EN ISO 11137-2:2015

SLOVENSKI STANDARD
01-september-2015
1DGRPHãþD
SIST EN ISO 11137-2:2013
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
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 11137-2:2015
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EUROPEAN STANDARD
EN ISO 11137-2
NORME EUROPÉENNE
EUROPÄISCHE NORM
June 2015
ICS 11.080.01 Supersedes EN ISO 11137-2:2013
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 20 May 2015.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European
Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such national
standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN member.

This European Standard exists in three official versions (English, French, German). A version in any other language made by translation
under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management Centre has the same
status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and United
Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2015 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 11137-2:2015 E
worldwide for CEN national Members.

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

Foreword
The text of ISO 11137-2:2013 has been prepared by Technical Committee ISO/TC 198 “Sterilization of health
care products” of the International Organization for Standardization (ISO) and has been taken over as EN
ISO 11137-2:2015 by Technical Committee CEN/TC 204 “Sterilization of medical devices” the secretariat of
which is held by BSI.
This European Standard shall be given the status of a national standard, either by publication of an identical
text or by endorsement, at the latest by December 2015, and conflicting national standards shall be withdrawn
at the latest by December 2015.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 11137-2:2013.
This document has been prepared under a mandate given to CEN by the European Commission and the
European Free Trade Association, and supports essential requirements of EU Directives.
For relationship with EU Directives, see informative Annexes ZA, ZB and ZC, which are integral parts of this
document.
The following referenced documents are indispensable for the application of this document. For undated
references, the edition of the referenced document (including any amendments) listed below applies. For
dated references, only the edition cited applies. However, for any use of this standard within the meaning of
Annex ZA, ZB or ZC, the user should always check that any referenced document has not been superseded
and that its relevant contents can still be considered the generally acknowledged state-of-art.
When an IEC or ISO standard is referred to in the ISO standard text, this should be understood as a
normative reference to the corresponding EN standard, if available, and otherwise to the dated version of the
ISO or IEC standard as listed below.
NOTE The way in which these referenced documents are cited in normative requirements determines the extent (in
whole or in part) to which they apply.
Table — Correlation between normative references and dated EN and ISO standards
Normative references Equivalent dated standard
as listed in Clause 2 of the ISO
EN ISO
standard
ISO 11137 EN ISO 11137-1:2006/A1:2013 ISO 11137-1:2006/A1:2013
ISO 11737-1 EN ISO 11737-1:2006 + AC:2009 ISO 11737-1:2006 + Cor 1:2007
ISO 11737-2 EN ISO 11737-2:2009 ISO 11737-2:2009
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 11137-2:2015 without any modification.
Annex ZA
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on active implantable
medical devices
This European Standard has been prepared under a mandate given to CEN/CENELEC by the European
Commission and the European Free Trade Association to provide a means of conforming to Essential
Requirements of the New Approach Directive 90/385/EEC on active implantable medical devices.
Once this standard is cited in the Official Journal of the European Union under that Directive and has been
implemented as a national standard in at least one Member State, compliance with the normative clauses of
this standard given in Table ZA.1 confers, within the limits of the scope of this standard, a presumption of
conformity with the corresponding Essential Requirements of that Directive and associated EFTA regulations.
NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk
management process needs to be in compliance with 90/385/EEC, as amended by 2007/47/EC. This means that risks
have to be reduced ‘as far as possible’, ‘to a minimum’, ‘to the lowest possible level’, ‘minimized’ or ‘removed’, according
to the wording of the corresponding essential requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with essential requirements
1, 4, 5, 8, 9 and 10 of the Directive.
NOTE 3 This Annex ZA is based on normative references according to the table of references in the European
foreword, replacing the references in the core text.
NOTE 4 When an Essential Requirement does not appear in Table ZA.1, it means that it is not addressed by this
European Standard.
Table ZA.1 — Correspondence between this European Standard and Directive 90/385/EEC
Clauses of this European Essential Requirements (ERs) of Qualifying remarks/Notes
Standard EU Directive 90/385/EEC
4, 5, 6, 7, 8, 9, 10 7 Only a sterilization process using
ionizing radiation is considered by
this standard.
This relevant Essential
Requirement is only partly
addressed in this European
Standard. Design and packaging
for maintenance of sterility during
transportation and storage are not
covered. Aspects of manufacture
other than those related to
sterilization are not covered.
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling within
the scope of this standard.
Annex ZB
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices
This European Standard has been prepared under a mandate given to CEN/CENELC by the European
Commission and the European Free Trade Association to provide a means of conforming to Essential
Requirements of the New Approach Directive 93/42/EEC on medical devices.
Once this standard is cited in the Official Journal of the European Union under that Directive and has been
implemented as a national standard in at least one Member State, compliance with the normative clauses of
this standard given in Table ZB.1 confers, within the limits of the scope of this standard, a presumption of
conformity with the corresponding Essential Requirements of that Directive and associated EFTA regulations.
NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk
management process needs to be in compliance with 93/42/EEC, as amended by 2007/47/EC. This means that risks have
to be reduced ‘as far as possible’, ‘to a minimum’, ‘to the lowest possible level’, ‘minimized’ or ‘removed’, according to the
wording of the corresponding essential requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with essential requirements
1, 2, 5, 6, 7, 8, 9, 11 and 12 of the Directive.
NOTE 3 This Annex ZA is based on normative references according to the table of references in the European
foreword, replacing the references in the core text.
NOTE 4 When an Essential Requirement does not appear in Table ZA.1, it means that it is not addressed by this
European Standard.
Table ZB.1 — Correspondence between this European Standard and EU Directive 93/42/EEC
Clauses of this European Essential Requirements (ERs) Qualifying remarks/Notes
Standard of EU Directive 93/42/EEC
4, 5, 6, 7, 8, 9, 10 8.3 Only a sterilization process using
inoizing radiation is considered by this
standard.
This relevant ER is only partly
addressed in this International
Standard and only in conjunction with
ISO 11137-1. Design and packaging
for maintenance of sterility during
transportation and storage are not
covered. Aspects of manufacture
other than those related to sterilization
are not covered.
4, 5, 6, 7, 8, 9, 10 8.4 This relevant ER is only partly
addressed in this International
Standard and only in conjunction with
ISO 11137-1. Aspects of manufacture
other than those related to sterilization
are not covered.
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling within
the scope of this standard.
Annex ZC
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 98/79/EC on in vitro diagnostic
medical devices
This European Standard has been prepared under a mandate given to CEN/CENELEC by the European
Commission and the European Free Trade Association to provide a means of conforming to Essential
Requirements of the New Approach Directive 98/79/EC on in vitro diagnostic medical devices.
Once this standard is cited in the Official Journal of the European Union under that Directive and has been
implemented as a national standard in at least one Member State, compliance with the normative clauses of
this standard given in Table ZC.1 confers, within the limits of the scope of this standard, a presumption of
conformity with the corresponding Essential Requirements of that Directive and associated EFTA regulations.
NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk
management process needs to be in compliance with 98/79/EC. This means that risks have to be reduced ‘as far as
possible’, ‘to a minimum’, ‘to the lowest possible level’, ‘minimized’ or ‘removed’, according to the wording of the
corresponding essential requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with essential requirements
Part A: 1, 2 and 5; Part B: 1.2, 2, 3, 5, 6, and 7 of the Directive.
NOTE 3 This Annex ZA is based on normative references according to the table of references in the European
foreword, replacing the references in the core text.
NOTE 4 When an Essential Requirement does not appear in Table ZA.1, it means that it is not addressed by this
European Standard.
Table ZC.1 — Correspondence between this European Standard and Directive 98/79/EC
Clauses of this European Essential Requirements (ERs) of Qualifying remarks/Notes
Standard EU Directive 98/79/EC
4, 5, 6, 7, 8, 9, 10 B.2.3 Only a sterilization process using
inoizing radiation is considered by
this standard.
This relevant ER is only partly
addressed in this International
Standard and only in conjunction
with ISO 11137-1. Design and
packaging for maintenance of
sterility during transportation and
storage are not covered. Aspects
of manufacture other than those
related to sterilization are not
covered.
4, 5, 6, 7, 8, 9, 10 B.2.4 This relevant Essential requirement
is addressed in this International
Standard in conjunction with
ISO 11137-1 and only with regard
to:
- sterilization, not covering other
special microbiological state
- devices for which sterilization by
radiation is appropriate .
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling within
the scope of this standard.
INTERNATIONAL ISO
STANDARD 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
ISO 11137-2:2013(E)
© 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
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Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail copyright@iso.org
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Published in Switzerland
ii © ISO 2013 – All rights reserved

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
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 .37
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
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
15 46
Method VD .
max
10.4 Failure of a sterilization dose audit .52
11 Worked examples .52
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

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 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
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
[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
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

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: 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 11137-2:2013(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
2 © ISO 2013 – All rights reserved

ISO 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
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 1 to entry: 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 1 to entry: For the purposes of this part of ISO 11137, D applies to the radiation dose only and not to time.
ISO 11137-2:2013(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 substan-
tiation, 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.
4.2 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;
4 © ISO 2013 – All rights reserved

ISO 11137-2:2013(E)
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 verifica-
tion 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).
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;
ISO 11137-2:2013(E)
f) complexity of product;
g) degree of automation during manufacture;
h) manufacturing environment.
4.3.2 Master product
...