SIST EN ISO 13408-2:2018
(Main)Aseptic processing of health care products - Part 2: Sterilizing filtration (ISO 13408-2:2018)
Aseptic processing of health care products - Part 2: Sterilizing filtration (ISO 13408-2:2018)
This document specifies requirements for sterilizing filtration as part of aseptic processing of health
care products conducted in accordance with ISO 13408-1. It also offers guidance to filter users
concerning general requirements for set-up, validation and routine operation of a sterilizing filtration
process.
This document is not applicable to removal of viruses.
Sterilizing filtration is not applicable to fluids that intentionally contain particles larger than the pore
size of the filter (e.g. bacterial whole-cell vaccines).
This document is not applicable to high efficiency particulate air (HEPA) filters.
This document does not specify requirements for the development, validation and routine control of a
process for removing the causative agents of spongiform encephalopathies such as scrapie, bovine
spongiform encephalopathy and Creutzfeldt-Jakob disease. Specific recommendations have been produced
in particular countries for the processing of materials potentially contaminated with these agents.
Aseptische Herstellung von Produkten für die Gesundheitsfürsorge - Teil 2: Sterilfiltration (ISO 13408-2:2018)
1.1 Einschlüsse
Der vorliegende Teil von ISO 13408 legt die Anforderung an die in Übereinstimmung mit ISO 13408 1 durchgeführte Sterilfiltration als Teil der aseptischen Herstellung von Produkten für die Gesundheits-fürsorge fest. Er stellt auch einen Leitfaden für die Filteranwender hinsichtlich der allgemeinen Anforderungen an Einrichtung, Validierung und routinemäßigen Betrieb eines Prozesses der Sterilfiltration zur Verfügung.
1.2 Ausschlüsse
1.2.1 Der vorliegende Teil von ISO 13408 gilt nicht für das Entfernen von Viren.
1.2.2 Sterilfiltration ist nicht bei Fluiden anwendbar, die absichtlich Partikel enthalten, deren Größe die Porengröße des Filters überschreitet (z. B. bakterielle Ganzzellimpfstoffe).
1.2.3 Der vorliegende Teil von ISO 13408 gilt nicht für Schwebstofffilter (eng: High Efficiency Particulate Air; HEPA).
1.2.4 Diese internationale Norm legt keine Anforderungen für die Entwicklung, Validierung und Routinekontrolle eines Prozesses zur Entfernung der Erreger spongiformer Encephalopathien wie Scrapie, boviner spongiformer Encephalopathie und Creutzfeldt Jakob Krankheit fest. In bestimmten Ländern wurden spezifische Empfehlungen für die Verarbeitung von Materialien entwickelt, die möglicherweise mit diesen Erregern kontaminiert sind.
Traitement aseptique des produits de santé - Partie 2: Filtration stérilisante (ISO 13408-2:2018)
ISO 13408-2:2018 spécifie les exigences de filtration stérilisante dans le cadre du traitement aseptique des produits de santé, mené conformément à ISO 13408‑1. Il propose également aux utilisateurs de filtres des recommandations concernant les exigences générales pour la configuration, la validation et les opérations de routine d'un processus de filtration stérilisante.
ISO 13408-2:2018 ne concerne pas l'élimination des virus.
La filtration stérilisante ne s'applique pas aux fluides contenant volontairement des particules de taille supérieure à la dimension des pores du filtre (par exemple: vaccins à cellules bactériennes entières).
ISO 13408-2:2018 ne s'applique pas aux filtres HEPA (High Efficiency Particulate Air).
ISO 13408-2:2018 ne spécifie pas d'exigences relatives à l'élaboration, à la validation et au contrôle de routine d'un processus d'élimination des agents de prolifération de l'encéphalopathie spongiforme, telle que la tremblante du mouton, l'encéphalopathie spongiforme bovine et la maladie de Creutzfeldt-Jakob. Des recommandations spécifiques ont été rédigées dans des pays déterminés pour le traitement des matériaux potentiellement contaminés par ces agents.
Aseptična proizvodnja izdelkov za zdravstveno nego - 2. del: Sterilizacija s filtracijo (ISO 13408-2:2018)
Ta dokument določa zahteve za sterilizacijo s filtracijo v okviru aseptične proizvodnje izdelkov za zdravstveno nego, izvedene v skladu s standardom ISO 13408-1. Zagotavlja tudi smernice za uporabnike filtrov v zvezi s splošnimi zahtevami za pripravo, potrjevanje in redno izvajanje postopka sterilizacije s filtracijo.
Ta dokument se ne uporablja za odstranjevanje virusov.
Sterilizacija s filtracijo se ne uporablja za tekočine, ki namenoma vsebujejo delce, večje od velikosti por filtra (npr. bakterijska cepiva s celimi celicami).
Ta dokument se ne uporablja za visoko učinkovite zračne filtre drobnih delcev (HEPA).
Ta dokument ne določa zahtev za razvoj, validacijo in rutinsko kontrolo postopka za odstranjevanje povzročiteljev spongiformne encefalopatije, kot so praskavec, bovina spongiformna encefalopatija in Creutzfeldt-Jakobova bolezen. V posameznih državah so bila izdelana posebna priporočila za obdelavo materialov, potencialno okuženih s temi povzročitelji.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 13408-2:2018
01-julij-2018
1DGRPHãþD
SIST EN ISO 13408-2:2011
$VHSWLþQDSURL]YRGQMDL]GHONRY]D]GUDYVWYHQRQHJRGHO 6WHULOL]DFLMDV
ILOWUDFLMR ,62
Aseptic processing of health care products - Part 2: Sterilizing filtration (ISO 13408-
2:2018)
Aseptische Herstellung von Produkten für die Gesundheitsfürsorge - Teil 2: Sterilfiltration
(ISO 13408-2:2018)
Traitement aseptique des produits de santé - Partie 2: Filtration stérilisante (ISO 13408-
2:2018)
Ta slovenski standard je istoveten z: EN ISO 13408-2:2018
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
SIST EN ISO 13408-2:2018 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 13408-2:2018
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SIST EN ISO 13408-2:2018
EN ISO 13408-2
EUROPEAN STANDARD
NORME EUROPÉENNE
March 2018
EUROPÄISCHE NORM
ICS 11.080.01 Supersedes EN ISO 13408-2:2011
English Version
Aseptic processing of health care products - Part 2:
Sterilizing filtration (ISO 13408-2:2018)
Traitement aseptique des produits de santé - Partie 2: Aseptische Herstellung von Produkten für die
Filtration stérilisante (ISO 13408-2:2018) Gesundheitsfürsorge - Teil 2: Sterilfiltration (ISO
13408-2:2018)
This European Standard was approved by CEN on 2 January 2018.
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, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, 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
© 2018 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 13408-2:2018 E
worldwide for CEN national Members.
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SIST EN ISO 13408-2:2018
EN ISO 13408-2:2018 (E)
Contents Page
European foreword . 3
Endorsement notice . 4
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on active implantable medical devices
[OJ L 189] aimed to be covered . 5
Annex ZB (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices [OJ L 169] aimed to be
covered. 6
Annex ZC (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devices [OJ L
331] aimed to be covered . 7
2
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SIST EN ISO 13408-2:2018
EN ISO 13408-2:2018 (E)
European foreword
This document (EN ISO 13408-2:2018) has been prepared by Technical Committee ISO/TC 198
"Sterilization of health care products" in collaboration with Technical Committee CEN/TC 204
“Sterilization of medical devices” the secretariat of which is held by BSI.
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 September 2018, and conflicting national standards
shall be withdrawn at the latest by September 2018.
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 13408-2:2011.
This document has been prepared under a mandate given to CEN by the European Commission and the
European Free Trade Association, and supports essential requirements of EU Directive(s).
For relationship with EU Directive(s), see informative Annex ZA, B, and C, which are an integral part of
this document.
The following referenced documents are indispensable for the application of this document. For
undated references, the edition of the referenced document (including any amendments) listed below
applies. For dated references, only the edition cited applies. However, for any use of this standard
within the meaning of Annexes ZA, ZB or ZC, 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 should 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.
Table — Correlation between normative references and dated EN and ISO standards
Normative references as Equivalent dated standard
listed in Clause 2 of the ISO
EN ISO
standard
ISO 13408-1:2008 + Amd EN ISO 13408-1:2015 ISO 13408-1:2008 + Amd 1:2013
1:2013
ISO 13408-5 EN ISO 13408-5:2011 ISO 13408-5:2006
ISO 11135 EN ISO 11135:2014 ISO 11135:2014
ISO 11137-1 EN ISO 11137-1:2015 ISO 11137-1:2006 + Amd 1:2013
ISO/DIS 11139:2017 prEN ISO 11139:2017 ISO/DIS 11139:2017
3
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SIST EN ISO 13408-2:2018
EN ISO 13408-2:2018 (E)
Normative references as Equivalent dated standard
listed in Clause 2 of the ISO
EN ISO
standard
ISO 13485 EN ISO 13485:2016 + AC:2016 ISO 13485:2016
ISO 17665-1 EN ISO 17665-1:2006 ISO 17665-1:2006
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, Former Yugoslav Republic of Macedonia,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,
Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and the United Kingdom.
Endorsement notice
The text of ISO 13408-2:2018 has been approved by CEN as EN ISO 13408-2:2018 without any
modification.
4
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SIST EN ISO 13408-2:2018
EN ISO 13408-2:2018 (E)
Annex ZA
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on active implantable medical
devices [OJ L 189] aimed to be covered
This European standard has been prepared under a Commission’s standardisation request M/023 to
provide one voluntary means of conforming to essential requirements of 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 [OJ L 189].
Once this standard is cited in the Official Journal of the European Union under that Directive,
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 Essential Requirements
of that Directive 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 90/385/EEC, as amended by 2007/47/EC. This means that
risks have to be reduced ‘as far as possible’, ‘to a minimum’, ‘to the lowest possible level’, ‘minimized’ or ‘removed’,
according to the wording of the corresponding essential requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with essential
requirements 1, 4, 5, 8, 9 and 10 of the Directive.
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 an Essential 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 Directive
90/385/EEC [OJ L 189]
Essential
Requirements (ERs) of Clauses of this EN Qualifying remarks/Notes
Directive 90/385/EEC
7 4,5,6,7,8,9,10,11,12 Only a sterilization process using filtration as part
of an aseptic process is considered by this standard
and only in conjunction with EN ISO 13408-1.
This relevant Essential Requirement is only partly
addressed in this European Standard. Design and
packaging for maintenance of sterility during
transportation and storage are not covered. Aspects
of manufacture other than those related to
sterilization by filtration are not covered.
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 products falling within the scope of this
standard.
5
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SIST EN ISO 13408-2:2018
EN ISO 13408-2:2018 (E)
Annex ZB
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices [OJ L 169]
aimed to be covered
This European Standard has been prepared under a Commission's standardization request M/023 to
provide one voluntary means of conforming to essential requirements of Council Directive 93/42/EEC
of 14 June 1993 concerning medical devices [OJ L 169].
Once this standard is cited in the Official Journal of the European Union under that Directive,
compliance with the normative clauses of this standard given in Table ZB.1 confers, within the limits of
the scope of this standard, a presumption of conformity with the corresponding Essential Requirements
of that Directive and associated EFTA regulations.
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 93/42/EEC, as amended by 2007/47/EC. This means that
risks have to be reduced ‘as far as possible’, ‘to a minimum’, ‘to the lowest possible level’, ‘minimized’ or ‘removed’,
according to the wording of the corresponding essential requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with essential
requirements 1, 2, 5, 6, 7, 8, 9, 11 and 12 of the Directive.
NOTE 3 This Annex ZB 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 an Essential Requirement does not appear in Table ZB.1, it means that it is not addressed by this
European Standard.
Table ZB.1 — Correspondence between this European Standard and Annex I of Directive
93/42/EEC [OJ L 169]
Essential
Requirements (ERs) Clauses of
Qualifying remarks/Notes
of Directive this EN
93/42/EEC
8.3 4,5,6,7,8,9,10 Only a sterilization process using filtration as part of an aseptic
,11,12 process is considered by this standard and only in conjunction
with EN ISO 13408-1.
This relevant Essential Requirement is only partly addressed in
this European Standard. Design and packaging for maintenance
of sterility during transportation and storage are not covered.
Aspects of manufacture other than those related to sterilization
by filtration are not covered.
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 products falling within the scope of this
standard.
6
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SIST EN ISO 13408-2:2018
EN ISO 13408-2:2018 (E)
Annex ZC
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 98/79/EC on in vitro diagnostic medical
devices [OJ L 331] aimed to be covered
This European standard has been prepared under a Commission’s standardisation request, M/252,
concerning the development of European standards relating to in vitro diagnostic medical devices, to
provide one voluntary means of conforming to essential requirements of Directive 98/79/EC of the
European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices [OJ L
331].
Once this standard is cited in the Official Journal of the European Union under that Directive,
compliance with the normative clauses of this standard given in Table ZC.1 confers, within the limits of
the scope of this standard, a presumption of conformity with the corresponding Essential Requirements
of that Directive and associated EFTA regulations.
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 98/79/EC. This means that risks have to be reduced ‘as far
as possible’, ‘to a minimum’, ‘to the lowest possible level’, ‘minimized’ or ‘removed’, according to the wording of
the corresponding essential requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with essential
requirements Part A: 1, 2 and 5; Part B: 1.2, 2, 3, 5, 6, and 7 of the Directive.
NOTE 3 This Annex ZC 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 an Essential Requirement does not appear in Table ZC.1, it means that it is not addressed by this
European Standard.
Table ZC.1 — Correspondence between this European Standard and Annex I of Directive
98/79/EC [OJ L 331]
Essential Requirements (ERs) of Clauses of this
Qualifying remarks/Notes
Directive 98/79/EC EN
B.2.3 4,5,6,7,8,9,10,1 Only a sterilization process using filtration as part
1,12 of an aseptic process is considered by this standard
and only in conjunction with EN ISO 13408-1.
This relevant Essential Requirement is only partly
addressed in this European Standard. Design and
packaging for maintenance of sterility during
transportation and storage are not covered. Aspects
of manufacture other than those related to
sterilization by filtration are not covered.
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 products falling within the scope of this
standard.
7
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SIST EN ISO 13408-2:2018
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SIST EN ISO 13408-2:2018
INTERNATIONAL ISO
STANDARD 13408-2
Second edition
2018-01
Aseptic processing of health care
products —
Part 2:
Sterilizing filtration
Traitement aseptique des produits de santé —
Partie 2: Filtration stérilisante
Reference number
ISO 13408-2:2018(E)
©
ISO 2018
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SIST EN ISO 13408-2:2018
ISO 13408-2:2018(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
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copyright@iso.org
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Published in Switzerland
ii © ISO 2018 – All rights reserved
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SIST EN ISO 13408-2:2018
ISO 13408-2:2018(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Quality system elements . 3
4.1 General . 3
4.2 Management responsibility . 3
4.3 Procurement of filters . 3
5 Sterilizing filter characterization . 3
5.1 General . 3
5.2 Microbial removal effectiveness. 4
5.3 Material effects. 4
5.4 Environmental considerations . 5
6 Process and equipment characterization . 5
6.1 General . 5
6.2 Risk management . 5
6.3 Process characterization . 6
6.4 Equipment characterization . 6
7 Fluid definition . 7
7.1 General . 7
7.2 Microbiological quality . 8
8 Process definition . 8
8.1 General . 8
8.2 Filter definition and characterization . 9
8.2.1 General. 9
8.2.2 Compatibility between the filter and fluid . 9
8.2.3 Filter use .10
8.3 Filtration process definition .10
8.4 Integrity testing process definition .11
9 Validation .12
9.1 General .12
9.2 Validation of fluid-specific microbial retention by sterilizing filters for liquids .12
9.2.1 General.12
9.2.2 Test organism .13
9.3 Validation of the integrity test for sterilizing filters for liquids .14
9.4 Validation of filter interactions with the process fluid .15
9.5 Validation of the sterilization of filter system .15
9.6 Validation of fluid-specific microbial retention by sterilizing filters for gases .15
9.6.1 General.15
9.6.2 Aerosol retention .15
9.6.3 Validation of physical integrity testing .15
9.6.4 Compatibility and service life .16
9.6.5 Validation of the sterilization of the filter system for gases .16
10 Routine monitoring and control .16
11 Product release from sterilizing filtration .16
12 Maintaining process effectiveness .17
12.1 General .17
12.2 Recalibration .17
© ISO 2018 – All rights reserved iii
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SIST EN ISO 13408-2:2018
ISO 13408-2:2018(E)
12.3 Maintenance of equipment .17
12.4 Requalification .17
12.5 Assessment of change .18
Annex A (informative) Guidance on the application of this document .19
Bibliography .34
iv © ISO 2018 – All rights reserved
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SIST EN ISO 13408-2:2018
ISO 13408-2:2018(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
...
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