SIST EN ISO 13408-2:2018

SLOVENSKI STANDARD
01-julij-2018
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SIST EN ISO 13408-2:2011
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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
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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.

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

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
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.
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.
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.
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.
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
ISO 13408-2:2018(E)
© ISO 2018
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
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Published in Switzerland
ii © ISO 2018 – All rights reserved

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 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

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 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 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 the following
URL: www.iso.org/iso/foreword.html.
This document was prepared by Technical Committee ISO/TC 198, Sterilization of health care products.
This second edition cancels and replaces the first edition (ISO 13408-2:2003), which has been
technically revised.
A list of all parts in the ISO 13408 series can be found on the ISO website.
ISO 13408-2:2018(E)
Introduction
ISO 13408-1 covers general aspects of aseptic processing. Several processes including sterilizing
filtration, lyophilization, clean and sterilization in place, isolator systems, and alternative processes for
medical devices and combination products were found to be in need of supplementary information,
which was too extensive to be included in the corresponding annexes to ISO 13408-1. This information
is presented in ISO 13408-2 to ISO 13408-7.
Sterilizing filtration is a critical step in an aseptic manufacturing process. Validation of sterilizing
filtration processes can be complex and is generally conducted in both a process and product specific
manner. This document describes requirements that, if met, will provide a sterilizing filtration process
that consistently removes microorganisms from a fluid (liquid or gas) without negatively affecting
the quality of the filtrate. Furthermore, conformity with the requirements ensures that a sterilizing
filtration process is both reliable and reproducible so that a determination can be made, with reasonable
confidence, that the sterilizing grade filter/s will provide a sterile filtrate under specified operational
conditions. This (the reliability and reproducibility of the filtration process) is essential, as unlike a
micro-biocidal sterilization process where process variables can be monitored continuously, microbial
retention and physical integrity of a sterilising grade filter cannot be monitored on a continuous basis
throughout a filtration process.
Where validation establishes a reproducible relationship between the product-specific bacterial
retention capability of a sterilizing grade filter and the physical integrity of that filter, then suitable
non-destructive pre-use and post-use filter integrity tests are used to determine whether a full-scale
sterilizing filtration process has been conducted successfully. During terminal sterilization the kinetics
of inactivation follows a mathematical order and allow calculation of a sterility assurance level (SAL).
Removal of organisms from a fluid by filtration does not follow such mathematical order and so the use
of the term “sterility assurance level” is not appropriate for product sterilized by filtration.
There has been a significant increase in the development and availability of biopharmaceuticals,
biologic-based medical devices and cell-based health care products since publication of the initial 2003
edition of this document. This second edition emphasizes the importance of a thorough understanding
of the nature of the indigenous bioburden of a fluid that is to be sterilized by filtration, including
its relationship to the test microorganism used to determine microbial retention capability of the
sterilizing grade filter. For example, Mycoplasma can cause serious contamination problems during the
manufacturing of biopharmaceutical, biotechnological and cell-based health care products. A thorough
understanding of the indigenous bioburden enables suitable safeguards to be implemented during
development, validation and control of a sterilizing filtration process to ensure the safety and quality of
the filtered fluid.
While the activities required by this document have been grouped together and are presented in a
particular order, this document does not require that the activities be performed in the order that they
are presented. The activities required are not necessarily sequential, as the programme of development
and validation may be iterative. It is possible that performing these different activities will involve a
number of separate individuals and/or organizations, each of whom undertake one or more of these
activities. This document does not specify the particular individuals or organizations to carry out the
activities.
Guidance on the application of this document is given in Annex A.
vi © ISO 2018 – All rights reserved

INTERNATIONAL STANDARD ISO 13408-2:2018(E)
Aseptic processing of health care products —
Part 2:
Sterilizing filtration
1 Scope
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.
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 11135, Sterilization of health-care products — Ethylene oxide — Requirements for the development,
validation and routine control of a sterilization process for medical devices
ISO 11137-1, Sterilization of health care products — Radiation — Part 1: Requirements for development,
validation and routine control of a sterilization process for medical devices
1)
ISO 11139, Sterilization of health care products — Vocabulary — Terms used in sterilization and related
equipment and process standards
ISO 13408-1:2008, Aseptic processing of health care products — Part 1: General requirements
ISO 13408-1:2008/Amd. 1:2013, Aseptic processing of health care products — Part 1: General requirements
— Amendment 1
ISO 13408-5, Aseptic processing of health care products — Part 5: Sterilization in place
ISO 13485, Medical devices — Quality management systems — Requirements for regulatory purposes
ISO 17665-1, Sterilization of health care products — Moist heat — Part 1: Requirements for the development,
validation and routine control of a sterilization process for medical devices
1) Under preparation. Stage at the time of publication: ISO/DIS 11139:2017(E).
ISO 13408-2:2018(E)
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 11139 and the following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— IEC Electropedia: available at https://www.electropedia.org/
— ISO Online browsing platform: available at https://www.iso.org/obp
3.1
bacterial challenge test
technical operation performed to evaluate the capability of a filter (3.5) to retain organisms from liquid
bacterial suspension under defined conditions
3.2
bioburden
population of viable microorganisms (3.9) on or in product and/or sterile barrier system
Note 1 to entry: For the purposes of this document, the definition of bioburden is the population of viable
microorganisms in a fluid (3.6) prior to sterilizing filtration (3.11).
3.3
chemical compatibility
capability of process fluids (3.6) and filter (3.5) materials to be used together, under the
specified process conditions, without adverse effects on either the fluids or filter materials
3.4
extractable
substance that can be released from a filter (3.5) or material using extraction solvents and/or extraction
conditions that are expected to be at least as aggressive as the normal use conditions
[SOURCE: ISO 10993-12:2012, 3.8, modified — The wording has been modified.]
3.5
filter
construct of porous material through which a fluid (3.6) is passed to remove viable and/or non-viable
particles
3.6
fluid
substance that continually deforms (flows) under applied shear force
EXAMPLE Liquid, gas, vapour or plasma.
Note 1 to entry: The filtrate of the fluid subjected to the sterilizing filtration (3.11) process might be the product
to be produced, a part of the formulation, a gas used to provide overpressure or a process gas released into the
aseptic processing area (e.g. gases released from air actuated valves).
3.7
filter integrity test
non-destructive physical test that can be correlated to the bacterial retention capability of a filter
assembly
3.8
leachable
substance that can be released from a filter (3.5) or filter assembly during normal use conditions
3.9
microorganism
entity of microscopic size, encompassing bacteria, fungi, protozoa and viruses
Note 1 to entry: Viruses are not addressed in this document.
2 © ISO 2018 – All rights reserved

ISO 13408-2:2018(E)
3.10
pore size rating
nominal pore size of a filter (3.5) as claimed and stated in the labelling
Note 1 to entry: The pore size rating is determined by retention performance with a model particle. The pore
size rating is not necessarily the physical diameter of the pores but is a rating based on the size of particles which
might not pass through the filter.
3.11
sterilizing filtration
removal of viable microorganisms (3.9) from fluids (3.6) by passage of the fluid through a filter (3.5)
under specified process conditions resulting in a sterile filtrate
4 Quality system elements
4.1 General
A quality management system as defined in ISO 13408-1:2008, Clause 4, and
ISO 13408-1:2008/Amd. 1:2013 shall be implemented to ensure control over all activities affecting
sterilizing filtration. Additionally the requirements in 4.2 and 4.3 shall apply.
4.2 Management responsibility
Operator training specific to filtration activities shall be implemented and documented for the
following:
a) filtration procedures, modes of failure and needed precautions;
b) integrity test theory and practice;
c) failure investigation procedures and measures taken in case of integrity test deviations;
d) filter assembly procedure (including aseptic technique if required);
e) filter installation, cleaning and sterilization procedures.
4.3 Procurement of filters
4.3.1 Procedures for purchasing filters and filtration equipment shall be specified. These procedures
shall conform with the applicable clauses of ISO 13485 or equivalent quality system.
4.3.2 There shall be a written agreement between the filter user and filter manufacturer that the
filter manufacturer will notify the filter user of any changes in the filter manufacturing conditions with
potential to affect the defined fluid and process parameters.
4.3.3 Procedures for identification and traceability of filters shall be specified. These procedures shall
conform with the applicable clauses of ISO 13485 or equivalent quality system.
5 Sterilizing filter characterization
5.1 General
Sterilizing filter characterization is the process of determining which filters might be suitable for use
as a sterilizing filter in a sterilizing filtration process for a given fluid. This is usually carried out by the
filter user considering information available from the filter manufacturer.
ISO 13408-2:2018(E)
Sterilizing filter formats include, but are not limited to the following:
a) membrane filter discs for the user to assemble into filter holders/housings;
b) cartridge filters for the user to assemble into filter holders/housings;
c) units supplied pre-assembled by the filter manufacturer (capsules).
The specification for the filters used in production shall be justified against the specification of those
used in the product and process validation.
5.2 Microbial removal effectiveness
5.2.1 Microbial removal effectiveness data shall be developed for each combination of sterilizing grade
filter and fluid type. This is usually by demonstration of retention of a
a) product specific microbial challenge for liquid filtration, and
b) generic aerosol challenge for gas filtration.
5.2.2 The variables that affect the effectiveness of the microbial removal and the interactions of these
variables in relation to this effectiveness shall be identified. Such variables include, but are not limited to
the following:
a) filter membrane characteristics, such as the pore size distribution, surface chemistry, structure
and polymer type of the membrane (see 8.2.1);
b) filtration equipment characteristics (see 6.4);
c) fluid characteristics, such as the effects of surfactants or additives; including the absorptive
influence of the fluid on microorganisms, pH, viscosity, osmolarity, surface tension and ionic
strength (see 7.1.2);
d) fluid bioburden; number, type and cell size of organisms present in the fluid and process conditions
or formulations which might affect cell size (see 7.1.2);
e) process conditions, such as batch size, temperature, differential pressure, flow rate, hold times and
processing times (see 8.3.1);
f) the effect of the sterilization process for the filter on the filter performance.
For the sterilization of gases by filtration, some of the above may not be applicable.
5.3 Material effects
5.3.1 The effects of materials extracted or leached from the filter on the fluids being filtered shall be
evaluated (see 8.2.2.2 and 8.2.2.3).
5.3.2 The effect
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