesu, in materiale, ki niso namenjeni razgradnji. Ta dokument se ne uporablja za: a) ovrednotenje razgradnje, ki jo povzročajo izključno mehanski procesi; metodologije za proizvodnjo takšnega razgradnega produkta so opisane v standardih za posamezni izdelek, če so na voljo. OPOMBA: Pri izključno mehanski razgradnji nastanejo večinoma trdni delci. Čeprav to ne spada na področje uporabe tega dokumenta, lahko takšni razgradni produkti izzovejo biološki odziv in so lahko predmet biološkega ovrednotenja, kot je opisano v drugih delih standarda ISO 10993; b) izlužene komponente, ki niso produkti razgradnje; c) medicinske pripomočke ali komponente, ki so v neposrednem ali posrednem stiku z bolnikovim telesom.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 10993-9:2022
01-januar-2022
Nadomešča:
SIST EN ISO 10993-9:2010
Biološko ovrednotenje medicinskih pripomočkov - 9. del: Okvirni sistem za
prepoznavanje in ugotavljanje količine morebitnih razgradnih produktov (ISO
10993-9:2019)
Biological evaluation of medical devices - Part 9: Framework for identification and
quantification of potential degradation products (ISO 10993-9:2019)
Biologische Beurteilung von Medizinprodukten - Teil 9: Rahmen zur Identifizierung und
Quantifizierung von möglichen Abbauprodukten (ISO 10993-9:2019)
Évaluation biologique des dispositifs médicaux - Partie 9: Cadre pour l'identification et la
quantification des produits potentiels de dégradation (ISO 10993-9:2019)
Ta slovenski standard je istoveten z: EN ISO 10993-9:2021
ICS:
11.100.20 Biološko ovrednotenje Biological evaluation of
medicinskih pripomočkov medical devices
SIST EN ISO 10993-9:2022 en,fr,de
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 10993-9:2022
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SIST EN ISO 10993-9:2022
EN ISO 10993-9
EUROPEAN STANDARD
NORME EUROPÉENNE
September 2021
EUROPÄISCHE NORM
ICS 11.100.20 Supersedes EN ISO 10993-9:2009
English Version
Biological evaluation of medical devices - Part 9:
Framework for identification and quantification of
potential degradation products (ISO 10993-9:2019)
Évaluation biologique des dispositifs médicaux - Partie Biologische Beurteilung von Medizinprodukten - Teil 9:
9: Cadre pour l'identification et la quantification des Rahmen zur Identifizierung und Quantifizierung von
produits potentiels de dégradation (ISO 10993- möglichen Abbauprodukten (ISO 10993-9:2019)
9:2019)
This European Standard was approved by CEN on 26 May 2021.
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-CENELEC 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-CENELEC 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, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2021 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 10993-9:2021 E
worldwide for CEN national Members.
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SIST EN ISO 10993-9:2022
EN ISO 10993-9:2021 (E)
Contents Page
European foreword . 3
Annex ZA (informative) Relationship between this European Standard and the general
health and safety requirements of Regulation (EU) 2017/745 on medical devices
aimed to be covered . 5
2
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SIST EN ISO 10993-9:2022
EN ISO 10993-9:2021 (E)
European foreword
This document (EN ISO 10993-9:2021) has been prepared by Technical Committee ISO/TC 194
"Biological and clinical evaluation of medical devices" in collaboration with Technical Committee
CEN/TC 206 “Biological and clinical evaluation of medical devices” the secretariat of which is held by
DIN.
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 March 2022, and conflicting national standards shall
be withdrawn at the latest by March 2022.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 10993-9:2009.
This document has been prepared under a Standardization Request given to CEN by the European
Commission and the European Free Trade Association, and supports essential requirements of EU
Directive(s) / Regulation(s).
For the relationship with EU Directive(s) / Regulation(s), see informative Annex ZA, which is an integral
part of this document.
Any feedback and questions on this document should be directed to the users’ national standards
body/national committee. A complete listing of these bodies can be found on the CEN websites.
The following referenced documents are indispensable for the application of this document. For
undated references, the latest edition of the referenced document (including any amendments) applies.
For dated references, only the edition cited applies. However, for any use of this document ‘within the
meaning of Annex ZA’, the user should always check that any referenced document has not been
superseded and that its relevant contents can still be considered the generally acknowledged state-of-
art.
When an IEC or ISO standard is referred to in the ISO standard text, this shall be understood as a
normative reference to the corresponding EN standard, if available, and otherwise to the dated version
of the ISO or IEC standard, as listed below.
NOTE The way in which these referenced documents are cited in normative requirements determines the
extent (in whole or in part) to which they apply.
3
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SIST EN ISO 10993-9:2022
EN ISO 10993-9:2021 (E)
Table — Correlations between undated normative references and dated EN and ISO standards
Normative references as Equivalent dated standard
listed in Clause 2 of the ISO
EN ISO or IEC
standard
b
ISO 10993-1 EN ISO 10993-1:2020 ISO 10993-1:2018
a
ISO 10993-2 EN ISO 10993-2:2020 ISO 10993-2: 2020
ISO 10993-13 EN ISO 10993-13:2010 ISO 10993-13:2010
ISO 10993-14 EN ISO 10993-14:2009 ISO 10993-14:2001
b
ISO 10993-15 EN ISO 10993-15:2020 ISO 10993-15:2019
a
Under preparation. Documents are at final stage and have to be submitted to ISO/CS for FDIS vote.
a
Under preparation at European level.
NOTE This part of EN ISO 10993 refers to ISO 10993-1 which itself refers to ISO 14971. In Europe, it should
be assumed that the reference to ISO 14971 is to EN ISO 14971:2020.
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, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the
United Kingdom.
Endorsement notice
The text of ISO 10993-9:2019 has been approved by CEN as EN ISO 10993-9:2021 without any
modification.
4
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SIST EN ISO 10993-9:2022
EN ISO 10993-9:2021 (E)
Annex ZA
(informative)
Relationship between this European Standard and the general health and
safety requirements of Regulation (EU) 2017/745 on medical devices aimed
to be covered
This European standard has been prepared under a Commission’s standardisation request to provide
one voluntary means of conforming to the General Safety and Performance Requirements of Regulation
(EU) 2017/745 of 5 April 2017 concerning medical devices [OJ L 117].
Once this standard is cited in the Official Journal of the European Union under that Regulation,
compliance with the normative clauses of this standard given in Table ZA.1 confers, within the limits of
the scope of this standard, a presumption of conformity with the corresponding General Safety and
Performance Requirements of that Regulation, and associated EFTA regulations.
NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk
management process needs to be in compliance with Regulation (EU) 2017/745. This means that risks have to be
‘reduced as far as possible’, ‘reduced to the lowest possible level’, ‘reduced as far as possible and appropriate’,
‘removed or reduced as far as possible’, ‘eliminated or reduced as far as possible’, ’removed or minimized as far as
possible’, or ‘minimized’, according to the wording of the corresponding General Safety and Performance
Requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with General Safety
and Performance Requirements 1, 2, 3, 4, 5, 8, 9, 10, 11, 14, 16, 17, 18, 19, 20, 21 and 22 of the Regulation.
NOTE 3 This Annex ZA is based on normative references according to the table of references in the European
Foreword, replacing the references in the core text.
NOTE 4 When a General Safety and Performance Requirement does not appear in Table ZA.1, it means that it is
not addressed by this European Standard.
Table ZA.1 — Correspondence between this European Standard and Annex I of Regulation (EU)
2017/745
General health and safety Clause(s)/sub-clause(s) of Remarks/Notes
Requirements of Regulation this EN
(EU) 2017/745
10.1 a), b), c) and h) 4 and Annex A 10.1 a), b), c) and h) only partly
covered by ISO 10993-9, since
the standard does not provide
requirements on design and
manufacture.
However, this part of ISO 10993
provides considerations on how
to plan a degradation study in
order to obtain quantitative
degradation data as a basis for
the safety evaluation of a
medical device.
Therefore, this standard
5
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SIST EN ISO 10993-9:2022
EN ISO 10993-9:2021 (E)
provides a means to evaluate
degradation risks associated
with the materials which are
used.
More product group specific
information can be found in
ISO 10993-13 (polymers),
ISO 10993-14 (ceramics) and
ISO 10993-15 (metals and
alloys)
These tests are not intended to
evaluate or determine the
performance of the test sample
in terms of mechanical or
functional loading.
For 10.1 a), flammability is not
covered.
10.4.1 (first paragraph) 4 and Annex A 10.4.1 is only partly covered by
this document. However, this
part of ISO 10993 specifies the
general principles that govern
the design, conduct and
interpretation of studies to
identify and quantify
degradation products arising
from materials intended for use
in medical devices in order to
obtain quantitative degradation
data as a basis for the safety
evaluation of a medical device.
Therefore, this standard
provides a means to investigate
the risks posed by degradation
products that may be released
from the medical device.
This document does not apply
to particles, wear debris or
processing residues
General Note: Presumption of conformity depends on also complying with the relevant parts of the ISO 10993-
series.
WARNING 1 — Presumption of conformity stays valid only as long as a reference to this European
Standard is maintained in the list published in the Official Journal of the European Union. Users of this
standard should consult frequently the latest list published in the Official Journal of the European
Union.
WARNING 2 — Other Union legislation may be applicable to the product(s) falling within the scope of
this standard.
6
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SIST EN ISO 10993-9:2022
INTERNATIONAL ISO
STANDARD 10993-9
Third edition
2019-11
Biological evaluation of medical
devices —
Part 9:
Framework for identification
and quantification of potential
degradation products
Évaluation biologique des dispositifs médicaux —
Partie 9: Cadre pour l'identification et la quantification des produits
potentiels de dégradation
Reference number
ISO 10993-9:2019(E)
©
ISO 2019
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SIST EN ISO 10993-9:2022
ISO 10993-9:2019(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2019
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting
on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address
below or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Fax: +41 22 749 09 47
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2019 – All rights reserved
---------------------- Page: 10 ----------------------
SIST EN ISO 10993-9:2022
ISO 10993-9:2019(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Principles for design of degradation studies . 2
4.1 General . 2
4.2 Preliminary considerations . 3
4.3 Study design . 3
4.4 Characterization of degradation products from medical devices . 4
5 Study report . 4
Annex A (normative) Consideration of the need for degradation studies .6
Annex B (informative) Degradation study considerations . 8
Bibliography .11
© ISO 2019 – All rights reserved iii
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SIST EN ISO 10993-9:2022
ISO 10993-9:2019(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.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).
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. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www .iso .org/ patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation of the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to the
World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see www .iso .org/
iso/ foreword .html.
This document was prepared by Technical Committee ISO/TC 194, Biological and clinical evaluation of
medical devices.
This third edition cancels and replaces the second edition (ISO 10993-9:2009), which has been
technically revised.
The main changes compared to the previous edition are as follows:
a) biodegradation changed to degradation;
b) information on test methods amended to consider nanomaterials and relevant material specific
standards.
A list of all parts in the ISO 10993 series can be found on the ISO website.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www .iso .org/ members .html.
iv © ISO 2019 – All rights reserved
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SIST EN ISO 10993-9:2022
ISO 10993-9:2019(E)
Introduction
This document is intended to present the general principles on which the specific material investigations
to identify and quantify degradation products described in ISO 10993-13 (polymers), ISO 10993-14
(ceramics) and ISO 10993-15 (metals and alloys) are based.
Information obtained from these studies is intended to be used in the biological evaluations described
in the remaining parts of ISO 10993.
The materials used to construct medical devices can form degradation products when exposed to the
biological environment, and in the body these products might behave differently to the bulk material.
Mechanical
...
SLOVENSKI STANDARD
oSIST prEN 10993-9:2018
01-junij-2018
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Biological evaluation of medical devices - Part 9: Framework for identification and
quantification of potential degradation products (ISO/DIS 10993-9:2018)
Biologische Beurteilung von Medizinprodukten - Teil 9: Rahmen zur Identifizierung und
Quantifizierung von möglichen Abbauprodukten (ISO/DIS 10993-9:2018)
Évaluation biologique des dispositifs médicaux - Partie 9: Cadre pour l'identification et la
quantification des produits potentiels de dégradation (ISO/DIS 10993-9:2018)
Ta slovenski standard je istoveten z: prEN ISO 10993-9
ICS:
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
oSIST prEN 10993-9:2018 en,fr,de
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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oSIST prEN 10993-9:2018
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oSIST prEN 10993-9:2018
DRAFT INTERNATIONAL STANDARD
ISO/DIS 10993-9
ISO/TC 194 Secretariat: DIN
Voting begins on: Voting terminates on:
2018-04-24 2018-07-17
Biological evaluation of medical devices —
Part 9:
Framework for identification and quantification of
potential degradation products
Évaluation biologique des dispositifs médicaux —
Partie 9: Cadre pour l'identification et la quantification des produits potentiels de dégradation
ICS: 11.100.20
THIS DOCUMENT IS A DRAFT CIRCULATED
This document is circulated as received from the committee secretariat.
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
IN ADDITION TO THEIR EVALUATION AS
ISO/CEN PARALLEL PROCESSING
BEING ACCEPTABLE FOR INDUSTRIAL,
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
STANDARDS MAY ON OCCASION HAVE TO
BE CONSIDERED IN THE LIGHT OF THEIR
POTENTIAL TO BECOME STANDARDS TO
WHICH REFERENCE MAY BE MADE IN
Reference number
NATIONAL REGULATIONS.
ISO/DIS 10993-9:2018(E)
RECIPIENTS OF THIS DRAFT ARE INVITED
TO SUBMIT, WITH THEIR COMMENTS,
NOTIFICATION OF ANY RELEVANT PATENT
RIGHTS OF WHICH THEY ARE AWARE AND TO
©
PROVIDE SUPPORTING DOCUMENTATION. ISO 2018
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oSIST prEN 10993-9:2018
ISO/DIS 10993-9:2018(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2018
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting
on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address
below or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Fax: +41 22 749 09 47
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2018 – All rights reserved
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oSIST prEN 10993-9:2018
ISO/DIS 10993-9:2018(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Principles for design of degradation studies . 2
4.1 General . 2
4.2 Preliminary considerations . 3
4.3 Study design . 3
4.4 Characterization of degradation products from medical devices . 4
5 Study report . 4
Annex A (normative) Consideration of the need for degradation studies .5
Annex B (informative) Degradation study considerations . 7
Annex ZA (informative) Relationship between this European Standard and the essential
requirements of Directive 93/42/EEC [OJ L 169] aimed to be covered .10
Annex ZB (informative) Relationship between this European Standard and the essential
requirements of Directive 90/385/EEC [OJ L 189] aimed to be covered .11
Annex ZC (informative) Relationship between this European Standard and the general
health and safety requirements of Regulation (EU) 2017/745 on medical devices
aimed to be covered .13
Bibliography .15
© ISO 2018 – All rights reserved iii
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oSIST prEN 10993-9:2018
ISO/DIS 10993-9:2018(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.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).
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. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www .iso .org/ patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity assessment,
as well as information about ISO's adherence to the World Trade Organization (WTO) principles in the
Technical Barriers to Trade (TBT) see the following URL: www .iso .org/ iso/ foreword .html.
This document was prepared by Technical Committee ISO/TC 194, Biological and clinical evaluation of
medical devices.
This third edition cancels and replaces the second edition (ISO 10993-9:2009), which has been
technically revised.
The main changes compared to the previous edition are as follows:
a) biodegradation changed to degradation;
b) information on test methods amended to consider nanomaterials and relevant material specific
standards;
A list of all parts in the ISO 10993- series can be found on the ISO website.
iv © ISO 2018 – All rights reserved
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Introduction
This document is intended to present the general principles on which the specific material investigations
to identify and quantify degradation products described in ISO 10993-13 (polymers), ISO 10993-14
(ceramics) and ISO 10993-15 (metals and alloys) are based.
Information obtained from these studies is intended to be used in the biological evaluations described
in the remaining parts of ISO 10993.
The materials used to construct medical devices can form degradation products when exposed to the
biological environment, and in the body these products might behave differently to the bulk material.
Mechanical wear, which is not in scope of this standard, causes mostly particulate debris, whereas the
release of substances from surfaces due to leaching, chemical breakdown of structures or corrosion
can lead to free ions or to different kinds of reaction products in the form of organic or inorganic
compounds.
The degradation products can be either reactive or stable and without biochemical reaction with their
environment. Accumulations of substantial quantities of stable degradation products can, however,
have physical effects on the surrounding tissues. Degradation products might remain at the location
of their generation or might be transported within the biological environment by various mechanisms.
The level of biological tolerability of degradation products depends on their nature and concentration,
and should be primarily assessed through clinical experience and focused studies. For theoretically
possible, new and/or unknown degradation products, relevant testing is necessary. For well-described
and clinically accepted degradation products, further investigation need not be necessary.
Note that the safety and efficacy of a medical device can be compromised as a result of any unintended
or premature degradation, which should be considered in the risk management of the device.
This document can be applied to the degradation of materials used in any kind of product that falls
within the definition of “medical device” in ISO 10993-1, even if such products are subject to different
regulations from those applying to medical devices, e.g. the scaffold in a tissue engineered medical
product, or a carrier matrix to deliver drugs or biologics.
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DRAFT INTERNATIONAL STANDARD ISO/DIS 10993-9:2018(E)
Biological evaluation of medical devices —
Part 9:
Framework for identification and quantification of
potential degradation products
1 Scope
This document provides general principles for the systematic evaluation of the potential and observed
degradation of medical devices through the design and performance of in vitro degradation studies.
Information obtained from these studies can be used in the biological evaluation described in the
ISO 10993- series.
This document considers both materials designed to degrade in the body as well as materials that are
not intended to degrade.
This document is not applicable to:
a) evaluation of degradation which occurs by purely mechanical processes; methodologies for the
production of this type of degradation product are described in specific product standards, where
available;
NOTE Purely mechanical degradation causes mostly particulate matter. Although this is excluded from
the scope of this document, such degradation products can evoke a biological response and thus need to
undergo biological evaluation as described in other parts of ISO 10993.
b) leachable components which are not degradation products;
c) medical devices or components that do not contact the patient's body directly or indirectly.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements 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 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
ISO 10993-2, Biological evaluation of medical devices — Part 2: Animal welfare requirements
ISO 10993-13, Biological evaluation of medical devices — Part 13: Identification and quantification of
degradation products from polymeric medical devices
ISO 10993-14, Biological evaluation of medical devices — Part 14: Identification and quantification of
degradation products from ceramics
ISO 10993-15, Biological evaluation of medical devices — Part 15: Identification and quantification of
degradation products from metals and alloys
ISO 13781, Implants for surgery — Homopolymers, copolymers and blends on poly(lactide) — In vitro
degradation testing
ISO/TR 10993-22, Biological evaluation of medical devices — Part 22: Guidance on nanomaterials
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3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 10993-1 and the following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
IEC Electropedia: available at http:// www .electropedia .org/
ISO Online browsing platform: available at https:// www .iso .org/ obp
3.1
degradation
decomposition of a material
3.2
absorb
action of a non-endogenous (foreign) material or substance passing through or being assimilated by
cells and/or tissue over time
3.3
leachable
substances that can be released from a medical device or material during clinical use
3.4
corrosion
attack on metallic materials by chemical or electrochemical reactions
Note 1 to entry: The term is sometimes used in a general sense for the deterioration of other materials but is in
this part of ISO 10993 reserved for metallic materials.
3.5
substance
single chemical element or compound, or a complex structure of compounds
3.6
device component
one of the different parts of which a device is composed
3.7
degradation product
particle or chemical compound that is derived from the chemical breakdown of the original material
3.8
service environment
anatomical location for the intended use of the device including surrounding fluids, tissues and
biomolecules
4 Principles for design of degradation studies
4.1 General
The approach to the assessment of degradation varies with the nature of the material under investigation,
the medical device and the anatomical location of the specific device. The in vitro degradation models
chosen for evaluation shall be representative of these factors. The studies to be conducted do not
require a biological environment, but one that simulates the conditions of the intended clinical use.
Experience has shown that in some degradation processes, in vitro models do not reflect all aspects of
the service environment, e.g. mechanical processes can influence degradation, and should be taken into
account when defining the model service environment.
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Experience has also shown that material property changes during degradation can result in different
biological responses. The user is urged to be aware of those property changes and apply the relevant
material specific standards (e.g. crystallization of polymers).
Materials-specific or product-specific degradation standards that address identification and
quantification of degradation products should be considered in the design of degradation studies.
ISO 10993-13 (for polymers), ISO 10993-14 (for ceramics) or ISO 10993-15 (for metals and alloys) shall
apply if no suitable material-specific standard exists. Devices composed of two or more material types
should consider all relevant degradation standards.
ISO 10993-13, ISO 10993-14 and ISO 10993-15 consider only those degradation products generated by a
chemical alteration of the finished device. They are not applicable to degradation of the device induced
during its intended use by mechanical stress, wear or electromagnetic radiation. For such degradation
other methods should be considered.
4.2 Preliminary considerations
Careful consideration of the potential for intended or unintended degradation of a material is essential
to the evaluation of the biological safety of a device. Part of this consideration is an assessment of the
chemical characteristics and known degradation mechanisms, followed by an assessment of the need
for, and design of, experimental degradation studies.
It is neither necessary nor practical to conduct degradation studies for all medical devices. Consideration
of the need for degradation studies is provided in Annex A. The assessment of the need for experimental
degradation studies shall include a review of the literature and/or documented clinical experience.
Guidance on proper reviewing of the literature can be found in ISO 10993-1. Such an assessment can
potentially result in the conclusion that no further testing is needed.
Guidance on the biological evaluation of leachables including degradation products is given in
ISO 10993-1, ISO 10993-16 and ISO 10993-17. See ISO 10993-12 for guidance on the extraction of
leachables from medical devices and ISO 10993-18 for guidance on the chemical characterization
of materials and their leachables used in medical devices. See ISO/TS 10993-19 for guidance on the
physico-chemical, morphological and topographical characterization of materials. Consideration of
these standards prior to conducting degradation studies can prove helpful in distinguishing degradation
products from other leachables.
NOTE Despite the difference between degradation products and other leachables, it might be possible to
combine a study on degradation products with a study on other leachable components. Distinguishing between
degradation products and other types of leachables need not be necessary for further biological evaluation
studies. However, when a reduction of the level of leachable components is deemed necessary as a risk control
measure, this information is important. Additionally, some degradation products can not leach from the device,
but still impact the properties of the device.
4.3 Study design
A degradation study plan complete with the purpose of the study shall be designed and documented
to address the issues identified in 4.1. The approved study plan shall define the analytical methods by
which the following characteristics of degradation products are to be investigated:
a) chemical properties;
b) physicochemical properties;
c) physical morphology (as applicable).
The approved study plan shall also describe the methods used to generate degradation products. The
methods should be optimized for detection of degradable substances and justified.
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The approved study plan for multi-component device
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