SIST EN ISO 13408-1:2011
(Main)Aseptic processing of health care products - Part 1: General requirements (ISO 13408-1:2008)
Aseptic processing of health care products - Part 1: General requirements (ISO 13408-1:2008)
ISO 13408-1:2008 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.
ISO 13408-1:2008 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.
Aseptische Herstellung von Produkten für die Gesundheitsfürsorge - Teil 1: Allgemeine Anforderungen (ISO 13408-1:2008)
1.1 Der vorliegende Teil von ISO 13408 legt die allgemeinen Anforderungen an Verfahren, Programme und Verfahrensweisen zur Entwicklung, Validierung und Routinekontrolle des Herstellungsverfahrens für aseptisch hergestellte Produkte für die Gesundheitsfürsorge fest und stellt einen Leitfaden dafür zur Verfügung.
1.2 Der vorliegende Teil von ISO 13408 umfasst Anforderungen und einen Leitfaden in Bezug auf das Gesamtthema der aseptischen Herstellung. Besondere Anforderungen und ein Leitfaden für verschiedene spezielle Prozesse und Verfahren in Bezug auf Filtration, Lyophilisierung, Technologien der Reinigung vor Ort (en: cleaning in place, CIP), Sterilisation vor Ort (en: sterilization in place, SIP) und Isolatorsysteme sind in anderen Teilen von ISO 13408 angeführt.
ANMERKUNG Der vorliegende Teil von ISO 13408 ersetzt keine nationalen behördlichen Anforderungen, wie z. B. Gute Herstellungspraktiken (GMP) und/oder Anforderungen von Arzneibüchern, die insbesondere nationale oder regionale Zuständigkeiten betreffen.
Traitement aseptique des produits de santé - Partie 1: Exigences générales (ISO 13408-1:2008)
L'ISO 13408-1:2008 sp�cifie des exigences g�n�rales et propose des directives en mati�re de m�thodes, de programmes et de modes op�ratoires pour le d�veloppement, la validation et le contr�le de produits de sant� soumis � un traitement aseptique.
L'ISO 13408-1:2008 comprend des exigences et des directives relatives au domaine g�n�ral du traitement aseptique. Des exigences et des directives sp�cifiques sur les divers proc�d�s et m�thodes sp�cialis�s de filtration, de lyophilisation, de nettoyage in situ, de st�rilisation in situ et de syst�mes isolateurs sont indiqu�es dans les diff�rentes parties de l'ISO 13408.
Aseptična proizvodnja izdelkov za zdravstveno nego - 1. del: Splošne zahteve (ISO 13408-1:2008)
Ta del ISO 13408 določa splošne zahteve in ponuja smernice za procese, programe in postopke za razvoj, validacijo in rutinsko kontrolo proizvodnega procesa za aseptično proizvedene izdelke za zdravstveno nego. Ta del ISO 13408 vključuje zahteve in smernice, ki se nanašajo na celovito temo aseptične proizvodnje. Določene zahteve in smernice za različne specializirane procese in metode, povezane s filtracijo, liofilizacijo, tehnologijami čiščenja na mestu proizvodnje (CIP), sterilizacijo na mestu proizvodnje (SIP) in sistemom izolatorjev, so podane v drugih delih ISO 13408.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 13408-1:2011
01-oktober-2011
1DGRPHãþD
SIST EN 13824:2005
$VHSWLþQDSURL]YRGQMDL]GHONRY]D]GUDYVWYHQRQHJRGHO 6SORãQH]DKWHYH ,62
Aseptic processing of health care products - Part 1: General requirements (ISO 13408-
1:2008)
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)
Ta slovenski standard je istoveten z: EN ISO 13408-1:2011
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
SIST EN ISO 13408-1:2011 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 13408-1:2011
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SIST EN ISO 13408-1:2011
EUROPEAN STANDARD
EN ISO 13408-1
NORME EUROPÉENNE
EUROPÄISCHE NORM
June 2011
ICS 11.080.01 Supersedes EN 13824:2004
English Version
Aseptic processing of health care products - Part 1: General
requirements (ISO 13408-1:2008)
Traitement aseptique des produits de santé - Partie 1: Aseptische Herstellung von Produkten für die
Exigences générales (ISO 13408-1:2008) Gesundheitsfürsorge - Teil 1: Allgemeine Anforderungen
(ISO 13408-1:2008)
This European Standard was approved by CEN on 10 June 2011.
CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European
Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such national
standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by translation
under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management Centre has the same
status as the official versions.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland,
Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2011 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 13408-1:2011: E
worldwide for CEN national Members.
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SIST EN ISO 13408-1:2011
EN ISO 13408-1:2011 (E)
Contents Page
Foreword .3
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
2
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SIST EN ISO 13408-1:2011
EN ISO 13408-1:2011 (E)
Foreword
The text of ISO 13408-1:2008 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 13408-1:2011 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 2011, and conflicting national standards shall be withdrawn
at the latest by December 2011.
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 13824:2004.
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, or ZC, which are integral parts of this
document.
According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following
countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech
Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia,
Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain,
Sweden, Switzerland and the United Kingdom.
Endorsement notice
The text of ISO 13408-1:2008 has been approved by CEN as a EN ISO 13408-1:2011 without any
modification.
3
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SIST EN ISO 13408-1:2011
EN ISO 13408-1:2011 (E)
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 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 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.
Table ZA.1 — Correspondence between this European Standard and Directive 90/385/EEC
Clauses of this EN Essential Requirements (ERs) of Qualifying remarks/Notes
Directive 90/385/EEC
4,5,6,7,8,9,10,11,12 7 This relevant Essential Requirement is
only partly addressed in this European
Standard
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this Standard.
4
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SIST EN ISO 13408-1:2011
EN ISO 13408-1:2011 (E)
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 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 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.
Table ZB.1 — Correspondence between this European Standard and Directive 93/42/EEC
Clauses of this EN Essential Requirements (ERs) of Qualifying remarks/Notes
Directive 93/42/EEC
4,5,6,7,8,9,10,11,12 8.3 This relevant Essential Requirement is
only partly addressed in this European
Standard
4,5,6,7,8,9,10,11,12 8.4
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this Standard.
5
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SIST EN ISO 13408-1:2011
EN ISO 13408-1:2011 (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
This European Standard has been prepared under a mandate given to CEN 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 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.
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
4,5,6,7,8,9,10,11,12 B.2.3 This relevant Essential Requirement is
only partly addressed in this European
Standard
4,5,6,7,8,9,10,11,12 B.2.4
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this Standard.
6
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SIST EN ISO 13408-1:2011
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
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SIST EN ISO 13408-1:2011
ISO 13408-1:2008(E)
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ii © ISO 2008 – All rights reserved
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SIST EN ISO 13408-1:2011
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 2008 – All rights reserved iii
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SIST EN ISO 13408-1:2011
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
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SIST EN ISO 13408-1:2011
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 2008 – All rights reserved v
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SIST EN ISO 13408-1:2011
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
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SIST EN ISO 13408-1:2011
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.
© ISO 2008 – All rights reserved vii
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SIST EN ISO 13408-1:2011
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SIST EN ISO 13408-1:2011
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 2008 – All rights reserved 1
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SIST EN ISO 13408-1:2011
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
...
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