EN ISO 13408-1:2015

SLOVENSKI STANDARD
01-september-2015
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SIST EN ISO 13408-1:2011
SIST EN ISO 13408-1:2011/A1:2013
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Aseptic processing of health care products - Part 1: General requirements (ISO 13408-
1:2008, including Amd 1:2013)
Aseptische Herstellung von Produkten für die Gesundheitsfürsorge - Teil 1: Allgemeine
Anforderungen (ISO 13408-1:2008)
Traitement aseptique des produits de santé - Partie 1: Exigences générales (ISO 13408-
1:2008, y compris Amd 1:2013)
Ta slovenski standard je istoveten z: EN ISO 13408-1:2015
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.

EUROPEAN STANDARD
EN ISO 13408-1
NORME EUROPÉENNE
EUROPÄISCHE NORM
June 2015
ICS 11.080.01 Supersedes EN ISO 13408-1:2011
English Version
Aseptic processing of health care products - Part 1: General
requirements (ISO 13408-1:2008, including Amd 1:2013)
Traitement aseptique des produits de santé - Partie 1: Aseptische Herstellung von Produkten für die
Exigences générales (ISO 13408-1:2008, y compris Amd Gesundheitsfürsorge - Teil 1: Allgemeine Anforderungen
1:2013) (ISO 13408-1:2008, einschließlich Amd 1:2013)
This European Standard was approved by CEN on 20 May 2015.

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, 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: Avenue Marnix 17, B-1000 Brussels
© 2015 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 13408-1:2015 E
worldwide for CEN national Members.

Contents Page
Foreword . 2
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on active implantable medical devices . 4
Annex ZB (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices . 5
Annex ZC (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devices . 6

Foreword
The text of ISO 13408-1:2008, including Amd 1:2013 has been prepared by Technical Committee
ISO/TC 198 “Sterilization of health care products” of the International Organization for Standardization
(ISO) and has been taken over as EN ISO 13408-1:2015 by 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 December 2015, and conflicting national standards shall
be withdrawn at the latest by December 2015.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent
rights.
This document supersedes EN ISO 13408-1:2011.
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 Directives.
For relationship with EU Directives, see informative Annexes ZA, ZB and ZC, which are integral parts 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
Annex 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 Equivalent dated standard
as listed in Clause 2 of the ISO
EN ISO
standard
ISO 9001 EN ISO 9001:2008 ISO 9001:2008
ISO 11135 EN ISO 11135:2014 ISO 11135:2014
ISO 11137-1 EN ISO 11137-1:2006 + A1:2013 ISO 11137-1:2006 + A1:2013
ISO 11137-2 EN ISO 11137-2:2013 ISO 11137-2:2013
ISO 13408-2 EN ISO 13408-2:2011 ISO 13408-2:2011
ISO 13408-3 EN ISO 13408-3:2011 ISO 13408-3:2011
ISO 13408-4 EN ISO 13408-4:2011 ISO 13408-4:2011
ISO 13408-5 EN ISO 13408-5:2011 ISO 13408-5:2011
ISO 13408-6 EN ISO 13408-6:2011 + A1:2013 ISO 13408-6:2011 + A1:2013
Normative references Equivalent dated standard
as listed in Clause 2 of the ISO
EN ISO
standard
ISO 13485 EN ISO 13485:2012 ISO 13485:2003
ISO 14160 EN ISO 14160:2011 ISO 14160:2011
ISO 14644-1 EN ISO 14644-1:1999 ISO 14644-1:1999
ISO 14644-2 EN ISO 14644-2:2000 ISO 14644-2:2000
ISO 14644-3 EN ISO 14644-3:2005 ISO 14644-3:2005
ISO 14644-4 EN ISO 14644-4:2001 ISO 14644-4:2001
ISO 14644-5 EN ISO 14644-5:2004 ISO 14644-5:2004
ISO 14644-7 EN ISO 14644-7:2004 ISO 14644-7:2004
ISO 14698-1 EN ISO 14698-1:2003 ISO 14698-1:2003
ISO 14698-2 EN ISO 14698-2:2003 + A1:2006 ISO 14698-2:2003 + A1:2006
ISO 14937 EN ISO 14937:2009 ISO 14937:2009
ISO 14971 EN ISO 14971:2012 ISO 14971:2007
ISO 17665-1 EN ISO 17665-1:2006 ISO 17665-1:2006
ISO 20857 EN ISO 20857:2013 ISO 20857:2013
Regarding the reference to ICH Q9: Guidance for Industry — Quality Risk Management, this should be
considered to be the edition published in 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, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United
Kingdom.
Endorsement notice
The text of ISO 13408-1:2008, including Amd 1:2013 has been approved by CEN as EN ISO 13408-1:2015
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
This European Standard has been prepared under a mandate given to CEN/CENELEC by the European
Commission and the European Free Trade Association to provide a means of conforming to Essential
Requirements of the New Approach Directive 90/385/EEC on active implantable medical devices.
Once this standard is cited in the Official Journal of the European Union under that Directive and has been
implemented as a national standard in at least one Member State, compliance with the 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 Directive 90/385/EEC
Clauses of this EN Essential Requirements Qualifying remarks/Notes
(ERs) of Directive
90/385/EEC
4,5,6,7,8,9,10,11 7 Only attainment of sterility by aseptic processing
is considered by this standard.
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 are not covered.
WARNING — Other requirements and other EU Directives may be applicable to the product(s) 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
This European Standard has been prepared under a mandate given to CEN/CENELC by the European
Commission and the European Free Trade Association to provide a means of conforming to Essential
Requirements of the New Approach Directive 93/42/EEC on medical devices.
Once this standard is cited in the Official Journal of the European Union under that Directive and has been
implemented as a national standard in at least one Member State, compliance with the 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 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 ZB.1 — Correspondence between this European Standard and Directive 93/42/EEC
Clauses of this EN Essential Requirements Qualifying remarks/Notes
(ERs) of Directive 93/42/EEC
4,5,6,7,8,9,10,11 8.3 Only attainment of sterility by aseptic processing
is considered by this standard.
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 are not covered.
4,5,6,7,8,9,10,11 8.4 This relevant Essential Requirement is only partly
addressed in this European Standard. Aspects of
manufacture other than those related to
sterilization are not covered.
WARNING — Other requirements and other EU Directives may be applicable to the product(s) 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
This European Standard has been prepared under a mandate given to CEN/CENELEC by the European
Commission and the European Free Trade Association to provide a means of conforming to Essential
Requirements of the New Approach Directive 98/79/EC on in vitro diagnostic medical devices.
Once this standard is cited in the Official Journal of the European Union under that Directive and has been
implemented as a national standard in at least one Member State, compliance with the 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 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 ZC.1 — Correspondence between this European Standard and Directive 98/79/EC
Clauses of this EN Essential Requirements (ERs) of Qualifying remarks/Notes
Directive 98/79/EC
4,5,6,7,8,9,10,11 B.2.3 Only attainment of sterility by
aseptic processing is considered
by this standard.
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 are not covered.
4,5,6,7,8,9,10,11 B.2.4 This relevant Essential requirement
is addressed in this International
Standard only with regard to:
- sterilization, not covering other
special microbiological state
- devices for which aseptic
processing is appropriate
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this Standard.

INTERNATIONAL ISO
STANDARD 13408-1
Second edition
2008-06-15
Aseptic processing of health care
products —
Part 1:
General requirements
Traitement aseptique des produits de santé —
Partie 1: Exigences générales
Reference number
ISO 13408-1:2008(E)
©
ISO 2008
ISO 13408-1:2008(E)
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ii © ISO 2008 – All rights reserved

ISO 13408-1:2008(E)
Contents Page
Foreword. v
Introduction . vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions. 2
4 Quality system elements. 7
4.1 General. 7
4.2 Assignment of responsibilities . 7
4.3 Calibration . 7
5 Aseptic process definition. 8
5.1 General. 8
5.2 Risk management . 8
6 Manufacturing environment . 10
6.1 General. 10
6.2 Manufacturing environment design. 11
6.3 Layout . 12
6.4 Material and personnel flow . 14
6.5 HVAC system . 15
6.6 Cleanroom qualification. 17
6.7 Utility services and ancillary equipment . 17
6.8 Environmental and personnel monitoring programmes . 17
7 Equipment . 21
7.1 Qualification . 21
7.2 Maintenance of equipment . 23
8 Personnel. 23
8.1 General. 23
8.2 Training for APA qualification . 24
8.3 Gowning procedures. 25
8.4 General employee health . 26
9 Manufacture of the product . 27
9.1 Attainment and maintenance of sterility . 27
9.2 Duration of the manufacturing process .27
9.3 Aseptic manufacturing procedures . 28
9.4 Cleaning and disinfection of facilities . 28
9.5 Cleaning, disinfection and sterilization of equipment . 30
10 Process simulation. 31
10.1 General. 31
10.2 Media selection and growth support . 32
10.3 Simulation procedures. 32
10.4 Incubation and inspection of media filled units . 33
10.5 Initial performance qualification . 33
10.6 Periodic performance requalification . 34
10.7 Repeat of initial performance qualification. 35
10.8 Documentation of process simulations . 35
10.9 Disposition of filled product . 36
11 Test for sterility. 37
ISO 13408-1:2008(E)
11.1 General . 37
11.2 Investigation of positive units from tests for sterility . 37
Annex A (informative) Example of a flow chart . 38
Annex B (informative) Typical elements of an aseptic process definition . 39
Annex C (informative) Examples of specific risks . 40
Annex D (informative) Comparison of classification of cleanrooms . 41
Annex E (informative) Specification for water used in the process. 42
Annex F (informative) Aseptic processing area . 44
Bibliography . 45

iv © ISO 2008 – All rights reserved

ISO 13408-1:2008(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies
(ISO member bodies). The work of preparing International Standards is normally carried out through ISO
technical committees. Each member body interested in a subject for which a technical committee has been
established has the right to be represented on that committee. International organizations, governmental and
non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the
International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
The main task of technical committees is to prepare International Standards. Draft International Standards
adopted by the technical committees are circulated to the member bodies for voting. Publication as an
International Standard requires approval by at least 75 % of the member bodies casting a vote.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. ISO shall not be held responsible for identifying any or all such patent rights.
ISO 13408-1 was prepared by Technical Committee ISO/TC 198, Sterilization of health care products.
This second edition cancels and replaces the first edition (ISO 13408-1:1998), which has been technically
revised. Any normative and informative clauses on subjects which have meanwhile been addressed in Part 2 to
Part 6 of ISO 13408 have been removed from this part.
ISO 13408 consists of the following parts, under the general title Aseptic processing of health care products:
⎯ Part 1: General requirements
⎯ Part 2: Filtration
⎯ Part 3: Lyophilization
⎯ Part 4: Clean-in-place technologies
⎯ Part 5: Sterilization in place
⎯ Part 6: Isolator systems
ISO 13408-1:2008(E)
Introduction
Health care products that are labelled “sterile” are prepared using appropriate and validated methods under
stringent control as part of a quality management system. For pharmaceuticals and medical devices there
might be various requirements including compliance with ISO standards, GMP regulations and
pharmacopoeial requirements.
Wherever possible, healthcare products intended to be sterile should be sterilized in their final sealed
container (terminal sterilization). ISO/TC 198 has prepared standards for terminal sterilization of health care
products by irradiation (series ISO 11137), by moist heat (ISO 17665-1), by dry heat (ISO 20857, in
preparation) and by ethylene oxide (ISO 11135-1).
When a health care product is intended to be sterile and cannot be terminally sterilized, aseptic processing
provides an alternative. Presterilization of product, product parts and/or components and all equipment
coming into direct contact with the aseptically-processed product is required. Aseptic processing intends to
maintain the sterility of the pre-sterilized components and products during assembling. The resulting product is
required to be sterile in its final container. Aseptic processing can also be used to prevent contamination of
biological product or biological systems (e.g. tissues, vaccines).
While terminal sterilization involves the control of a well-defined process of known lethality delivered to the
product and a sterility assurance level (SAL) can be extrapolated from sterilization data, this is not applicable
to aseptic processing.
Examples of applications in which aseptic processing are used include:
⎯ aseptic handling and filling of solutions, suspensions, semisolids and powders;
⎯ aseptic handling, transfer and packaging of solid products including solid medical devices;
⎯ aseptic handling, transfer and packaging of combination products;
⎯ aseptic handling of tissues or biological production systems.
Sterilization procedures which render components and/or parts sterile as a prerequisite for further aseptic
processing can be treated as separate procedures. They have to be evaluated and validated separately and it
is important that their risk of failure is minimal. The aseptic process definition encompasses all production
steps following the sterilization of product and components until the final container or package is sealed. To
keep the aseptic process definition clear and workable, this part of ISO 13408 is focused on the risks to the
maintenance of sterility.
It is important to control all possible sources of contamination in order to maintain the sterility of each and
every component. To achieve this, a risk-based aseptic process definition is established encompassing each
product and applied in a comprehensive way considering product, package design, environment and
manufacturing process designs. The product is processed in a controlled environment where microbial and
particulate levels are maintained at defined minimal levels and where human intervention is minimized.
Validated systems, adequately trained personnel, controlled environments and well-documented systematic
processes are applied to assure a sterile finished product.
The aseptic process is divided into unit operations (e.g. sterilization of product or components including sterile
filtration, assembly of components, handling and storage of sterilized product) and it is necessary that
potential sources of contamination from materials, components, product, personnel, facility, equipment and
utilities such as water systems be considered and minimized. Only if all risks of contamination have been
recognised, wherever possible minimized, eliminated or controlled and finally have been evaluated as
vi © ISO 2008 – All rights reserved

ISO 13408-1:2008(E)
acceptable, can the controls on the aseptic process be considered to be acceptable. Appropriate validation of
the specified elements of the aseptic process is needed, of which process simulation studies are an essential.
This revision of ISO 13408-1:1998 is intended to adopt this International Standard to the actual state of
technology in the field.
INTERNATIONAL STANDARD ISO 13408-1:2008(E)

Aseptic processing of health care products —
Part 1:
General requirements
1 Scope
1.1 This part of ISO 13408 specifies the general requirements for, and offers guidance on, processes,
programmes and procedures for development, validation and routine control of the manufacturing process for
aseptically-processed health care products.
1.2 This part of ISO 13408 includes requirements and guidance relative to the overall topic of aseptic
processing. Specific requirements and guidance on various specialized processes and methods related to
filtration, lyophilization, clean-in place (CIP) technologies, sterilization in place (SIP) and isolator systems are
given in other parts of ISO 13408.
NOTE This part of ISO 13408 does not supersede or replace national regulatory requirements, such as Good
Manufacturing Practices (GMPs) and/or pharmacopoeial requirements that pertain in particular national or regional
jurisdictions.
2 Normative references
The following referenced documents are indispensable for the application of this document. For dated
references, only the edition cited applies. For undated references, the latest edition of the referenced
document (including any amendments) applies.
ISO 9001, Quality management systems — Requirements
ISO 11135-1, Sterilization of health care products — Ethylene oxide — Part 1: Requirements for 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
ISO 11137-2, Sterilization of health care products — Radiation — Part 2: Establishing the sterilization dose
ISO 13408-2, Aseptic processing of health care products — Part 2: Filtration
ISO 13408-3, Aseptic processing of health care products — Part 3: Lyophilization
ISO 13408-4, Aseptic processing of health care products — Part 4: Clean-in-place technologies
ISO 13408-5, Aseptic processing of health care products — Part 5: Sterilization in place
ISO 13408-6, Aseptic processing of health care products — Part 6: Isolator systems
ISO 13485, Medical devices — Quality management systems — Requirements for regulatory purposes
ISO 14160, Sterilization of single-use medical devices incorporating materials of animal origin — Validation
and routine control of sterilization by liquid chemical sterilants
ISO 13408-1:2008(E)
ISO 14644-1:1999, Cleanrooms and associated controlled environments — Part 1: Classification of air
cleanliness
ISO 14644-2, Cleanrooms and associated controlled environments — Part 2: Specifications for testing and
monitoring to prove continued compliance with ISO 14644-1
ISO 14644-3, Cleanrooms and associated controlled environments — Part 3: Test methods
ISO 14644-4, Cleanrooms and associated controlled environments — Part 4: Design, construction and start-
up
ISO 14644-5, Cleanrooms and associated controlled environments — Part 5: Operations
ISO 14644-7, Cleanrooms and associated controlled environments — Part 7: Separative devices (clean air
hoods, gloveboxes, isolators and mini-environments)
ISO 14698-1, Cleanrooms and associated controlled environments — Biocontamination control — Part 1:
General principles and methods
ISO 14698-2, Cleanrooms and associated controlled environments — Biocontamination control — Part 2:
Evaluation and interpretation of biocontamination data
ISO 14937, Sterilization of health care products — General requirements for characterization of a sterilizing
agent and the development, validation and routine control of a sterilization process for medical devices
ISO 14971, Medical devices — Application of risk management to medical devices
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)
ISO 20857 , Sterilization of health care products — Dry heat — Requirements for the development, validation
and routine control of a sterilization process for medical devices
2)
ICH Guidance for Industry — Q9 Quality Risk Management
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply:
3.1
action level
established microbial or particulate monitoring results requiring immediate follow-up and corrective action
3.2
airlock
room with interlocked doors designed to maintain pressure control between adjacent rooms of different
cleanliness class
3.3
alert level
established microbial or particulate monitoring results giving early warning of potential drift from normal
operating conditions which are not necessarily grounds for definitive corrective action but which could require
follow-up investigation
1) To be published.
2) Available at: http://www.ich.org
2 © ISO 2008 – All rights reserved

ISO 13408-1:2008(E)
3.4
aseptic processing
handling of sterile product, containers and/or devices in a controlled environment, in which the air supply,
materials, equipment and personnel are regulated to maintain sterility
NOTE This includes sterilization by membrane filtration which cannot be separated from the subsequent aseptic
process.
3.5
aseptic processing area
APA
facilities for aseptic processing (3.4), consisting of several zones
3.6
bioburden
population of viable microorganisms on or in product and/or sterile barrier system
[ISO/TS 11139:2006, definition 2.2]
NOTE For the purposes of aseptic processing, the bioburden of concern is that on or in the product including all
factors affecting it such as raw material, intermediates, other components and equipment.
3.7
bio-decontamination
removal of microbiological contamination or its reduction to an acceptable level
[ISO 13408-6:2005, definition 3.1]
3.8
cleaning
removal of contamination from an item to the extent necessary for further processing or for intended use
[ISO/TS 11139:2006, definition 2.7]
3.9
combination product
product comprised of drug/device, biologic/device, drug/biologic or drug/device/biologic, that are physically,
chemically, or otherwise combined or mixed and produced as a single entity
3.10
correction
action to eliminate a detected nonconformity
NOTE A correction can be made in conjunction with a corrective action.
[ISO 9000:2005; definition 3.6.6]
3.11
corrective action
action to eliminate the cause of a detected nonconformity or other undesirable situation
[ISO 9000:2005, definition 3.6.5]
NOTE 1 There can be more than one cause for a nonconformity.
NOTE 2 Corrective action is taken to prevent recurrence whereas preventive action (3.29) is taken to prevent
occurrence.
NOTE 3 There is a distinction between correction and corrective action.
NOTE 4 Corrective actions might be subject to change control.
ISO 13408-1:2008(E)
3.12
critical processing zone
location within the aseptic processing area in which product and critical surfaces are exposed to the
environment
3.13
critical surface
surface that may come into contact with or directly affect a product or its containers or closures
3.14
depyrogentation
validated process designed to remove or deactivate endotoxins
3.15
design qualification
verification that the proposed specification for the facility, equipment or system is suitable for the intended use
[ISO/TS 11139:2006, definition 2.12]
3.16
direct support zone
protective area directly surrounding a critical processing zone
3.17
disinfectant
chemical agent that is able to reduce the number of viable microorganisms
3.18
disinfection
removal, destruction or de-activation of microorganisms on objects or surfaces
[ISO 14644-5:2004;definition 3.1.4]
3.19
endotoxin
lipopolysaccharide component of the cell wall of Gram-negative bacteria which is heat stable and elicits a
variety of inflammatory responses in animals and humans
3.20
environmental isolates
microorganisms present in and/or isolated from processing or manufacturing environments
3.21
gowning procedure
defined steps to reduce the risk of contamination while putting on the protective garments needed to enter the
APA (3.5)
3.22
health care product
medical device(s), including in vitro diagnostic medical device(s), or medicinal product(s), including
biopharmaceutical(s)
[ISO/TS 11139:2006, definition 2.20]
3.23
high efficiency particulate air filter
HEPA filter
retentive matrix having a minimum particle-collection efficiency of 99,97 % (that is, a maximum particle
penetration of 0,03 % for 0,3 µm particles)
4 © ISO 2008 – All rights reserved

ISO 13408-1:2008(E)
3.24
indirect support zone
location within the aseptic processing area which protects the direct support zone
NOTE The required grade of cleanliness of the indirect support zone depends on the aseptic processing activities
performed in the indirect processing zone.
3.25
installation qualification
IQ
process of obtaining and documenting evidence that equipment has been provided and installed in
accordance with its specification
[ISO/TS 11139:2006, definition 2.22]
3.26
isolator
enclosure capable of preventing ingress of contaminants by means of physical interior/exterior separation, and
capable of being subject to reproducible interior bio-decontamination
NOTE An isolator can range in size from a small box to a large room.
3.27
operational qualification
OQ
process of obtaining and documenting evidence that installed equipment operates within predetermined limits
when used in accordance with its operational procedures
[ISO/TS 11139:2006, definition 2.27]
3.28
performance qualification
PQ
process of obtaining and documenting evidence that the equipment, as installed and operated in accordance
with operational procedures, consistently performs in accordance with predetermined criteria and thereby
yields product meeting its specification
[ISO/TS 11139:2006, definition 2.30]
3.29
preventive action
action to eliminate the cause of a potential nonconformity or other undesirable potential situation
[ISO 9000:2005, definition 3.6.4]
NOTE 1 There can be more than one cause for a potential nonconformity.
NOTE 2 Preventive action is taken to prevent occurrence whereas corrective action (3.11) is taken to prevent
recurrence.
3.30
qualification
documented process used by the health care product manufacturer to assure the reliability and capability of
equipment and/or processes before approval for use in manufacturing
NOTE Qualification of equipment and/or proces
...