SIST EN ISO 11137-2:2012
(Main)Sterilization of health care products - Radiation - Part 2: Establishing the sterilization dose (ISO 11137-2:2012)
Sterilization of health care products - Radiation - Part 2: Establishing the sterilization dose (ISO 11137-2:2012)
This part of ISO 11137 specifies methods for determining the minimum dose needed to achieve a specified requirement for sterility and methods to substantiate the use of 25 kGy or 15 kGy as the sterilization dose to achieve a sterility assurance level, SAL, of 10–6. This part of ISO 11137 also specifies methods of sterilization dose audit used to demonstrate the continued effectiveness of the sterilization dose. This part of ISO 11137 defines product families for sterilization dose establishment and sterilization dose audit.
Sterilisation von Produkten für die Gesundheitsfürsorge - Strahlen - Teil 2: Festlegung der Sterilisationsdosis (ISO 11137-2:2012)
Im vorliegenden Teil von ISO 11137 werden Verfahren zur Ermittlung der Mindestdosis, die zur Erfüllung einer
festgelegten Anforderung an die Sterilität erforderlich ist, sowie Verfahren zur Bestätigung der Anwendung
von 25 kGy oder 15 kGy als Sterilisationsdosis zur Erzielung eines Sterilitätssicherheitsniveaus, SAL, von
10−6 festgelegt. Dieser Teil von ISO 11137 legt auch Überprüfungsverfahren für die Sterilisationsdosis zum
Nachweis der fortgesetzten Wirksamkeit der Sterilisationsdosis fest.
Dieser Teil von ISO 11137 definiert Produktfamilien für die Festlegung der Sterilisationsdosis und die
Überprüfungen der Sterilisationsdosis.
Stérilisation des produits de santé - Irradiation - Partie 2: Établissement de la dose stérilisante (ISO 11137-2:2012)
L'ISO 11137-2:2011 spécifie des méthodes de détermination de la dose minimale nécessaire pour atteindre une exigence spécifiée de stérilité et des méthodes pour justifier l'utilisation de la dose stérilisante de 25 kGy ou de la dose stérilisante de 15 kGy, pour obtenir un niveau d'assurance de la stérilité, NAS, de 10-6. L'ISO 11137-2:2011 spécifie aussi des méthodes d'audit de la dose stérilisante utilisées pour démontrer l'efficacité continue de la dose stérilisante.
L'ISO 11137-2:2011 définit des familles de produits pour l'établissement de la dose stérilisante et l'audit de la dose stérilisante.
Sterilizacija izdelkov za zdravstveno nego - Sevanje - 2. del: Določanje odmerka sterilizacije (ISO 11137-2:2012)
Ta del standarda ISO 11137 določa metode za določanje minimalnega odmerka, ki je potreben za doseganje določene zahteve glede sterilnosti, in metode za utemeljitev uporabe 25 kGy ali 15 kGy kot odmerka sterilizacije za doseganje ravni zagotavljanja sterilnosti (SAL) 10–6. Ta del standarda ISO 11137 določa tudi metode za revizijo odmerka sterilizacije, ki se uporabljajo za dokaz stalne učinkovitosti odmerka sterilizacije. Ta del standarda ISO 11137 določa skupine izdelkov za določanje odmerka sterilizacije in revizijo odmerka sterilizacije.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 11137-2:2012
01-oktober-2012
1DGRPHãþD
SIST EN ISO 11137-2:2007
SIST EN ISO 11137-2:2007/AC:2009
6WHULOL]DFLMDL]GHONRY]D]GUDYVWYHQRQHJR6HYDQMHGHO 'RORþDQMHRGPHUND
VWHULOL]DFLMH ,62
Sterilization of health care products - Radiation - Part 2: Establishing the sterilization
dose (ISO 11137-2:2012)
Sterilisation von Produkten für die Gesundheitsfürsorge - Strahlen - Teil 2: Festlegung
der Sterilisationsdosis (ISO 11137-2:2012)
Stérilisation des produits de santé - Irradiation - Partie 2: Établissement de la dose
stérilisante (ISO 11137-2:2012)
Ta slovenski standard je istoveten z: EN ISO 11137-2:2012
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
SIST EN ISO 11137-2:2012 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 11137-2:2012
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SIST EN ISO 11137-2:2012
EUROPEAN STANDARD
EN ISO 11137-2
NORME EUROPÉENNE
EUROPÄISCHE NORM
March 2012
ICS 11.080.01 Supersedes EN ISO 11137-2:2007
English Version
Sterilization of health care products - Radiation - Part 2:
Establishing the sterilization dose (ISO 11137-2:2012)
Stérilisation des produits de santé - Irradiation - Partie 2: Sterilisation von Produkten für die Gesundheitsfürsorge -
Établissement de la dose stérilisante (ISO 11137-2:2012) Strahlen - Teil 2: Festlegung der Sterilisationsdosis (ISO
11137-2:2012)
This European Standard was approved by CEN on 14 March 2012.
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, Turkey and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2012 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 11137-2:2012: E
worldwide for CEN national Members.
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SIST EN ISO 11137-2:2012
EN ISO 11137-2:2012 (E)
Contents Page
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 11137-2:2012
EN ISO 11137-2:2012 (E)
Foreword
This document (EN ISO 11137-2:2012) 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 2012, and conflicting national standards shall be
withdrawn at the latest by September 2012.
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 11137-2:2007.
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, C, which is an integral part 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, Turkey and the United Kingdom.
Endorsement notice
The text of ISO 11137-2:2012 has been approved by CEN as a EN ISO 11137-2:2012 without any
modification.
3
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SIST EN ISO 11137-2:2012
EN ISO 11137-2:2012 (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 International Essential Requirements (ERs) of Qualifying remarks/Notes
Standard EU Directive 90/385/EEC
4, 5, 6, 7, 8, 9, 10 7 This relevant ER is only partly
addressed in this International
Standard and only in conjunction with
ISO 11137-1. Packaging for
maintenance of sterility during
transportation and storage are not
covered.
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 11137-2:2012
EN ISO 11137-2:2012 (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 EU Directive 93/42/EEC
Clauses of this International Essential Requirements (ERs) of Qualifying remarks/Notes
Standard EU Directive 93/42/EEC
4, 5, 6, 7, 8, 9, 10 8.3 This relevant ER is only partly
addressed in this International
Standard and only in conjunction with
ISO 11137-1. Packaging for
maintenance of sterility during
transportation and storage are not
covered.
4, 5, 6, 7, 8, 9, 10 8.4 This relevant ER is addressed in this
International Standard only in
conjunction with ISO 11137-1.
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 11137-2:2012
EN ISO 11137-2:2012 (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 International Essential Requirements (ERs) of Qualifying remarks/Notes
Standard EU Directive 98/79/EC
4, 5, 6, 7, 8, 9, 10 B.2.3 This relevant ER is only partly
addressed in this International
Standard and only in conjunction with
ISO 11137-1. Packaging for
maintenance of sterility during
transportation and storage are not
covered.
4, 5, 6, 7, 8, 9, 10 B.2.4 This relevant ER is only addressed in
this International Standard in
conjunction with ISO 11137-1.
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 11137-2:2012
INTERNATIONAL ISO
STANDARD 11137-2
Second edition
2012-03-15
Sterilization of health care products —
Radiation —
Part 2:
Establishing the sterilization dose
Stérilisation des produits de santé — Irradiation —
Partie 2: Établissement de la dose stérilisante
Reference number
ISO 11137-2:2012(E)
©
ISO 2012
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SIST EN ISO 11137-2:2012
ISO 11137-2:2012(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2012
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means,
electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or
ISO's member body in the country of the requester.
ISO copyright office
Case postale 56 CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail copyright@iso.org
Web www.iso.org
Published in Switzerland
ii © ISO 2012 – All rights reserved
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SIST EN ISO 11137-2:2012
ISO 11137-2:2012(E)
Contents Page
Foreword . v
Introduction . vi
1 Scope . 1
2 Normative references . 1
3 Terms, definitions and abbreviated terms . 1
3.1 Terms and definitions . 1
3.2 Abbreviated terms . 3
4 Definition and maintenance of product families for dose setting, dose substantiation and
sterilization dose auditing . 4
4.1 General . 4
4.2 Defining product families . 5
4.3 Designation of product to represent a product family for performance of a verification
dose experiment or sterilization dose audit . 5
4.4 Maintaining product families . 7
4.5 Effect of failure of establishment of sterilization dose or of a sterilization dose audit on a
product family . 7
5 Selection and testing of product for establishing the sterilization dose . 7
5.1 Nature of product . 7
5.2 Sample item portion (SIP) . 8
5.3 Manner of sampling . 9
5.4 Microbiological testing . 9
5.5 Irradiation . 10
6 Methods of dose establishment . 10
7 Method 1: dose setting using bioburden information . 11
7.1 Rationale . 11
7.2 Procedure for Method 1 for product with an average bioburden greater than or equal
to 1,0 for multiple production batches . 12
7.3 Procedure for Method 1 for product with an average bioburden greater than or equal
to 1,0 for a single production batch . 17
7.4 Procedure for Method 1 for product with an average bioburden in the range 0,1 to 0,9 for
multiple or single production batches . 19
8 Method 2: Dose setting using fraction positive information from incremental dosing to
determine an extrapolation factor . 20
8.1 Rationale . 20
8.2 Procedure for Method 2A . 21
8.3 Procedure for Method 2B . 24
9 Method VD — Substantiation of 25 kGy or 15 kGy as the sterilization dose . 28
max
9.1 Rationale . 28
25
9.2 Procedure for Method VD for multiple production batches . 29
max
25
9.3 Procedure for Method VD for a single production batch . 34
max
15
9.4 Procedure for Method VD for multiple production batches . 36
max
15
9.5 Procedure for Method VD for a single production batch . 40
max
10 Sterilization dose audit . 43
10.1 Purpose and frequency . 43
© ISO 2012 – All rights reserved iii
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SIST EN ISO 11137-2:2012
ISO 11137-2:2012(E)
10.2 Procedure for auditing a sterilization dose established using Method 1, Method 2A or
Method 2B .43
25
10.3 Procedure for auditing a sterilization dose substantiated using Method VD or
max
15
Method VD .46
max
10.4 Failure of a sterilization dose audit .50
11 Worked examples .50
11.1 Worked examples for Method 1 .50
11.2 Worked examples for Method 2 .53
11.3 Worked examples for Method VD .63
max
11.4 Worked example of a sterilization dose audit for a dose established using Method 1, the
findings from which necessitated augmentation of the sterilization dose.65
11.5 Worked example of a sterilization dose audit for a dose established using Method 2A, the
findings from which necessitated augmentation of the sterilization dose.66
11.6 Worked example of a sterilization dose audit for a sterilization dose substantiated using
25
Method VD .67
max
Bibliography .69
iv © ISO 2012 – All rights reserved
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SIST EN ISO 11137-2:2012
ISO 11137-2:2012(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 11137-2 was prepared by Technical Committee ISO/TC 198, Sterilization of health care products.
This second edition cancels and replaces the first edition (ISO 11137-2:2006), which has been technically
revised.
ISO 11137 consists of the following parts, under the general title Sterilization of health care products —
Radiation:
Part 1: Requirements for development, validation and routine control of a sterilization process for medical
devices
Part 2: Establishing the sterilization dose
Part 3: Guidance on dosimetric aspects
© ISO 2012 – All rights reserved v
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SIST EN ISO 11137-2:2012
ISO 11137-2:2012(E)
Introduction
This part of ISO 11137 describes methods that can be used to establish the sterilization dose in accordance
with one of the two approaches specified in 8.2 of ISO 11137-1:2006. The methods used in these approaches
are:
dose setting to obtain a product-specific dose;
dose substantiation to verify a preselected dose of 25 kGy or 15 kGy.
The basis of the dose setting methods described in this part of ISO 11137 (Methods 1 and 2) owe much to the
[19][20][21] [10][11]
ideas first propounded by Tallentire . Subsequently, standardized protocols were developed ,
which formed the basis of the dose setting methods detailed in the AAMI Recommended Practice for
[6][8]
Sterilization by Gamma Radiation .
Methods 1 and 2 and the associated sterilization dose audit procedures use data derived from the inactivation
of the microbial population in its natural state on product. The methods are based on a probability model for
the inactivation of microbial populations. The probability model, as applied to bioburden made up of a mixture
of various microbial species, assumes that each such species has its own unique D value. In the model, the
10
probability that an item will possess a surviving microorganism after exposure to a given dose of radiation is
defined in terms of the initial number of microorganisms on the item prior to irradiation and the D values of
10
the microorganisms. The methods involve performance of tests of sterility on product items that have received
doses of radiation lower than the sterilization dose. The outcome of these tests is used to predict the dose
needed to achieve a predetermined sterility assurance level (SAL).
Methods 1 and 2 can also be used to substantiate 25 kGy if, on performing a dose setting exercise, the
–6
derived sterilization dose for an SAL of 10 is less than or equal to 25 kGy. The basis of the method devised
[16]
specifically for substantiation of 25 kGy, Method VD , was put forward by Kowalski and Tallentire .
max
Subsequent evaluations involving computational techniques demonstrated that the underlying principles were
[15]
soundly based and field trials confirmed that Method VD is effective in substantiating 25 kGy for a wide
max
[18]
variety of medical devices manufactured and assembled in different ways .
A standardized procedure for the use of VD for substantiation of a sterilization dose of 25 kGy has been
max
published in the AAMI Technical Information Report Sterilization of health care products — Radiation
[7]
sterilization — Substantiation of 25 kGy as a sterilization dose — Method VD , a text on which the
max
method described herein is largely based. Method VD is founded on dose setting Method 1 and, as such, it
max
possesses the high level of conservativeness characteristic of Method 1. In a similar manner to the dose
setting methods, it involves performance of tests of sterility on product items that have received a dose of
radiation lower than the sterilization dose. The outcomes of these tests are used to substantiate that 25 kGy
–6
achieves an SAL of 10 .
To link the use of VD for the substantiation of a particular preselected sterilization dose, the numerical value
max
of the latter, expressed in kilograys, is included as a superscript to the VD symbol. Thus, for substantiation
max
25
of a sterilization dose of 25 kGy, the method is designated Method VD .
max
15 25
Method VD is based on the same principles as Method VD . The test procedure is similar to that of
max max
25 15
Method VD , but Method VD is limited to product with an average bioburden less than or equal to
max max
1,5. The outcomes of the associated tests of sterility are used to substantiate that 15 kGy achieve a sterility
–6
assurance level of 10 .
This part of ISO 11137 also describes methods that can be used to carry out sterilization dose audits in
accordance with ISO 11137-1:2006, Clause 12. Following establishment of the sterilization dose, sterilization
dose audits are performed routinely to confirm that the sterilization dose continues to achieve the desired SAL.
vi © ISO 2012 – All rights reserved
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SIST EN ISO 11137-2:2012
INTERNATIONAL STANDARD ISO 11137-2:2012(E)
Sterilization of health care products — Radiation —
Part 2:
Establishing the sterilization dose
1 Scope
This part of ISO 11137 specifies methods for determining the minimum dose needed to achieve a specified
requirement for sterility and methods to substantiate the use of 25 kGy or 15 kGy as the sterilization dose to
–6
achieve a sterility assurance level, SAL, of 10 . This part of ISO 11137 also specifies methods of sterilization
dose audit used to demonstrate the continued effectiveness of the sterilization dose.
This part of ISO 11137 defines product families for sterilization dose establishment and sterilization dose audit.
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 11137-1:2006, Sterilization of health care products — Radiation — Part 1: Requirements for the
development, validation and routine control of a sterilization process for medical devices
ISO 11737-1, Sterilization of medical devices — Microbiological methods — Part 1: Determination of a
population of microorganisms on products
ISO 11737-2, Sterilization of medical devices — Microbiological methods — Part 2: Tests of sterility performed
in the definition, validation and maintenance of a sterilization process
3 Terms, definitions and abbreviated terms
For the purposes of this document, the terms and definitions given in ISO 11137-1 and the following apply.
3.1 Terms and definitions
3.1.1
batch
defined quantity of product, intended or purported to be uniform in character and quality, which has been
produced during a defined cycle of manufacture
[ISO/TS 11139:2006, definition 2.1]
3.1.2
bioburden
population of viable microorganisms on or in product and/or sterile barrier system
[ISO/TS 11139:2006, definition 2.2]
© ISO 2012 – All rights reserved 1
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SIST EN ISO 11137-2:2012
ISO 11137-2:2012(E)
3.1.3
false positive
test result interpreted as growth arising from the product, or portions thereof, tested when either growth
resulted from extraneous microbial contamination or turbidity occurred from interaction between the product,
or portions thereof, and the test medium
3.1.4
fraction positive
quotient in which the number of positive tests of sterility is given by the numerator and the number of tests
performed is given by the denominator
3.1.5
incremental dose
dose within a series of doses applied to a number of product, or portions thereof, and used in a dose setting
method to obtain or confirm the sterilization dose
3.1.6
negative test of sterility
test result for which there is no detectable microbial growth from product, or portions thereof, subjected to a
test of sterility
3.1.7
packaging system
combination of the sterile barrier system and protective packaging
[ISO/TS 11139:2006, definition 2.28]
3.1.8
positive test of sterility
test result for which there is detectable microbial growth from product, or portions thereof, subjected to a test
of sterility
3.1.9
sample item portion
SIP
defined portion of a health care product that is tested
3.1.10
standard distribution of resistances
SDR
reference set of resistances of microorganisms and corresponding probabilities of occurrence
3.1.11
sterile barrier system
minimum package that prevents ingress of microorganisms and allows aseptic presentation of product at the
point of use
3.1.12
sterility assurance
...
EUROPEAN STANDARD
DRAFT
prEN ISO 11137-2
NORME EUROPÉENNE
EUROPÄISCHE NORM
May 2004
ICS
English version
Sterilization of health care products - Radiation - Part 2:
Establishing the sterilization dose
Stérilisation des produits de santé - Irradiation - Partie 2:
Etablissement de la dose de stérilisation
This draft European Standard is submitted to CEN members for parallel enquiry. It has been drawn up by the Technical Committee
CEN/TC 204.
If this draft becomes a European Standard, 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.
This draft European Standard was established by CEN 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 Management Centre has the same
status as the official versions.
CEN members are the national standards bodies of Austria, Belgium, Cyprus, Czech Republic, Denmark, Estonia, Finland, France,
Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Slovakia,
Slovenia, Spain, Sweden, Switzerland and United Kingdom.
Warning : This document is not a European Standard. It is distributed for review and comments. It is subject to change without notice and
shall not be referred to as a European Standard.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: rue de Stassart, 36 B-1050 Brussels
© 2004 CEN All rights of exploitation in any form and by any means reserved Ref. No. prEN ISO 11137-2:2004: E
worldwide for CEN national Members.
---------------------- Page: 1 ----------------------
prEN ISO 11137-2:2004 (E)
Foreword
This document (prEN ISO 11137-2:2004) 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 document is currently submitted to the parallel Enquiry.
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).
Endorsement notice
The text of ISO/DIS 11137-2:2004 has been approved by CEN as prEN ISO 11137-2:2004
without any modifications.
2
---------------------- Page: 2 ----------------------
DRAFT INTERNATIONAL STANDARD ISO/DIS 11137-2
ISO/TC 198 Secretariat: ANSI
Voting begins on: Voting terminates on:
2004-05-06 2004-10-06
INTERNATIONAL ORGANIZATION FOR STANDARDIZATION • МЕЖДУНАРОДНАЯ ОРГАНИЗАЦИЯ ПО СТАНДАРТИЗАЦИИ • ORGANISATION INTERNATIONALE DE NORMALISATION
Sterilization of health care products — Radiation —
Part 2:
Establishing the sterilization dose
Stérilisation des produits de santé — Irradiation —
Partie 2: Établissement de la dose de stérilisation
ICS 11.080.01
ISO/CEN PARALLEL ENQUIRY
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vote in ISO and formal vote in CEN.
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© International Organization for Standardization, 2004
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ISO/DIS 11137-2
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ii ISO 2004 – All rights reserved
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ISO/DIS 11137-2
Contents Page
1 Scope.1
2 Normative references.1
3 Terms and definitions .1
3.1 Terms.1
3.2 Definitions .3
4 Definition and maintenance of product families for dose setting, dose substantiation and
sterilization dose auditing .3
4.1 General .3
4.2 Defining product families .4
4.3 Designation of product to represent a product family for performance of a verification
dose experiment and a sterilization dose audit .4
4.3.1 Product to represent a product family .4
4.3.2 Master product.5
4.3.3 Equivalent product.5
4.3.4 Simulated product.5
4.4 Maintaining product families.6
4.4.1 Periodic review .6
4.4.2 Modification to product and/or manufacturing process .6
4.4.3 Records .6
4.5 Effect of failure of establishment of sterilization dose or of a sterilization dose audit on a
product family.6
5 Selection and testing of product for establishing and verifying the sterilization dose.6
5.1 Nature of product .6
5.2 Sample item portion (SIP).7
5.3 Manner of sampling.8
5.4 Microbiological testing .8
5.5 Irradiation .8
6 Methods of dose establishment.9
7 Method 1: Dose setting using bioburden information.9
7.1 Rationale .9
7.2 Product with an average bioburden equal to or greater than 1,0.10
7.2.1 Procedure for Method 1 for multiple batches.10
7.2.1.1 General.10
7.2.1.2 Stage 1: Select SAL and obtain product samples.10
7.2.1.3 Stage 2: Determine average bioburden.10
7.2.1.4 Stage 3: Obtain verification dose.11
7.2.1.5 Stage 4: Perform verification dose experiment .11
7.2.1.6 Stage 5: Establish sterilization dose .12
7.2.2 Procedure for Method 1 adapted for a single production batch .15
7.2.2.1 Rationale.15
7.2.2.2 General.15
7.2.2.3 Stage 1: Select SAL and obtain product samples.15
7.2.2.4 Stage 2: Determine average bioburden.15
7.2.2.5 Stage 3: Obtain verification dose.15
7.2.2.6 Stage 4: Perform verification dose experiment .15
7.2.2.7 Stage 5: Establish sterilization dose .16
7.3 Product with an average bioburden in the range 0,1 to 0,9 inclusive, for multiple or single
batches .16
© ISO 2004 – All rights reserved iii
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ISO/DIS 11137-2
8 Method 2: Dose setting using fraction positive information from incremental dosing to
determine an extrapolation factor. 17
8.1 Rationale. 17
8.2 Procedure for Method 2A. 17
8.2.1 General. 17
8.2.2 Stage 1: Select SAL and obtain product samples. 17
8.2.3 Stage 2: Perform incremental dose experiment. 18
8.2.3.1 General. 18
8.2.3.2 A and FFP. 18
8.2.3.3 D* . 19
8.2.3.4 CD* batch . 19
8.2.4 Stage 3: Perform verification dose experiment. 19
8.2.5 Stage 4: Establish sterilization dose . 20
8.3 Procedure for Method 2B. 20
8.3.1 General. 20
8.3.2 Stage 1: Select SAL and obtain product samples. 21
8.3.3 Stage 2: Perform incremental dose experiment. 21
8.3.3.1 General. 21
8.3.3.2 A and FFP. 21
8.3.3.3 D* . 22
8.3.3.4 CD* batch . 22
8.3.4 Stage 3: Perform verification dose experiment. 23
8.3.5 Stage 4: Establish sterilization dose . 23
9 Method VD . 24
max
9.1 Rationale. 24
9.2 Product with an average bioburden within the range 0,1 to 1000 inclusive. 24
25
9.2.1 Procedure for Method VD for multiple production batches . 24
max
9.2.1.1 General. 24
9.2.1.2 Stage 1: Obtain product samples. 25
9.2.1.3 Stage 2: Determine average bioburden . 25
25
9.2.1.4 Stage 3: Obtain VD . 25
max
9.2.1.5 Stage 4: Perform verification dose experiment . 27
9.2.1.6 Stage 5: Interpretation of results. 27
9.2.2 Confirmatory verification dose experiment . 27
9.2.2.1 General. 27
9.2.2.2 Stage 1: Obtain product samples. 27
9.2.2.3 Stage 2: Perform confirmatory verification dose experiment . 27
9.2.2.4 Stage 3: Interpretation of results. 28
25
9.2.3 Procedure for Method VD for a single production batch . 28
max
9.2.3.1 Rationale . 28
9.2.3.2 General. 28
9.2.3.3 Stage 1: Obtain product samples. 28
9.2.3.4 Stage 2: Determine average bioburden . 28
25
9.2.3.5 Stage 3: Obtain VD . 28
max
9.2.3.6 Stage 4: Perform verification dose experiment . 29
9.2.3.7 Stage 5: Interpretation of results. 29
9.3 Product with an average bioburden within the range 0,1 to 1,5 inclusive. 29
15
9.3.1 Procedure for Method VD for multiple production batches . 29
max
9.3.1.1 General. 29
9.3.1.2 Stage 1: Obtain product samples. 29
9.3.1.3 Stage 2: Determine average bioburden . 30
15
9.3.1.4 Stage 3: Obtain VD . 30
max
9.3.1.5 Stage 4: Perform verification dose experiment . 30
9.3.1.6 Stage 5: Interpretation of results. 31
9.3.2 Confirmatory verification dose experiment . 31
9.3.2.1 General. 31
iv © ISO 2004 – All rights reserved
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ISO/DIS 11137-2
9.3.2.2 Stage 1: Obtain product samples.31
9.3.2.3 Stage 2: Perform confirmatory verification dose experiment.31
9.3.2.4 Stage 3: Interpretation of results .31
15
9.3.3 Procedure for Method VD for a single production batch.32
max
9.3.3.1 Rationale.32
9.3.3.2 General.32
9.3.3.3 Stage 1: Obtain product samples.32
9.3.3.4 Stage 2: Determine average bioburden.32
15
9.3.3.5 Stage 3: Obtain VD .32
max
9.3.3.6 Stage 4: Perform verification dose experiment .32
9.3.3.7 Stage 5: Interpretation of results .32
10 Auditing the sterilization dose .33
10.1 Purpose and frequency.33
10.2 Procedure for auditing a sterilization dose established using Method 1 or Method 2 .33
10.2.1 General .33
10.2.2 Stage 1: Obtain product samples .33
10.2.3 Stage 2: Determine average bioburden.33
10.2.4 Stage 3: Perform verification dose experiment.33
10.2.5 Stage 4: Interpretation of results .34
10.2.6 Augmentation of a sterilization dose established using Method 1, Method 2A, or Method
2B .34
10.2.6.1 General.34
10.2.6.2 Stage 1: Analyze data from the failed dose audit.34
10.2.6.3 Stage 2: Determine extrapolation factor.35
-2
10.2.6.4 Stage 3: Calculate adjusted dose (the dose to achieve a 10 SAL) .35
10.2.6.5 Stage 4: Calculate augmented sterilization dose .35
10.3 Procedure for auditing a sterilization dose substantiated using VD .35
max
10.3.1 General .35
10.3.2 Stage 1: Obtain product samples .36
10.3.3 Stage 2: Determine average bioburden.36
10.3.4 Stage 3: Perform verification dose experiment.36
10.3.5 Stage 4: Interpretation of results .36
10.3.6 Confirmatory sterilization dose audit.37
10.3.6.1 General.37
10.3.6.2 Stage 1: Obtain product samples.37
10.3.6.3 Stage 2: Perform confirmatory verification dose experiment.37
10.3.6.4 Stage 3: Interpretation of results .37
25 15
10.3.7 Augmentation of a sterilization dose substantiated using Method VD or VD .37
max max
25
10.3.7.1 VD .37
max
15
10.3.7.2 VD .38
max
11 Worked examples.39
11.1 Worked examples for Method 1 .39
11.2 Worked examples for Method 2 .41
11.2.1 General .41
11.2.2 Worked example for Method 2A (SIP = 1,0) .41
11.2.2.1 Stage 1: Select SAL and obtain product samples.41
11.2.2.2 Stage 2: Perform incremental dose experiment .42
11.2.2.3 Stage 3: Perform verification dose experiment .43
11.2.2.4 Stage 4: Establish sterilization dose .44
11.2.3 Worked example for Method 2A (SIP < 1,0) .44
11.2.3.1 Stage 1: Select SAL and obtain product samples.44
11.2.3.2 Stage 2: Perform incremental dose experiment .45
11.2.3.3 Stage 3: Perform verification dose experiment .46
11.2.3.4 Stage 4: Establish sterilization dose .47
11.2.4 Worked example for Method 2B.47
11.2.4.1 Stage 1: Select SAL and obtain product samples.47
11.2.4.2 Stage 2: Perform incremental dose experiment .48
11.2.4.3 Stage 3: Perform verification dose experiment .49
11.2.4.4 Stage 4: Establish sterilization dose .50
© ISO 2004 – All rights reserved v
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