SIST EN ISO 11137-2:2013
(Main)Sterilization of health care products - Radiation - Part 2: Establishing the sterilization dose (ISO 11137-2:2013)
Sterilization of health care products - Radiation - Part 2: Establishing the sterilization dose (ISO 11137-2:2013)
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 11137-2:2013)
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 11137-2:2013)
Sterilizacija izdelkov za zdravstveno nego - Sevanje - 2. del: Določanje odmerka sterilizacije (ISO 11137-2:2013)
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
Related Packages
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 11137-2:2013
01-september-2013
1DGRPHãþD
SIST EN ISO 11137-2:2012
6WHULOL]DFLMDL]GHONRY]D]GUDYVWYHQRQHJR6HYDQMHGHO 'RORþDQMHRGPHUND
VWHULOL]DFLMH ,62
Sterilization of health care products - Radiation - Part 2: Establishing the sterilization
dose (ISO 11137-2:2013)
Sterilisation von Produkten für die Gesundheitsfürsorge - Strahlen - Teil 2: Festlegung
der Sterilisationsdosis (ISO 11137-2:2013)
Stérilisation des produits de santé - Irradiation - Partie 2: Établissement de la dose
stérilisante (ISO 11137-2:2013)
Ta slovenski standard je istoveten z: EN ISO 11137-2:2013
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
SIST EN ISO 11137-2:2013 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
---------------------- Page: 1 ----------------------
SIST EN ISO 11137-2:2013
---------------------- Page: 2 ----------------------
SIST EN ISO 11137-2:2013
EUROPEAN STANDARD
EN ISO 11137-2
NORME EUROPÉENNE
EUROPÄISCHE NORM
June 2013
ICS 11.080.01 Supersedes EN ISO 11137-2:2012
English Version
Sterilization of health care products - Radiation - Part 2:
Establishing the sterilization dose (ISO 11137-2:2013)
Stérilisation des produits de santé - Irradiation - Partie 2: Sterilisation von Produkten für die Gesundheitsfürsorge -
Établissement de la dose stérilisante (ISO 11137-2:2013) Strahlen - Teil 2: Festlegung der Sterilisationsdosis (ISO
11137-2:2013)
This European Standard was approved by CEN on 25 May 2013.
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
Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2013 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 11137-2:2013: E
worldwide for CEN national Members.
---------------------- Page: 3 ----------------------
SIST EN ISO 11137-2:2013
EN ISO 11137-2:2013 (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 11137-2:2013
EN ISO 11137-2:2013 (E)
Foreword
This document (EN ISO 11137-2:2013) 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 December 2013, and conflicting national standards shall be withdrawn
at the latest by December 2013.
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 11137-2:2012.
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 Annex ZA, B and C, 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, 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 11137-2:2013 has been approved by CEN as EN ISO 11137-2:2013 without any modification.
3
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SIST EN ISO 11137-2:2013
EN ISO 11137-2:2013 (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 European 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 11137-2:2013
EN ISO 11137-2:2013 (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 European 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
---------------------- Page: 7 ----------------------
SIST EN ISO 11137-2:2013
EN ISO 11137-2:2013 (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 European 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 11137-2:2013
INTERNATIONAL ISO
STANDARD 11137-2
Third edition
2013-06-01
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 11137-2:2013(E)
©
ISO 2013
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SIST EN ISO 11137-2:2013
ISO 11137-2:2013(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2013
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form
or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior
written permission. Permission can be requested 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 2013 – All rights reserved
---------------------- Page: 10 ----------------------
SIST EN ISO 11137-2:2013
ISO 11137-2:2013(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 . 4
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 . 6
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 . 9
6 Methods of dose establishment . 9
7 Method 1: dose setting using bioburden information .10
7.1 Rationale.10
7.2 Procedure for Method 1 for product with an average bioburden greater than or equal
to 1,0 for multiple production batches .11
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 .37
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
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 46
Method VD .
max
10.4 Failure of a sterilization dose audit .52
11 Worked examples .52
© ISO 2013 – All rights reserved iii
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SIST EN ISO 11137-2:2013
ISO 11137-2:2013(E)
11.1 Worked examples for Method 1 .52
11.2 Worked examples for Method 2 .54
11.3 Worked examples for Method VD .
max 62
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 .64
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 .64
11.6 Worked example of a sterilization dose audit for a sterilization dose substantiated using
25 65
Method VD .
max
Bibliography .67
iv © ISO 2013 – All rights reserved
---------------------- Page: 12 ----------------------
SIST EN ISO 11137-2:2013
ISO 11137-2:2013(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 third edition cancels and replaces the second edition (ISO 11137-2:2012), of which it constitutes a
minor revision with the following changes:
— addition of the word “and” in 9.1, second paragraph, third sentence;
— addition of the word “not” in 10.3.4.1, third paragraph;
— correction of the language used to describe requirements for interpretation of results during a verification
dose experiment in the second paragraph in 7.2.6.2, 7.3.7.2, 9.2.6.3, 9.3.7.3, 9.4.6.3, and 9.5.7.3.
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 2013 – All rights reserved v
---------------------- Page: 13 ----------------------
SIST EN ISO 11137-2:2013
ISO 11137-2:2013(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
[19][20][21]
much to the ideas first propounded by Tallentire . Subsequently, standardized protocols
[10][11]
were developed , which formed the basis of the dose setting methods detailed in the AAMI
[6][8]
Recommended Practice for 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 probability that an item will possess a surviving microorganism after
10
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 the microorganisms. The methods involve performance
10
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
[15]
were soundly based and field trials confirmed that Method VD is effective in substantiating 25 kGy
max
[18]
for a wide 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
max
has been published in the AAMI Technical Information Report Sterilization of health care products —
[7]
Radiation sterilization — Substantiation of 25 kGy as a sterilization dose — Method VD , a text on
max
which the method described herein is largely based. Method VD is founded on dose setting Method 1
max
and, as such, it 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
−6
to substantiate that 25 kGy achieves an SAL of 10 .
To link the use of VD for the substantiation of a particular preselected sterilization dose, the numerical
max
value of the latter, expressed in kilograys, is included as a superscript to the VD symbol. Thus, for
max
25
substantiation 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
max max
25 15
that of Method VD , but Method VD is limited to product with an average bioburden less than
max max
or equal to 1,5. The outcomes of the associated tests of sterility are used to substantiate that 15 kGy
−6
achieves a sterility 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 2013 – All rights reserved
---------------------- Page: 14 ----------------------
SIST EN ISO 11137-2:2013
INTERNATIONAL STANDARD ISO 11137-2:2013(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
−6
dose to 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 documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. 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: Deter
...
SLOVENSKI STANDARD
kSIST FprEN ISO 11137-2:2013
01-april-2013
6WHULOL]DFLMDL]GHONRY]D]GUDYVWYHQRQHJR6HYDQMHGHO 'RORþDQMHRGPHUND
VWHULOL]DFLMH ,62)',6
Sterilization of health care products - Radiation - Part 2: Establishing the sterilization
dose (ISO/FDIS 11137-2:2013)
Sterilisation von Produkten für die Gesundheitsfürsorge - Strahlen - Teil 2: Festlegung
der Sterilisationsdosis (ISO/FDIS 11137-2:2013)
Stérilisation des produits de santé - Irradiation - Partie 2: Établissement de la dose
stérilisante (ISO/FDIS 11137-2:2013)
Ta slovenski standard je istoveten z: FprEN ISO 11137-2
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
kSIST FprEN ISO 11137-2:2013 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
---------------------- Page: 1 ----------------------
kSIST FprEN ISO 11137-2:2013
---------------------- Page: 2 ----------------------
kSIST FprEN ISO 11137-2:2013
EUROPEAN STANDARD
FINAL DRAFT
FprEN ISO 11137-2
NORME EUROPÉENNE
EUROPÄISCHE NORM
January 2013
ICS 11.080.01 Will supersede EN ISO 11137-2:2012
English Version
Sterilization of health care products - Radiation - Part 2:
Establishing the sterilization dose (ISO/FDIS 11137-2:2013)
Stérilisation des produits de santé - Irradiation - Partie 2: Sterilisation von Produkten für die Gesundheitsfürsorge -
Établissement de la dose stérilisante (ISO/FDIS 11137- Strahlen - Teil 2: Festlegung der Sterilisationsdosis
2:2013) (ISO/FDIS 11137-2:2013)
This draft European Standard is submitted to CEN members for unique acceptance procedure. 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 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.
Recipients of this draft are invited to submit, with their comments, notification of any relevant patent rights of which they are aware and to
provide supporting documentation.
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: Avenue Marnix 17, B-1000 Brussels
© 2013 CEN All rights of exploitation in any form and by any means reserved Ref. No. FprEN ISO 11137-2:2013: E
worldwide for CEN national Members.
---------------------- Page: 3 ----------------------
kSIST FprEN ISO 11137-2:2013
FprEN ISO 11137-2:2013 (E)
Contents
Page
Foreword . 3
2
---------------------- Page: 4 ----------------------
kSIST FprEN ISO 11137-2:2013
FprEN ISO 11137-2:2013 (E)
Foreword
This document (FprEN ISO 11137-2:2013) 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 Unique Acceptance Procedure.
This document will supersede EN ISO 11137-2:2012.
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/FDIS 11137-2:2013 has been approved by CEN as FprEN ISO 11137-2:2013 without any
modification.
3
---------------------- Page: 5 ----------------------
kSIST FprEN ISO 11137-2:2013
---------------------- Page: 6 ----------------------
kSIST FprEN ISO 11137-2:2013
FINAL
INTERNATIONAL ISO/FDIS
DRAFT
STANDARD 11137-2
ISO/TC 198
Sterilization of health care
Secretariat: ANSI
products — Radiation —
Voting begins on:
2013-01-24
Part 2:
Voting terminates on:
Establishing the sterilization dose
2013-03-24
Stérilisation des produits de santé — Irradiation —
Partie 2: Établissement de la dose stérilisante
Please see the administrative notes on page iii
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OF ANY RELEVANT PATENT RIGHTS OF WHICH
THEY ARE AWARE AND TO PROVIDE SUPPOR TING
DOCUMENTATION.
IN ADDITION TO THEIR EVALUATION AS
Reference number
BEING ACCEPTABLE FOR INDUSTRIAL, TECHNO-
ISO/FDIS 11137-2:2013(E)
LOGICAL, COMMERCIAL AND USER PURPOSES,
DRAFT INTERNATIONAL STANDARDS MAY ON
OCCASION HAVE TO BE CONSIDERED IN THE
LIGHT OF THEIR POTENTIAL TO BECOME STAN-
DARDS TO WHICH REFERENCE MAY BE MADE IN
©
NATIONAL REGULATIONS. ISO 2013
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kSIST FprEN ISO 11137-2:2013
ISO/FDIS 11137-2:2013(E)
Copyright notice
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ii © ISO 2013 – All rights reserved
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kSIST FprEN ISO 11137-2:2013
ISO/FDIS 11137-2:2013(E)
ISO/CEN PARALLEL PROCESSING
This final draft has been developed within the International Organization for Standardization (ISO), and pro-
cessed under the ISO-lead mode of collaboration as defined in the Vienna Agreement. The final draft was
established on the basis of comments received during a parallel enquiry on the draft.
This final draft is hereby submitted to the ISO member bodies and to the CEN member bodies for a parallel
two-month approval vote in ISO and formal vote in CEN.
Positive votes shall not be accompanied by comments.
Negative votes shall be accompanied by the relevant technical reasons.
© ISO 2013 – All rights reserved iii
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kSIST FprEN ISO 11137-2:2013
ISO/FDIS 11137-2:2013(E)
Contents Page
Foreword .vi
Introduction .vii
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 . 4
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 . 6
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 . 9
6 Methods of dose establishment . 9
7 Method 1: dose setting using bioburden information .10
7.1 Rationale.10
7.2 Procedure for Method 1 for product with an average bioburden greater than or equal
to 1,0 for multiple production batches .11
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 .37
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
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 46
Method VD .
max
10.4 Failure of a sterilization dose audit .52
11 Worked examples .52
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kSIST FprEN ISO 11137-2:2013
ISO/FDIS 11137-2:2013(E)
11.1 Worked examples for Method 1 .52
11.2 Worked examples for Method 2 .54
11.3 Worked examples for Method VD .
max 62
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 .64
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 .64
11.6 Worked example of a sterilization dose audit for a sterilization dose substantiated using
25 65
Method VD .
max
Annex ZA (informative) Relationship between this International Standard and the Essential
Requirements of EU Directive 90/385/EEC on active implantable medical devices .67
Annex ZB (informative) Relationship between this International Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices .68
Annex ZC (informative) Relationship between this International Standard and the Essential
Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devices .69
Bibliography .70
© ISO 2013 – All rights reserved v
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kSIST FprEN ISO 11137-2:2013
ISO/FDIS 11137-2:2013(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 third edition cancels and replaces the second edition (ISO 11137-2:2012), of which it constitutes a
minor revision with the following changes:
— addition of the word “and” in 9.1, second paragraph, third sentence;
— addition of the word “not” in 10.3.4.1, third paragraph;
— correction of the language used to describe requirements for interpretation of results during a verification
dose experiment in the second paragraph in 7.2.6.2, 7.3.7.2, 9.2.6.3, 9.3.7.3, 9.4.6.3, and 9.5.7.3.
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
vi © ISO 2013 – All rights reserved
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kSIST FprEN ISO 11137-2:2013
ISO/FDIS 11137-2:2013(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
[19][20][21]
much to the ideas first propounded by Tallentire . Subsequently, standardized protocols
[10][11]
were developed , which formed the basis of the dose setting methods detailed in the AAMI
[6][8]
Recommended Practice for 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 probability that an item will possess a surviving microorganism after
10
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 the microorganisms. The methods involve performance
10
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
[15]
were soundly based and field trials confirmed that Method VD is effective in substantiating 25 kGy
max
[18]
for a wide 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
max
has been published in the AAMI Technical Information Report Sterilization of health care products —
[7]
Radiation sterilization — Substantiation of 25 kGy as a sterilization dose — Method VD , a text on
max
which the method described herein is largely based. Method VD is founded on dose setting Method 1
max
and, as such, it 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
−6
to substantiate that 25 kGy achieves an SAL of 10 .
To link the use of VD for the substantiation of a particular preselected sterilization dose, the numerical
max
value of the latter, expressed in kilograys, is included as a superscript to the VD symbol. Thus, for
max
25
substantiation 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
max max
25 15
that of Method VD , but Method VD is limited to product with an average bioburden less than
max max
or equal to 1,5. The outcomes of the associated tests of sterility are used to substantiate that 15 kGy
−6
achieves a sterility 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.
© ISO 2013 – All rights reserved vii
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kSIST FprEN ISO 11137-2:2013
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kSIST FprEN ISO 11137-2:2013
FINAL DRAFT INTERNATIONAL STANDARD ISO/FDIS 11137-2:2013(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
−6
dose to 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 documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. 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, d efinitions , 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 definiti ons
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 2013 – All rights reserved 1
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kSIST FprEN ISO 11137-2:2013
ISO/FDIS 11137-2:2013(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 level
SAL
probability of a single viable microorganism occurring on an item after sterilization
−6 −3
Note 1 to entry: The term SAL takes a quantitative value, generally 10 or 10 . When applying this quantitative
−6
value to assurance of sterility, an SAL of 10 has a lower value but provides a greater assurance of sterility than
−3
an SAL of 10 .
[ISO/TS 11139:2006, definition 2.46]
3.1.13
sterilization dose audit
exercise undertaken to confirm the appropriateness of an established sterilization dose
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kSIST FprEN ISO 11137-2:2013
ISO/FDIS 11137-2:2013(E)
3.1.14
test of sterility
technical operation performed as part of development, validation, or requalification to determine the
presence or absence of viable microorganisms on product or portions thereof
[ISO/TS 11139:2006, definition 2.54]
3.1.15
ver i f ic at ion dos e
−2
dose of radiation predicted to give a predetermined SAL greater than or equal to 10 used in establishing
the sterilization dose
3.2 Abbreviated terms
3.2.1
A
dose to adjust the median ffp dose downwards to the FFP dose
3.2.2
CD*
number of positive tests of sterility obtained from tests performed individuall
...
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