SIST EN ISO 11137-3:2017
(Main)Sterilization of health care products - Radiation - Part 3: Guidance on dosimetric aspects of development, validation and routine control (ISO 11137-3:2017)
Sterilization of health care products - Radiation - Part 3: Guidance on dosimetric aspects of development, validation and routine control (ISO 11137-3:2017)
This document gives guidance on meeting the requirements in ISO 11137-1 and ISO 11137-2 and in
ISO/TS 13004 relating to dosimetry and its use in development, validation and routine control of a
radiation sterilization process.
Sterilisation von Produkten für die Gesundheitsfürsorge - Strahlen - Teil 3: Anleitung zu dosimetrischen Aspekten der Entwicklung, Validierung und Lenkung der Anwendung (ISO 11137-3:2017)
Dieses Dokument gibt eine Anleitung zur Erfüllung der Anforderungen von ISO 11137-1 und ISO 11137-2 und ISO/TS 13004 hinsichtlich der Dosimetrie und ihrem Gebrauch bei der Entwicklung, Validierung und Lenkung der Anwendung eines Strahlensterilisationsverfahrens.
Stérilisation des produits de santé - Irradiation - Partie 3: Directives relatives aux aspects dosimétriques de développement, la validation et le contrôle de routine (ISO 11137-3:2017)
L'ISO 11137-3:2017 fournit des préconisations permettant de satisfaire aux exigences de l'ISO 11137‑1, l'ISO 11137‑2 et l'ISO/TS 13004 concernant la dosimétrie et son utilisation dans la mise au point, la validation et le contrôle de routine d'un procédé de stérilisation par irradiation.
Sterilizacija izdelkov za zdravstveno nego - Sevanje - 3. del: Smernice o dozimetričnih vidikih za razvoj, validacijo in rutinski nadzor (ISO 11137-3:2017)
Ta dokument podaja smernice za izpolnjevanje zahtev v standardih ISO 11137-1 in ISO 11137-2 ter
standardu ISO/TS 13004, ki določa zahteve za razvoj, validacijo in rutinski nadzor sterilizacijskega postopka s sevanjem.
General Information
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Related Packages
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 11137-3:2017
01-oktober-2017
1DGRPHãþD
SIST EN ISO 11137-3:2006
6WHULOL]DFLMDL]GHONRY]D]GUDYVWYHQRQHJR6HYDQMHGHO 6PHUQLFHR
GR]LPHWULþQLKYLGLNLK]DUD]YRMYDOLGDFLMRLQUXWLQVNLQDG]RU ,62
Sterilization of health care products - Radiation - Part 3: Guidance on dosimetric aspects
of development, validation and routine control (ISO 11137-3:2017)
Sterilisation von Produkten für die Gesundheitsfürsorge - Strahlen - Teil 3: Anleitung zu
dosimetrischen Aspekten der Entwicklung, Validierung und Lenkung der Anwendung
(ISO 11137-3:2017)
Stérilisation des produits de santé - Irradiation - Partie 3: Directives relatives aux aspects
dosimétriques de développement, la validation et le contrôle de routine (ISO 11137-
3:2017)
Ta slovenski standard je istoveten z: EN ISO 11137-3:2017
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
SIST EN ISO 11137-3:2017 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 11137-3:2017
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SIST EN ISO 11137-3:2017
EN ISO 11137-3
EUROPEAN STANDARD
NORME EUROPÉENNE
July 2017
EUROPÄISCHE NORM
ICS 11.080.01 Supersedes EN ISO 11137-3:2006
English Version
Sterilization of health care products - Radiation - Part 3:
Guidance on dosimetric aspects of development, validation
and routine control (ISO 11137-3:2017)
Stérilisation des produits de santé - Irradiation - Partie Sterilisation von Produkten für die
3: Directives relatives aux aspects dosimétriques de Gesundheitsfürsorge - Strahlen - Teil 3: Anleitung zu
développement, la validation et le contrôle de routine dosimetrischen Aspekten der Entwicklung, Validierung
(ISO 11137-3:2017) und Lenkung der Anwendung (ISO 11137-3:2017)
This European Standard was approved by CEN on 15 March 2017.
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, Serbia, 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
© 2017 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 11137-3:2017 E
worldwide for CEN national Members.
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SIST EN ISO 11137-3:2017
EN ISO 11137-3:2017 (E)
Contents Page
European foreword . 3
2
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SIST EN ISO 11137-3:2017
EN ISO 11137-3:2017 (E)
European foreword
This document (EN ISO 11137-3:2017) 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 January 2018 and conflicting national standards shall
be withdrawn at the latest by January 2018.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 11137-3:2006.
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, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
the United Kingdom.
Endorsement notice
The text of ISO 11137-3:2017 has been approved by CEN as EN ISO 11137-3:2017 without any
modification.
3
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SIST EN ISO 11137-3:2017
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SIST EN ISO 11137-3:2017
INTERNATIONAL ISO
STANDARD 11137-3
Second edition
2017-06
Sterilization of health care products —
Radiation —
Part 3:
Guidance on dosimetric aspects of
development, validation and routine
control
Stérilisation des produits de santé — Irradiation —
Partie 3: Directives relatives aux aspects dosimétriques de
développement, la validation et le contrôle de routine
Reference number
ISO 11137-3:2017(E)
©
ISO 2017
---------------------- Page: 7 ----------------------
SIST EN ISO 11137-3:2017
ISO 11137-3:2017(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2017, Published in Switzerland
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
Ch. de Blandonnet 8 • CP 401
CH-1214 Vernier, Geneva, Switzerland
Tel. +41 22 749 01 11
Fax +41 22 749 09 47
copyright@iso.org
www.iso.org
ii © ISO 2017 – All rights reserved
---------------------- Page: 8 ----------------------
SIST EN ISO 11137-3:2017
ISO 11137-3:2017(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms, definitions and symbols . 1
3.1 General . 1
3.2 Symbols . 3
4 Measurement of dose. 4
4.1 General . 4
4.1.1 Direct and indirect dose measurements . 4
4.1.2 Dosimetry systems . 4
4.1.3 Best estimate of dose . 4
4.2 Dosimetry system selection and calibration . 5
4.2.1 General. 5
4.2.2 Selection of dosimetry systems . 5
4.2.3 Calibration of dosimetry systems . 5
4.3 Dose measurement uncertainty . 6
4.3.1 General concepts . 6
4.3.2 The Guide to the expression of uncertainty in measurement
(GUM) methodology . 6
4.3.3 Radiation sterilization specific aspects of dose measurement uncertainty . 7
5 Establishing the maximum acceptable dose. 8
6 Establishing the sterilization dose . 9
7 Installation qualification .10
8 Operational qualification .11
8.1 General .11
8.2 Gamma irradiators .11
8.3 Electron beam irradiators .13
8.4 X-ray irradiators .15
9 Performance qualification .17
9.1 General .17
9.2 Gamma irradiators .18
9.2.1 Loading pattern .18
9.2.2 Dosimetry.19
9.2.3 Analysis of dose mapping data .20
9.3 Electron beam irradiators .20
9.3.1 Loading pattern .20
9.3.2 Dosimetry.22
9.3.3 Analysis of dose mapping data .23
9.4 X-ray irradiators .23
9.4.1 Loading pattern .23
9.4.2 Dosimetry.24
9.4.3 Analysis of dose mapping data .25
10 Routine monitoring and control .25
10.1 General .25
10.2 Frequency of dose measurements .26
Annex A (informative) Mathematical modelling .27
Annex B (informative) Tables of references for dosimetry-related testing during IQ/OQ/PQ .30
© ISO 2017 – All rights reserved iii
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SIST EN ISO 11137-3:2017
ISO 11137-3:2017(E)
Annex C (informative) Tolerances associated with doses used in sterilization dose setting/
substantiation in ISO 11137-2 and ISO/TS 13004 .33
Annex D (informative) Application of dose measurement uncertainty in setting process
target doses .34
Bibliography .40
iv © ISO 2017 – All rights reserved
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SIST EN ISO 11137-3:2017
ISO 11137-3:2017(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.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).
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. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www .iso .org/ patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO’s adherence to the
World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see the following
URL: w w w . i s o .org/ iso/ foreword .html.
This document was prepared by Technical committee ISO/TC 198, Sterilization of health care products.
This second edition cancels and replaces the first edition (ISO 11137-3:2006), which has been technically
revised.
A list of all parts in the ISO 11137 series can be found on the ISO website.
© ISO 2017 – All rights reserved v
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SIST EN ISO 11137-3:2017
ISO 11137-3:2017(E)
Introduction
An integral part of radiation sterilization is the ability to measure dose. Dose is measured during
all stages of development, validation and routine monitoring of the sterilization process. It has to
be demonstrated that dose measurement is traceable to a national or an International Standard,
that the uncertainty of measurement is known, and that the influence of temperature, humidity and
other environmental considerations on dosimeter response is known and taken into account. Process
parameters are established and applied based on dose measurements. This document provides
guidance on the use of dose measurements (dosimetry) during all stages in the development, validation
and routine control of the radiation sterilization process.
Requirements in regard to dosimetry are given in ISO 11137-1 and ISO 11137-2 and ISO/TS 13004.
This document gives guidance to these requirements. The guidance given is not normative and is
not provided as a checklist for auditors. The guidance provides explanations and methods that are
regarded as being suitable means for complying with the requirements. Methods other than those
given in the guidance may be used, if they are effective in achieving compliance with the requirements
of ISO 11137-1, ISO 11137-2 and ISO/TS 13004.
vi © ISO 2017 – All rights reserved
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SIST EN ISO 11137-3:2017
INTERNATIONAL STANDARD ISO 11137-3:2017(E)
Sterilization of health care products — Radiation —
Part 3:
Guidance on dosimetric aspects of development, validation
and routine control
1 Scope
This document gives guidance on meeting the requirements in ISO 11137-1 and ISO 11137-2 and in
ISO/TS 13004 relating to dosimetry and its use in development, validation and routine control of a
radiation sterilization process.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements 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, Sterilization of health care products — Radiation — Part 1: Requirements for development,
validation and routine control of a sterilization process for medical devices
ISO 11137-2, Sterilization of health care products — Radiation — Part 2: Establishing the sterilization dose
ISO/TS 13004, Sterilization of health care products — Radiation — Substantiation of a selected sterilization
SD
dose: Method VD
max
ISO 13485, Medical devices — Quality management systems — Requirements for regulatory purposes
3 Terms, definitions and symbols
For the purposes of this document, the terms and definitions given in ISO 11137-1 and ISO 11137-2 and
the following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— IEC Electropedia: available at http:// www .electropedia .org/
— ISO Online browsing platform: available at http:// www .iso .org/ obp
3.1 General
3.1.1
absorbed dose
dose
quantity of ionizing radiation energy imparted per unit mass of a specified material
[SOURCE: ISO 11137-1:2006, 3.1, modified]
Note 1 to entry: For the purposes of this document, the term “dose” is used to mean “absorbed dose”.
© ISO 2017 – All rights reserved 1
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SIST EN ISO 11137-3:2017
ISO 11137-3:2017(E)
3.1.2
combined standard measurement uncertainty
standard measurement uncertainty (3.1.13) that is obtained using the individual standard measurement
uncertainties associated with the input quantities in a measurement model
[SOURCE: VIM 2012, 2.31]
3.1.3
coverage factor
number larger than one by which a combined standard measurement uncertainty (3.1.2) is multiplied to
obtain an expanded measurement uncertainty (3.1.7)
Note 1 to entry: A coverage factor is usually symbolized as “k” (see also the GUM: 1995, 2.3.6).
3.1.4
direct dose measurement
measurement of absorbed dose (3.1.1) with a dosimeter at the location of interest
Note 1 to entry: For example, a direct measurement of minimum dose is made with a dosimeter at the minimum
dose location in an irradiation container.
3.1.5
dose uniformity ratio
ratio of the maximum to the minimum absorbed dose (3.1.1) within the irradiation container
3.1.6
dosimetry system
interrelated elements used for determining absorbed dose (3.1.1), including dosimeters, instruments,
associated reference standards and procedures for their use
[SOURCE: ISO/TS 11139:2006, 2.15]
3.1.7
expanded measurement uncertainty
product of a combined standard measurement uncertainty (3.1.2) and a factor larger than the number one
Note 1 to entry: The factor depends on the type of probability distribution of the output quantity in a measurement
model and on the selected coverage probability.
Note 2 to entry: The term “factor” in this definition refers to a coverage factor.
3.1.8
indirect dose measurement
measurement of absorbed dose (3.1.1) at a location remote from a directly measured dosimeter,
calculated by the application of factors
Note 1 to entry: For example, where the minimum dose in an irradiation container cannot easily be measured
directly, a dosimeter placed in a remote location may be measured and factors applied to that measurement to
calculate the minimum dose.
3.1.9
scan length
dimension of the irradiation zone, perpendicular to the scan width and direction of the electron beam
at a specified distance from the accelerator window
Note 1 to entry: ISO/ASTM standards use “beam length” to mean the same thing that “scan length” means in this
document. This document uses “scan length” for consistency with ISO 11137-1.
2 © ISO 2017 – All rights reserved
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SIST EN ISO 11137-3:2017
ISO 11137-3:2017(E)
3.1.10
scan width
dimension of the irradiation zone in the direction that the beam is scanned, perpendicular to the scan
length and direction of the electron beam at a specified distance from the accelerator window
Note 1 to entry: ISO/ASTM standards use “beam width” to mean the same thing that “scan width” means in this
document.
3.1.11
simulated product
material with attenuation and scattering properties similar to those of the product, material or
substance to be irradiated
Note 1 to entry: Simulated product is used as a substitute for the actual product, material or substance to be
irradiated. When used in routine production runs in order to compensate for the absence of product, simulated
product is sometimes referred to as compensating dummy. When used for absorbed dose mapping, simulated
product is sometimes referred to as “phantom material”.
Note 2 to entry: In this document, “dose mapping” is used for “absorbed dose mapping.”
3.1.12
spatial resolution
resolution in two dimensions
Note 1 to entry: Ability to detect change in dose in two dimensions.
3.1.13
standard measurement uncertainty
uncertainty of the result of a measurement expressed as a standard deviation
[SOURCE: VIM 2012, 2.30, modified]
3.1.14
uncertainty budget
statement of a measurement uncertainty, of the components of that measurement uncertainty, and of
their calculation and combination
Note 1 to entry: An uncertainty budget should include the measurement model, estimates and measurement
uncertainties associated with the quantities in the measurement model, covariances, type of applied probability
density functions, degrees of freedom, type of evaluation of measurement uncertainty and any coverage factor.
[SOURCE: VIM 2012, 2.33]
3.2 Symbols
Symbol Meaning
maximum acceptable dose determined in accord-
D
max,acc
ance with ISO 11137-1:2006, 8.1
sterilization dose determined in accordance with
D
ster
ISO 11137-1:2006, 8.2
direct measurement of maximum dose in a given
D
max
irradiation container
direct measurement of minimum dose in a given
D
min
irradiation container
direct measurement of dose at the routine monitor-
D
mon
ing position
ratio of maximum to minimum dose (D /D )
max min
R
max/min
determined by dose mapping
© ISO 2017 – All rights reserved 3
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SIST EN ISO 11137-3:2017
ISO 11137-3:2017(E)
Symbol Meaning
ratio of maximum to monitor dose (D /D )
max mon
R
max/mon
determined by dose mapping
ratio of minimum to monitor dose (D /D )
min mon
R
min/mon
determined by dose mapping
ster
D = D /R
mon ster min/mon
Dose at monitoring positions that correlate to dose
max,acc specifications
D = D /R
mon max,acc max/mon
calculated dose at the routine monitoring position
used for establishing process parameters that en-
lower
D
target
sures at a specified level of confidence that D is
ster
met or exceeded during routine processing
calculated dose at the routine monitoring position
used for establishing process parameters that en-
upper
D
target
sures at a specified level of confidence that D
max,acc
is not exceeded during routine processing
4 Measurement of dose
4.1 General
4.1.1 Direct and indirect dose measurements
The term “dose measurement” is used in this document as a general term to indicate the determination
of absorbed dose. It can refer both to a direct measurement of dose by a dosimeter at the location of
interest or to an indirect measurement of dose which relates to the calculation of the absorbed dose at
a location remote from a directly measured dose by the application of factors. The factors associated
with an indirect measurement of dose are usually determined during operational qualification (OQ)
and performance qualification (PQ) studies and reflect ratios of doses at different locations for a given
irradiation process. If the factors and their associated uncertainties have been determined using
traceable dose measurements, then the indirect measurement can itself be regarded as traceable and
will fulfil the requirements of ISO 11137-1 in terms of measurement traceability and uncertainty.
4.1.2 Dosimetry systems
ISO 10012 or ISO 13485 (see also ISO 11137-1) provide requirements for all aspects of the dosimetry
system(s) used. The dosimetry system(s) need to be included in a formal measurement management
system, as defined in ISO 10012, which sets out quality procedures to achieve metrological confirmation
and continual control of the measurement processes. An important aspect of this is the competence
and training of staff involved, both in the calibration and operation of the dosimetry system(s), and
also in the performance and analysis of dose measurements. Activities such as the choice of location of
dosimeters for dose mapping and the analysis of the resultant data require specific skills and training.
NOTE Examples of general requirements for dosimetry in radiation processing are given in Reference [19]
and further guidance on dose ma
...
SLOVENSKI STANDARD
oSIST prEN ISO 11137-3:2015
01-september-2015
6WHULOL]DFLMDL]GHONRY]D]GUDYVWYHQRQHJR6HYDQMHGHO 6PHUQLFHR
GR]LPHWULþQLKYLGLNLK]DUD]YRMYDOLGDFLMRLQUXWLQVNLQDG]RU ,62',6
Sterilization of health care products - Radiation - Part 3: Guidance on dosimetric aspects
of development, validation and routine control (ISO/DIS 11137-3:2015)
Sterilisation von Produkten für die Gesundheitsfürsorge - Strahlen - Teil 3: Anleitung zu
dosimetrischen Aspekten der Entwicklung, Validierung und Lenkung der Anwendung
(ISO/DIS 11137-3:2015)
Stérilisation des produits de santé - Irradiation - Partie 3: Directives relatives aux aspects
dosimétriques de développement, la validation et le contrôle de routine (ISO/DIS 11137-
3:2015)
Ta slovenski standard je istoveten z: prEN ISO 11137-3 rev
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
oSIST prEN ISO 11137-3:2015 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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oSIST prEN ISO 11137-3:2015
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oSIST prEN ISO 11137-3:2015
DRAFT INTERNATIONAL STANDARD
ISO/DIS 11137-3
ISO/TC 198 Secretariat: ANSI
Voting begins on: Voting terminates on:
2015-07-02 2015-10-02
Sterilization of health care products — Radiation —
Part 3:
Guidance on dosimetric aspects of development, validation
and routine control
Stérilisation des produits de santé — Irradiation —
Partie 3: Directives relatives aux aspects dosimétriques de développement, la validation et le contrôle de routine
ICS: 11.080.01
ISO/CEN PARALLEL PROCESSING
This draft has been developed within the International Organization for
Standardization (ISO), and processed under the ISO lead mode of collaboration
as defined in the Vienna Agreement.
This draft is hereby submitted to the ISO member bodies and to the CEN member
bodies for a parallel five month enquiry.
Should this draft be accepted, a final draft, established on the basis of comments
received, will be submitted to a parallel two-month approval vote in ISO and
THIS DOCUMENT IS A DRAFT CIRCULATED
formal vote in CEN.
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
To expedite distribution, this document is circulated as received from the
IN ADDITION TO THEIR EVALUATION AS
committee secretariat. ISO Central Secretariat work of editing and text
BEING ACCEPTABLE FOR INDUSTRIAL,
composition will be undertaken at publication stage.
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
STANDARDS MAY ON OCCASION HAVE TO
BE CONSIDERED IN THE LIGHT OF THEIR
POTENTIAL TO BECOME STANDARDS TO
WHICH REFERENCE MAY BE MADE IN
Reference number
NATIONAL REGULATIONS.
ISO/DIS 11137-3:2015(E)
RECIPIENTS OF THIS DRAFT ARE INVITED
TO SUBMIT, WITH THEIR COMMENTS,
NOTIFICATION OF ANY RELEVANT PATENT
RIGHTS OF WHICH THEY ARE AWARE AND TO
©
PROVIDE SUPPORTING DOCUMENTATION. ISO 2015
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oSIST prEN ISO 11137-3:2015
ISO/DIS 11137-3:2015(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2015, Published in Switzerland
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
Ch. de Blandonnet 8 • CP 401
CH-1214 Vernier, Geneva, Switzerland
Tel. +41 22 749 01 11
Fax +41 22 749 09 47
copyright@iso.org
www.iso.org
ii © ISO 2015 – All rights reserved
---------------------- Page: 4 ----------------------
oSIST prEN ISO 11137-3:2015
ISO/DIS 11137-3
Contents Page
Foreword . v
Introduction . vi
1 Scope . 1
2 Normative References . 1
3 Terms and definitions . 1
3.1 Definitions . 1
3.2 Terms . 3
3.2.1 Dose specification(s) . 3
3.2.2 Doses . 3
3.2.3 Dose mapping ratios and their associated uncertainties . 3
3.2.4 Doses at monitoring positions that correlate to dose specifications . 3
3.2.5 Dose targets . 4
3.2.6 Uncertainty . 4
4 Measurement of Dose . 4
5 Measurement of dose to product . 5
5.1 Dosimetry system selection and calibration. 5
5.1.1 General . 5
5.1.2 Selection of dosimetry systems . 5
5.1.3 Calibration of dosimetry systems . 5
5.2 Dose Measurement Uncertainty . 6
5.2.1 General Concepts . 6
5.2.2 Radiation sterilization specific aspects and total dose measurement uncertainty, σ . 7
total
6 Establishing the maximum acceptable dose . 8
7 Establishing the sterilization dose . 9
8 Installation qualification . 10
9 Operational qualification . 11
9.1 General . 11
9.2 Gamma irradiators . 11
9.3 Electron beam irradiators . 13
9.4 X-ray irradiators . 14
10 Performance qualification . 16
10.1 General . 16
10.2 Gamma . 17
10.2.1 Loading Pattern . 17
10.2.2 Dosimetry . 18
10.2.3 Analysis of dose mapping data . 19
10.3 Electron beam . 19
10.3.1 Loading Pattern . 19
10.3.2 Dosimetry . 21
10.3.3 Analysis of dose mapping data . 22
10.4 X-Ray . 22
10.4.1 Loading Pattern . 22
10.4.2 Dosimetry . 23
10.4.3 Analysis of dose mapping data . 24
11 Routine monitoring and control . 24
11.1 General . 24
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11.2 Frequency of dose measurements . 24
Annex A (informative) Mathematical modelling . 26
A.1 Introduction . 26
A.2 Types of model . 26
A.2.1 General . 26
A.2.2 Point Kernel . 26
A.2.3 Monte Carlo . 26
A.3 Use of models . 27
A.3.1 Design of irradiators . 27
A.3.2 Operation of gamma and X-ray irradiators. 27
A.3.3 Operation of electron beam irradiators . 28
Annex B (informative) Tables of references for dosimetry-related testing during IQ/OQ/PQ . 29
B.1 Installation Qualification. 29
B.2 Operational Qualification. . 30
B.3 Performance Qualification . 31
Annex C (informative) Tolerances associated with doses used in sterilization dose
setting/substantiation in ISO 11137-2 . 32
Annex D (informative) Establishment and application of total uncertainty, σ . 33
total
D.1 General . 33
D.2 General Methods for Calculating σ . 35
total
D.3 Selection of k values . 35
D.4 Calculating process target dose values that take uncertainty into account . 36
Bibliography . 37
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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 11137-3 was prepared by Technical Committee ISO/TC 198, Sterilization of health care products,.
This second edition cancels and replaces the first edition and has been extensively revised.
ISO 11137 consists of the following parts, under the general title Sterilization of health care products —
Radiation:
Part 1: Requirements for development, validation and routine control of a sterilization process for medical
devices
Part 2: Part 2: Establishing the sterilization dose
Part 3: Guidance on dosimetric aspects of development, validation and routine control
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Introduction
An integral part of radiation sterilization is the ability to measure dose. Dose is measured during all
stages of development, validation and routine monitoring of the sterilization process. It has to be
demonstrated that dose measurement is traceable to a national or International Standard, that the
uncertainty of measurement is known, and that the influence of temperature, humidity and other
environmental considerations on dosimeter response is known and taken into account. Process
parameters are established and applied based on dose measurements. This part of ISO 11137
provides guidance on the use of dose measurements (dosimetry) during all stages in the
development, validation and routine control of the radiation sterilization process.
Requirements in regard to dosimetry are given in ISO 11137 parts 1 and 2 and ISO TS 13004. This
part of ISO 11137 gives guidance to these requirements. The guidance given is not normative and
is not provided as a checklist for auditors. The guidance provides explanations and methods that
are regarded as being suitable means for complying with the requirements. Methods other than
those given in the guidance may be used, if they are effective in achieving compliance with the
requirements of ISO 11137-1 and ISO 11137-2.
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DRAFT INTERNATIONAL STANDARD ISO/DIS 11137‐3
Sterilization of health care products — Radiation — Part 3:
Guidance on dosimetric aspects of development, validation and
routine control
1 Scope
This part of ISO 11137 gives guidance on meeting the requirements in ISO 11137 parts 1 and 2 and in ISO
TS 13004 relating to dosimetry and its use in development, validation and routine control of a radiation
sterilization process.
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, Sterilization of health care products — Radiation — Part 1: Requirements for development,
validation and routine control of a sterilization process for medical devices
ISO 11137-2, Sterilization of health care products — Radiation — Part 2: Establishing the sterilization dose
ISO/TS 13004, Sterilization of health care products — Radiation — Substantiation of a selected sterilization
SD
dose: Method VD
max
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 11137-1, ISO 11137-2 and the
following apply.
3.1 Definitions
3.1.1
combined standard measurement uncertainty
standard measurement uncertainty that is obtained using the individual standard measurement uncertainties
associated with the input quantities in a measurement model. (VIM 2012)
3.1.2
coverage factor
number larger than one by which a combined standard measurement uncertainty is multiplied to obtain an
expanded measurement uncertainty
NOTE A coverage factor is usually symbolized k (see also GUM:1995, 2.3.6).
3.1.3
dose uniformity ratio
ratio of the maximum to the minimum absorbed dose within the irradiation container
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3.1.4
dosimetry system
interrelated elements used for determining absorbed dose, including dosimeters, instruments, associated
reference standards and procedures for their use [ISO/TS 11139:2006]
3.1.5
expanded measurement uncertainty
product of a combined standard measurement uncertainty and a factor larger than one
NOTE 1 The factor depends upon the type of probability distribution of the output quantity in a measurement model
and on the selected coverage probability.
NOTE 2 The term “factor” in this definition refers to a coverage factor.
3.1.6
scan length
dimension of the irradiation zone, perpendicular to the scan width and direction of the electron beam at a
specified distance from the accelerator window.
NOTE ASTM standards use "beam length" to mean the same thing that "scan length" means in this document. This
document uses "scan length" for consistency with ISO 11137-1.
3.1.7
scan width
dimension of the irradiation zone in the direction that the beam is scanned, perpendicular to the beam length
and direction of the electron beam at a specified distance from the accelerator window
NOTE ASTM standards use "beam width" to mean the same thing that "scan width" means in this document. This
document uses "scan width" for consistency with ISO 11137-1.
3.1.8
simulated product
material with attenuation and scattering properties similar to those of the product, material or substance to be
irradiated
NOTE 1 Simulated product is used as a substitute for the actual product, material or substance to be irradiated. When
used in routine production runs in order to compensate for the absence of product, simulated product is sometimes
referred to as compensating dummy. When used for absorbed dose mapping, simulated product is sometimes referred to
as phantom material.
NOTE 2 In this standard “dose mapping” is used for “absorbed dose mapping”
3.1.9
spatial resolution
resolution in two dimensions
NOTE Ability to detect change in dose in two dimensions
3.1.10
standard measurement uncertainty
uncertainty of the result of a measurement expressed as a standard deviation (VIM 2012)
3.1.11
uncertainty budget
statement of a measurement uncertainty, of the components of that measurement uncertainty, and of their
calculation and combination
NOTE An uncertainty budget should include the measurement model, estimates, and measurement uncertainties
associated with the quantities in the measurement model, covariances, type of applied probability density functions,
degrees of freedom, type of evaluation of measurement uncertainty, and any coverage factor.
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3.2 Terms
3.2.1 Dose specification(s)
3.2.1.1
D
max,acc
maximum acceptable dose determined in accordance with ISO 11137-1, section 8.1
3.2.1.2
D
ster
sterilization dose determined in accordance with ISO 11137-1, section 8.2
3.2.2 Doses
3.2.2.1
D
max
measured maximum dose in a given irradiation container
3.2.2.2
D
min
measured minimum dose in a given irradiation container
3.2.2.3
D
mon
measured dose at the routine monitoring position
3.2.3 Dose mapping ratios and their associated uncertainties
3.2.3.1
R
max/min
ratio of maximum to minimum dose (D /D ) determined by dose mapping
max min
3.2.3.2
R
max/mon
ratio of maximum to monitor dose (D /D ) determined by dose mapping
max mon
3.2.3.3
R
min/mon
ratio of minimum to monitor dose (D /D ) determined by dose mapping
min mon
3.2.4 Doses at monitoring positions that correlate to dose specifications
3.2.4.1
ster
D = D /R
mon ster min/mon
dose value at the monitoring location that directly correlates, by means of the ratio R , with D in product
min/mon ster
3.2.4.2
max,acc
D = D /R
mon max,acc max/mon
dose value at the monitoring location that directly correlates, by means of the ratio R , with D in
max/mon max,acc
product
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3.2.5 Dose targets
3.2.5.1
lower
D
target
calculated dose at the routine monitoring position used for establishing process control parameters that
ensure D is exceeded during routine processing.
ster
3.2.5.2
upper
D
target
calculated dose at the routine monitoring position used for establishing process control parameters that
ensure D is not exceeded during routine processing.
max,acc
3.2.6 Uncertainty
3.2.6.1
σ
total
calculated term that appropriately accounts for all potentially significant sources of measurement uncertainty
3.2.6.2
σ
cal
component of uncertainty associated with dosimetry system calibration
3.2.6.3
σ
map
component of uncertainty associated with dose mapping
3.2.6.4
σ
mach
component of uncertainty associated with machine variability
3.2.6.5
σ
rep
component of uncertainty associated with dose monitor measurement reproducibility
4 Measurement of Dose
4.1 All aspects of the dosimetry system(s) used have to comply with the relevant requirements of ISO
10012-1 or ISO 13485, which are normative references in ISO 11137-1.The dosimetry system(s) need to be
included in a formal measurement management system, as defined in ISO 10012-1, which sets out quality
procedures to achieve metrological confirmation and continual control of the measurement processes. An
important aspect of this is the competence and training of staff involved, both in the calibration and operation
of the dosimetry system(s), and also in the performance and analysis of dose measurements. Activities such
as the choice of location of dosimeters for dose mapping and the analysis of the resultant data require specific
skills and training. Examples of general requirements for dosimetry in radiation processing are given in
ISO/ASTM 52628 and further guidance on dose mapping can be found in ISO/ASTM 52303.
4.2 Measurement of absorbed dose in connection with the radiation sterilization of medical devices is
expressed in terms of absorbed dose to water. Dosimetry systems should be calibrated in terms of absorbed
dose to water.
NOTE In this part of ISO 11137, absorbed dose is referred to as dose.
4.3 With the completion of the calibration of the dosimetry system, establishment of measurement
traceability, and the application of the total measurement uncertainty to set process target values, the result of
a dosimeter measurement represents the best estimate of dose. Therefore, dose values from measured
dosimeters should not be corrected by the associated measurement uncertainty when determining if irradiated
product meets its dose specification.
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5 Measurement of dose to product
5.1 Dosimetry system selection and calibration
5.1.1 General
Dosimetry systems used in the development, validation and routine control of a radiation sterilization process
have to be capable of providing accurate and precise results over the entire dose range of interest and under
the conditions of use.
5.1.2 Selection of dosimetry systems
5.1.2.1 Dose measurements are required in the development, validation and routine control of radiation
sterilization; different dosimetry systems might be needed for these three different tasks. For example, in
sterilization dose establishment, the range of doses required for a verification or an incremental dose
experiment might be outside the calibrated range of the dosimetry system used for the measurement of
sterilization dose and, in such circumstances, an alternative system would have to be employed.
5.1.2.2 Guidance on the selection of appropriate dosimetry systems used in the development, validation
and routine control of radiation sterilization can be found in ISO/ASTM 52628. The properties of individual
dosimetry systems are given in ICRU 80. Procedures for their use are given in the ISO/ASTM Practices listed
in the Bibliography.
5.1.3 Calibration of dosimetry systems
5.1.3.1 Calibration of dosimetry systems for use in radiation sterilization is a significant activity. The
response of most dosimeters is influenced by the conditions of irradiation and measurement (e.g. temperature,
humidity, dose rate and interval of time between termination of irradiation and measurement). In addition, the
effects of these conditions are often interrelated and they can vary from batch to batch of dosimeters, see
ICRU 80 and ISO/ASTM 52701 for further details. Therefore, calibration should be carried out under
conditions that match as closely as possible the actual conditions of use. This means that calibrations or
calibration verifications might be needed for each irradiator pathway. It is inappropriate to apply the calibration
curve supplied by the dosimeter manufacturer without verification of its validity. However, the supplier’s curve
might provide useful information about the expected response of the dosimetry system. Where practicable, the
calibration should be based on irradiations carried out in the irradiator of intended use, rather than derived
from irradiations carried out at a different irradiator.
5.1.3.2 In order to ensure traceability of dose measurements, calibration irradiations and reference
standard dosimeters used as part of a calibration need to be supplied by a national metrology institute
recognized by the International Committee for Weights and Measures (CIPM) or other calibration laboratory
accredited to ISO/IEC 17025. A calibration certificate provided by a laboratory not having formal recognition
or accreditation might not necessarily be proof of traceability to a national or International Standard and
additional documentary evidence will be required.
5.1.3.3 The ability to make accurate dose measurements depends on the calibration and consiste
...
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