SIST EN ISO 11137-2:2012

SLOVENSKI STANDARD
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
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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.

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

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.
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.
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.
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.
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
ISO 11137-2:2012(E)
© 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
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Published in Switzerland
ii © ISO 2012 – All rights reserved

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
9.2  Procedure for Method VD for multiple production batches . 29
max
9.3  Procedure for Method VD for a single production batch . 34
max
9.4  Procedure for Method VD for multiple production batches . 36
max
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 11137-2:2012(E)
10.2  Procedure for auditing a sterilization dose established using Method 1, Method 2A or
Method 2B .43
10.3  Procedure for auditing a sterilization dose substantiated using Method VD or
max
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
Method VD .67
max
Bibliography .69

iv © ISO 2012 – All rights reserved

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 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
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
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
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

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 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 level
SAL
probability of a single viable microorganism occurring on an item after sterilization
–6 –3
NOTE The term SAL takes a quantitative value, generally 10 or 10 . When applying this quantitative value to
–6 –3
assurance of sterility, an SAL of 10 has a lower value but provides a greater assurance of sterility than an SAL of 10 .
[ISO/TS 11139:2006, definition 2.46]
2 © ISO 2012 – All rights reserved

ISO 11137-2:2012(E)
3.1.13
sterilization dose audit
exercise undertaken to confirm the appropriateness of an established sterilization dose
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
verification dose
–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 individually on 100 product items irradiated
in a Method 2 verification dose experiment
3.2.3
d *
dose derived from an incremental dose experiment performed on product items drawn from a given production
batch
3.2.4
D*
2
initial estimate of the dose to provide an SAL of 10 for the test items
NOTE Generally, it is the median of the three d * values derived for a given product.
3.2.5
D**
2
final estimate of the dose to provide an SAL of 10 for the test items, which is used in the calculation of the
sterilization dose
3.2.6
DD*
highest dose delivered in a Method 2 verification dose experiment
3.2.7
DS
estimate of the D value of microorganisms present on product after exposure to DD*
3.2.8
D value
D value
time or dose required to achieve inactivation of 90 % of a population of the test microorganism under stated
conditions
[ISO/TS 11139:2006, definition 2.11]
NOTE For the purposes of this part of ISO 11137, D applies to the radiation dose only and not to time.
ISO 11137-2:2012(E)
3.2.9
first fraction positive dose
ffp
lowest dose of an incremental dose series, applied to product items drawn from a given production batch, at
which at least one of the associated 20 tests of sterility is negative
3.2.10
First Fraction Positive dose
FFP
dose at which 19 positives out of the 20 tests of sterility are expected to occur, calculated by subtracting A
from the median of three ffp doses
3.2.11
First No Positive dose
FNP
–2
estimate of the dose to provide an SAL of 10 for the test items, that is used in the calculation of DS
3.2.12
VD
max
–6
maximal verification dose for a given bioburden, consistent with the attainment of an SAL of 10 at
a specified sterilization dose of 15 kGy
3.2.13
VD
max
–6
maximal verification dose for a given bioburden, consistent with the attainment of an SAL of 10 at
a specified sterilization dose of 25 kGy
4 Definition and maintenance of product families for dose setting, dose
substantiation and sterilization dose auditing
4.1 General
The establishment of a sterilization dose and the carrying out of sterilization dose audits are activities that are
part of process definition (see Clause 8 of ISO 11137-1:2006) and maintaining process effectiveness
(see Clause 12 of ISO 11137-1:2006). For these activities, product may be grouped into families; definition of
product families is based principally on the numbers and types of microorganisms present on or in product
(the bioburden). The type of microorganism is indicative of its resistance to radiation. Variables such as
density and product configuration within its packaging system are not considered in the establishment of these
product families because they are not factors that influence bioburden.
In using product families for establishing the sterilization dose and for carrying out sterilization dose audits, it
is important to be aware of risks such as reduction in the ability to detect an inadvertent change within the
manufacturing process that influences the effectiveness of sterilization. Furthermore, the use of a single
product to represent the product family might not detect changes that occur in other members of the product
family. The risk associated with a reduction in ability to detect changes in other members of the product family
should be evaluated and a plan for maintaining product families developed and implemented before
proceeding.
NOTE See ISO 14971 for guidance related to risk management.
4 © ISO 2012 – All rights reserved

ISO 11137-2:2012(E)
4.2 Defining product families
4.2.1 The criteria for defining a product family shall be documented. Product shall be assessed against
these criteria and the similarities between potential product family members considered. Consideration shall
include all product-related variables that affect bioburden, including, but not limited to:
a) nature and sources of raw materials, including the effect, if any, of raw materials that might be sourced
from more than one location;
b) components;
c) product design and size;
d) manufacturing processes;
e) manufacturing equipment;
f) manufacturing environment;
g) manufacturing location.
The outcome of the assessment and considerations shall be recorded (see ISO 11137-1:2006, 4.1.2).
4.2.2 Product shall only be included in a product family if it is demonstrated that the product-related
variables (see 4.2.1) are similar and under control.
4.2.3 To include product within a product family, it shall be demonstrated that bioburden comprises similar
numbers and types of microorganisms.
4.2.4 Inclusion of product from more than one manufacturing location in a product family shall be
specifically justified and recorded (see ISO 11137-1:2006, 4.1.2). Consideration shall be given to the effect on
bioburden of:
a) geographic and/or climatic differences between locations;
b) any differences in the control of the manufacturing processes or environment;
c) sources of raw materials and processing adjuvants (e.g. water).
4.3 Designation of product to represent a product family for performance of a verification
dose experiment or sterilization dose audit
4.3.1 Product to represent a product family
4.3.1.1 The number and types of microorganisms on or in product shall be used as the basis for selecting
product to represent a product family.
4.3.1.2 A product family shall be represented by:
a) the master product (see 4.3.2), or
b) an equivalent product (see 4.3.3), or
c) a simulated product (see 4.3.4).
ISO 11137-2:2012(E)
4.3.1.3 A formal, documented assessment shall be undertaken to decide which of the three potential
representative products in 4.3.1.2 is appropriate. In this assessment, consideration shall be given to the
following:
a) number of microorganisms comprising the bioburden;
b) types of microorganisms comprising the bioburden;
c) environment in which the microorganisms occur;
d) size of product;
e) number of components;
f) complexity of product;
g) degree of automation during manufacture;
h) manufacturing environment.
4.3.2 Master product
A member of a product family shall only be considered a master product if assessment (see 4.3.1.3) indicates
that the member presents a challenge that is greater than that of all other product family members. In some
situations, there can be several products within the product family, each of which could be considered as the
master product. In such circumstances, any one of these products may be selected as the master product to
represent the family, either a) at random, or b) according to a documented procedure to include the different
products that could be considered as master products.
4.3.3 Equivalent product
A group of product shall only be considered equivalent if assessment (see 4.3.1.3) indicates that group
members require the same sterilization dose. Selection of the equivalent product to represent the family shall
be either a) at random, or b) according to a documented procedure to include different members of the
product family. The manufacturing volume and availability of product should be considered in the selection of
the equivalent product to represent the product family.
4.3.4 Simulated product
A simulated product shall only represent a product family if it constitutes an equivalent or greater challenge to
the sterilization process than that provided by members of the product family. Simulated product shall be
packaged in a manner and with materials used for the actual product.
NOTE A simulated product is not intended for clinical use; it is fabricated solely for the establishment or maintenance
of the sterilization dose.
A simulated product might be:
a) one which is similar to the actual product in terms of materials and size, and subjected to similar
manufacturing processes, e.g. a piece of the material used for implants that goes through the entire
manufacturing process, or
b) a combination of components from product within the product family that would not typically be combined
for use, e.g. a tubing set containing multiple filters, clamps and stopcocks that are components of other
products within the product family.
6 © ISO 2012 – All rights reserved

ISO 11137-2:2012(E)
4.4 Maintaining product families
4.4.1 Periodic review
Review shall be performed at a specified frequency to ensure that product families and product used to
represent each product family remain valid. Responsibility for reviews of product and/or processes that might
affect membership of product families shall be allocated to competent personnel. Such a review shall be
performed at least annually. The outcome of the review shall be recorded in accordance with
ISO 11137-1:2006, 4.1.2.
4.4.2 Modification to product and/or manufacturing process
Modifications to product, such as raw materials (nature and source), components or product design (including
size), and/or modifications to the manufacturing process, such as equipment, environment or location, shall be
assessed through a formal, documented change control system. Such modifications can alter the basis on
which the product family was defined or the basis on which the selection of product to represent the product
family was made. Significant changes can require definition of a new product family or the selection of a
different representative product.
4.4.3 Records
Records of product families shall be retained (see ISO 11137-1:2006, 4.1.2).
4.5 Effect of failure of establishment of sterilization dose or of a sterilization dose audit on
a product family
In the event of failure during establishment of the sterilization dose or performance of the sterilization dose
audit for a product family, all members of that family shall be considered to be affected. Subsequent actions
shall apply to all product comprising the product family.
5 Selection and testing of product for establishing the sterilization dose
5.1 Nature of product
5.1.1 Product for sterilization can consist of:
a) an individual health care product in its packaging system;
b) a set of components presented in a packaging system, which are assembled at the point of use to form
the health care product, together with accessories required to use the assembled product;
c) a number of identical health care products in their packaging system;
d) a kit comprising a variety of procedure-related health care products.
Product items for the performance of sterilization dose establishment shall be taken in accordance with
Table 1.
ISO 11137-2:2012(E)
Table 1 — Nature of product items for establishing the sterilization dose
Item for bioburden estimation,
Product type verification and/or Rationale
incremental dose experiment
Individual health care product in its Each health care product is used
Individual health care product
packaging system independently in clinical practice
Components are assembled as a
Set of components in a packaging Combination of all components of the
product and used together in clinical
system product
practice
Each health care product is used
independently in clinical practice; the
SAL of an individual health care
Number of identical health care Single health care product taken from
product within the packaging system
products in their packaging system the packaging system
meets the selected SAL, although the
overall SAL associated with the
packaging system might be higher
Kit of procedure-related health care Each type of health care product Each health care product is used
a
products comprising the kit independently in clinical practice
NOTE 1 See 5.2 for guidance on the use of SIP for product characterized in 5.1.1 b).
NOTE 2 See Clause 4 for the use of product families for product characterized in 5.1.1 d).
a
In dose establishment, the sterilization dose is chosen based on the health care product requiring the highest sterilization dose.
5.1.2 If the product has a claim of sterility for part of the product, the sterilization dose can be established
on the basis of that part only.
EXAMPLE If the product has a label claim of sterility for the fluid path only, the sterilization dose can be established
based on bioburden determinations and outcomes of tests of sterility performed on the fluid path.
5.2 Sample item portion (SIP)
5.2.1 For product with an average bioburden greater than or equal to 1,0, whenever practicable, an entire
product (SIP equal to 1,0) should be used for testing in accordance with Table 1. When the use of an entire
product is not practicable, a selected portion of product (SIP) may be substituted. The SIP should be as large
a portion of the item as practicable and should be of a size that can be handled during testing.
5.2.2 For a product with an average bioburden less than or equal to 0,9, an entire product (SIP equal to 1,0)
shall be used for testing in accordance with Table 1.
5.2.3 If the bioburden is evenly distributed on and/or in the item, the SIP may be selected from any portion
of the item. If the bioburden is not evenly distributed, the SIP shall consist of either a) portions of product
selected at random that proportionally represent each o
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