SIST EN ISO 11137-2:2006
(Main)Sterilization of health care products - Radiation - Part 2: Establishing the sterilization dose (ISO 11137-2:2006)
Sterilization of health care products - Radiation - Part 2: Establishing the sterilization dose (ISO 11137-2:2006)
20060421 - DOW = DAV+36 months
2006-03-23 Final text (foreword) to be validated by TC Secretary before Publication.
2003-03-31 WIs 00207031 & 032 merged further to merging at ISO level (NT).
Sterilisation von Produkten für die Gesundheitsfürsorge - Strahlen - Teil 2: Festlegung der Sterilisationsdosis (ISO 11137-2:2006)
Dieser Teil von ISO 11137 legt Verfahren zur Ermittlung der Mindestdosis, die zur Erreichung einer festgelegten Anforderung an die Sterilität erforderlich ist, und Verfahren zur Bestätigung der Anwendung von 25 kGy oder 15 kGy als Sterilisationsdosis zur Erreichung eines Sterilitätssicherheitsniveaus, SAL, von 10–6 fest. Dieser Teil von ISO 11137 legt auch Verfahren der Dosisüberprüfung zum Nachweis der fortgesetzten Wirksamkeit der Sterilisationsdosis fest.
Dieser Teil von ISO 11137 definiert Produktfamilien für die Dosisfestlegung und Dosisüberprüfung.
Stérilisation des produits de santé - Irradiation - Partie 2: Établissement de la dose de stérilisation (ISO 11137-2:2006)
Sterilizacija izdelkov za zdravstveno nego - Sevanje - 2. del: Določanje odmerka sterilizacije (ISO 11137-2:2006)
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 11137-2:2006
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
SIST EN ISO 11137-2:2006 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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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.
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EN ISO 11137-2:2006 (E)
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.
2
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EN ISO 11137-2:2006 (E)
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.
3
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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
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ISO 11137-2:2006(E)
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ii © ISO 2006 – All rights reserved
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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
25
9.2 Procedure for Method VD for multiple production batches.26
max
25
9.3 Procedure for Method VD for a single production batch .29
max
15
9.4 Procedure for Method VD for multiple production batches.30
max
15
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 2006 – All rights reserved iii
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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
25
Method VD .58
max
Bibliography . 59
iv © ISO 2006 – All rights reserved
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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 2006 – All rights reserved v
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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
10
probability that an item will possess a surviving microorganism after exposure to a given dose of radiation is
defined in terms of the initial number of microorganisms on the item prior to irradiation and the D values of
10
the microorganisms. The methods involve performance of tests of sterility on product items that have received
doses of radiation lower than the sterilization dose. The outcome of these tests is used to predict the dose
needed to achieve a predetermined sterility assurance level, SAL.
Methods 1 and 2 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
25
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
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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 2006 – All rights reserved 1
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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*
10
3.1.8
D value
D value
10
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.
10
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
15
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
25
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
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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 2006 – All rights reserved 3
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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
...
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