EN ISO 11137-2:2006

SLOVENSKI STANDARD
01-julij-2006
1DGRPHãþD
OSIST prEN ISO 11137-2:2004
SIST EN 552:2000
SIST EN 552:2000/A1:2000
SIST EN 552:2000/A2:2001
6WHULOL]DFLMDL]GHONRY]D]GUDYVWYHQRQHJR6HYDQMHGHO'RORþDQMHRGPHUND
VWHULOL]DFLMH,62
Sterilization of health care products - Radiation - Part 2: Establishing the sterilization
dose (ISO 11137-2:2006)
Sterilisation von Produkten für die Gesundheitsfürsorge - Strahlen - Teil 2: Festlegung
der Sterilisationsdosis (ISO 11137-2:2006)
Stérilisation des produits de santé - Irradiation - Partie 2: Établissement de la dose de
stérilisation (ISO 11137-2:2006)
Ta slovenski standard je istoveten z: EN ISO 11137-2:2006
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
April 2006
ICS 11.080.01 Supersedes EN 552:1994
English Version
Sterilization of health care products - Radiation - Part 2:
Establishing the sterilization dose (ISO 11137-2:2006)
Stérilisation des produits de santé - Irradiation - Partie 2: Sterilisation von Produkten für die Gesundheitsfürsorge -
Établissement de la dose de stérilisation (ISO 11137- Strahlen - Teil 2: Festlegung der Sterilisationsdosis (ISO
2:2006) 11137-2:2006)
This European Standard was approved by CEN on 13 April 2006.
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 Central Secretariat 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 Central Secretariat has the same status as the official
versions.
CEN members are the national standards bodies of Austria, Belgium, Cyprus, Czech Republic, Denmark, Estonia, Finland, France,
Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania,
Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: rue de Stassart, 36  B-1050 Brussels
© 2006 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 11137-2:2006: E
worldwide for CEN national Members.

Foreword
This document (EN ISO 11137-2:2006) 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 October 2006, and conflicting national standards
shall be withdrawn at the latest by April 2009.

This document supersedes EN 552:1994.

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, 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, Cyprus,
Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland,
Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania,
Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.

Endorsement notice
The text of ISO 11137-2:2006 has been approved by CEN as EN ISO 11137-2:2006 without any
modifications.
ANNEX ZA
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directives 90/385/EEC concerning active
implantable medical devices, 93/42/EEC concerning medical devices
and 98/79/EEC concerning 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 one means of conforming to
Essential Requirements of the New Approach Directive, EU Directives 90/385/EEC concerning
active implantable medical devices, 93/42/EEC concerning medical devices and 98/79/EEC
concerning in vitro diagnostic medical devices.

Once this standard is cited in the Official Journal of the European Communities 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.

Table ZA.1 — Correspondence between this European Standard and EU Directives
90/385/EEC concerning active implantable medical devices, 93/42/EEC concerning medical
devices and 98/79/EEC concerning in vitro diagnostic medical devices

Clause(s)/Sub-clause(s) Essential Essential Essential Qualifying
of this European Requirements Requirements Requirements remarks/Notes
Standard (ERs) of Directive (ERs) of (ERs) of Directive
90/385/EEC Directive 98/79/EEC
93/42/EEC
In part
4, 5, 6, 7, 8, 9, 10, 11, 12 7 8.3 B.2.3
In part
4, 5, 6, 7, 8, 9, 10, 11, 12 8.4 B.2.4

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
First edition
2006-04-15
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 11137-2:2006(E)
©
ISO 2006
ISO 11137-2:2006(E)
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ii © ISO 2006 – All rights reserved

ISO 11137-2:2006(E)
Contents Page
Foreword. v
Introduction . vi
1 Scope .1
2 Normative references .1
3 Abbreviations, terms and definitions .1
3.1 Abbreviations.1
3.2 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 and verifying the sterilization dose .7
5.1 Nature of product.7
5.2 Sample item portion (SIP) .8
5.3 Manner of sampling.8
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 W 1,0 for multiple
production batches.11
7.3 Procedure for Method 1 for product with an average bioburden W 1,0 for a single
production batch.16
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.18
8 Method 2: Dose setting using fraction positive information from incremental dosing to
determine an extrapolation factor.18
8.1 Rationale.18
8.2 Procedure for Method 2A.19
8.3 Procedure for Method 2B.22
9 Method VD — Substantiation of 25 kGy or 15 kGy as the sterilization dose .25
max
9.1 Rationale.25
9.2 Procedure for Method VD for multiple production batches.26
max
9.3 Procedure for Method VD for a single production batch .29
max
9.4 Procedure for Method VD for multiple production batches.30
max
9.5 Procedure for Method VD for a single production batch .33
max
10 Auditing sterilization dose.34
10.1 Purpose and frequency.34
ISO 11137-2:2006(E)
10.2 Procedure for auditing a sterilization dose established using Method 1 or Method 2. 35
10.3 Procedure for auditing a sterilization dose substantiated using VD . 37
max
11 Worked examples. 41
11.1 Worked examples for Method 1. 41
11.2 Worked examples for Method 2. 44
11.3 Worked examples for Method VD . 53
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. 55
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. 56
11.6 Worked example of a sterilization dose audit for a sterilization dose substantiated using
Method VD .58
max
Bibliography . 59

iv © ISO 2006 – All rights reserved

ISO 11137-2:2006(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 first edition, together with ISO 11137-1 and ISO 11137-3, cancels and replaces ISO 11137:1995.
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 11137-2:2006(E)
Introduction
This part of ISO 11137 describes methods that may 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:
a) dose setting to obtain a product-specific dose;
b) 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
[17] [18]
ideas first propounded by Tallentire (Tallentire, 1973 ; Tallentire, Dwyer and Ley, 1971 ; Tallentire and
[19] [8]
Khan, 1978 ). Subsequently, standardized protocols were developed (Davis et al., 1981 ; Davis,
[9]
Strawderman and Whitby, 1984 ) which formed the basis of the dose setting methods detailed in the AAMI
[4], [6]
Recommended Practice for Sterilization by Gamma Radiation (AAMI 1984, 1991 ).
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 may 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 u 25 kGy. The basis of the method devised specifically for
[14]
substantiation of 25 kGy, Method VD , was put forward by Kowalski and Tallentire (1999) . Subsequent
max
evaluations involving computational techniques demonstrated that the underlying principles were soundly
[13]
based (Kowalski, Aoshuang and Tallentire, 2000) and field trials confirmed that Method VD is effective
max
in substantiating 25 kGy for a wide variety of medical devices manufactured and assembled in different ways
[16]
(Kowalski et al., 2002) .
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
[5]
sterilization — Substantiation of 25 kGy as a sterilization dose — Method VD (AAMI TIR27:2001) , a text
max
on 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 to substantiate that
–6
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 kGy, is included as a superscript to the VD symbol. Thus, for
max
substantiation of a sterilization dose of 25 kGy the method is designated VD .
max
15 25
Method VD is based on the same principles as Method VD described above. The test procedure is
max max
25 15
the same as Method VD , but VD is limited to product with average bioburden u 1,5. The outcomes
max max
–6
of these tests are used to substantiate that 15 kGy achieves a sterility assurance level of 10 .
This part of ISO 11137 also describes methods that may 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 2006 – All rights reserved

INTERNATIONAL STANDARD ISO 11137-2:2006(E)

Sterilization of health care products — Radiation —
Part 2:
Establishing the sterilization dose
1 Scope
This part of ISO 11137 specifies methods of 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 dose
auditing in order to demonstrate the continued effectiveness of the sterilization dose.
This part of ISO 11137 defines product families for dose establishment and dose auditing.
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 the
population of microorganisms on product
ISO 11737-2, Sterilization of medical devices — Microbiological methods — Part 2: Test of sterility performed
in the validation of a sterilization process
ISO 13485, Medical devices — Quality management systems — Requirements for regulatory purposes
3 Abbreviations, terms and definitions
For purposes of this document, the terms and definitions given in ISO 11137-1 and the following apply.
3.1 Abbreviations
3.1.1
A
dose to adjust the median ffp dose downwards, to the FFP dose
3.1.2
CD*
number of positive tests of sterility obtained from tests performed individually on 100 product items irradiated
in a Method 2 verification dose experiment
ISO 11137-2:2006(E)
3.1.3
d *
dose derived from an incremental dose experiment performed on product items drawn from a given production
batch
3.1.4
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 3 d * values derived for a given product.
3.1.5
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
3.1.6
DD*
dose delivered in a Method 2 verification dose experiment
3.1.7
DS
estimate of D value of microorganisms present on product after exposure to DD*
3.1.8
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]
NOTE For the purposes of this document, D applies to the radiation dose only and not to time.
3.1.9
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
3.1.10
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 3 ffp doses
3.1.11
First No Positive dose
FNP
–2
estimate of the dose to provide an SAL of 10 for the test items, which is used in the calculation of DS
3.1.12
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
3.1.13
VD
max
maximal verification dose for a given bioburden, consistent with the attainment of an SAL of 10–6 at a
specified sterilization dose of 25 kGy
2 © ISO 2006 – All rights reserved

ISO 11137-2:2006(E)
3.2 Terms
3.2.1
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]
3.2.2
bioburden
population of viable microorganisms on or in product and/or sterile barrier system
[ISO/TS 11139:2006]
3.2.3
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
3.2.4
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
3.2.5
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
3.2.6
negative test of sterility
test result for which there is no detectable microbial growth from product, or portion thereof, subjected to a test
of sterility
3.2.7
packaging system
combination of the sterile barrier system and protective packaging
[ISO/TS 11139:2006]
3.2.8
positive test of sterility
test result for which there is detectable microbial growth from product, or portion thereof, subjected to a test of
sterility
3.2.9
sample item portion
SIP
defined portion of a health care product that is tested
3.2.10
sterile barrier system
minimum package that prevents ingress of microorganisms and allows aseptic presentation of product at the
point of use
ISO 11137-2:2006(E)
3.2.11
sterility assurance level
SAL
probability of a single viable microorganism occurring on an item after sterilization
[ISO/TS 11139:2006]
–6 –3
NOTE The term sterility assurance level takes a quantitative value, generally 10 or 10 . When applying this
–6
quantitative value to assurance of sterility, an SAL of 10 has a lower value but provides a greater assurance of sterility
–3
than an SAL of 10 .
3.2.12
sterilization dose audit
exercise undertaken to confirm the appropriateness of an established sterilization dose
3.2.13
verification dose
–2
dose of radiation predicted to give a predetermined SAL W 10 used in establishing the sterilization dose
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 number and types of microorganism 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 in establishing the sterilization dose and for sterilization dose auditing, 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;
b) components;
c) product design and size;
d) manufacturing process;
e) manufacturing equipment;
4 © ISO 2006 – All rights reserved

ISO 11137-2:2006(E)
f) manufacturing environment;
g) manufacturing location.
The outcome of the assessment and considerations shall be recorded (see 4.1.2 of ISO 11137-1:2006).
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 4.1.2 of ISO 11137-1:2006). 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 microorganism 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) numbers of microorganisms comprising the bioburden;
b) the environment in which the microorganisms occur;
c) size of product;
d) number of components;
e) complexity of product;
f) degree of automation during manufacture;
g) manufacturing environment.
ISO 11137-2:2006(E)
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 product family in accordance with 4.3.3.
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 planned schedule 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 may 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 which 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.
4.4 Maintaining product families
4.4.1 Periodic review
Review shall be performed at a specified frequency to assure 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 review shall be
performed at least annually. The outcome of the review shall be recorded in accordance with 4.1.2 of
ISO 11137-1:2006.
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 4.1.2 of ISO 11137-1:2006).
6 © ISO 2006 – All rights reserved

ISO 11137-2:2006(E)
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 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 and verifying 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 its packaging system;
d) a kit comprising a variety of procedure-related health care products.
Product items for the performance of dose setting and dose substantiation shall be taken in accordance with
Table 1.
Table 1 — Nature of product items for establishing and verifying 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
SAL associated with that packaging
system might be higher.
Kit of procedure-related health care
Each type of health care product Each health care product is used
a
comprising the kit independently in clinical practice.
products
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 setting, the sterilization dose is chosen based on the health care product requiring the highest sterilization dose.
ISO 11137-2:2006(E)
5.1.2 If the product has a claim of sterility for part of the product, the sterilization dose may 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 may 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 equal to or greater than 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 (sample item portion) may be substituted. The SIP
should be as large a portion of item as practicable in order to manipulate in the laboratory, and should be of a
size that can be handled during testing.
5.2.2 For a product with an average bioburden equal to or less than 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 portions of product selected at
random, which proportionally represent each of the materials from which the product is made. If the bioburden
distribution is known, the SIP may be selected from the portion of the product that is considered to be the
most severe challenge to the sterilization process.
The value of SIP can be calculated on the basis of length, mass, volume or surface area (see Table 2 for
examples).
Table 2 — Examples for calculation of SIP
Basis for SIP Product
Length Tubing (consistent diameter)
Powders
Mass Gowns
Implants (absorbable)
Volume Fluid
Implants (non-absorbable)
Surface area
Tubing (variable diameter)
5.2.4 The preparation and packaging of a sample item portion shall be carried out under conditions that
minimize alterations to bioburden. Environmentally-controlled conditions should be used for preparation of
SIPs and, whenever possible, packaging materials should be equivalent to those used for the finished product.
5.2.5 The adequacy of a selected SIP shall be demonstrated. The bioburden of the SIP shall be such that
tests of sterility performed individually on 20 non-irradiated SIP items yield a minimum of 17 positive tests of
sterility (i.e. 85 % positives). If the criterion is not achieved, a SIP larger than that examined originally and that
meets the criterion shall be used. If an entire product is tested (SIP equal to 1,0), the criterion of a minimum of
17 positive tests of sterility observed out of 20 tests of sterility performed does not have to be met.
5.3 Manner of sampling
5.3.1 Product for establishing or auditing the sterilization dose shall be representative of that subjected to
routine processing procedures and conditions. Generally, each product item used for a bioburden
determination or in the performance of a test of sterility should be taken from a separate packaging system.
8 © ISO 2006 – All rights reserved

ISO 11137-2:2006(E)
5.3.2 The period of time that elapses between the selection of product samples and the determination of
bioburden should reflect the time period between completion of the last manufacturing step and sterilization of
product. Product items may be selected from product rejected during the manufacturing process provided that
they have been subjected to the same processing and conditions as the remainder of production.
5.4 Microbiological testing
5.4.1 Bioburden determinations and tests of sterility shall be conducted in accordance with ISO 11737-1
and ISO 11737-2, respectively.
Soybean Casein Digest Broth, with an incubation temperature of (30 ± 2) °C and an incubation period of
14 days, is generally recommended when a single medium is used for the performance of tests of sterility. If
there is reason to suspect that this medium and temperature do not support the growth of microorganisms
[12]
present, other appropriate media and incubation conditions should be used. See, e.g., Herring et al, 1974 ;
[10] [7]
Favero, 1971 ; NHB 5340.1A, 1968 .
Whenever practicable, product the should be irradiated in its original form and package system. However, to
reduce the possibility of false positives in the test of sterility, an item may be disassembled and repackaged
prior to irradiation. Manipulations prior to irradiation are not acceptable if they change the magnitude of the
bioburden or its response to radiation (i.e. manipulations that alter the chemical environment in the vicinity of
the microorganisms, typically oxygen tension). Materials for repackaging product items for irradiation shall be
capable of withstanding the doses delivered and subsequent handling, thereby minimizing the likelihood of
contamination.
5.4.2 Bioburden determinations shall be carried out on a product that has undergone the packaging process.
NOTE Generally, it is sufficient to perform a bioburden determination on a product after its removal from its
packaging system and to omit the packaging system from the determination.
5.5 Irradiation
5.5.1 Irradiation of a product in establishing and verifying the sterilization dose shall be conducted in an
irradiator that has undergone Installation Qualification, Operational Qualification and Performance
Qualification, in accordance with ISO 11137-1. For the performance of a verification dose experiment or an
incremental dose experiment, sufficient dose mapping shall be carried out to identify the highest and the
lowest doses received by product.
5.5.2 Dose measurements and the use of radiation sources shall be in accordance with ISO 11137-1.
NOTE See ISO 11137-3 fo
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