SIST EN ISO 11137-3:2017

SLOVENSKI STANDARD
01-oktober-2017
1DGRPHãþD
SIST EN ISO 11137-3:2006
6WHULOL]DFLMDL]GHONRY]D]GUDYVWYHQRQHJR6HYDQMHGHO6PHUQLFHR
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
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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.

Contents Page
European foreword . 3

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.
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
ISO 11137-3:2017(E)
© 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

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 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

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 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

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 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

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 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 mapping can be found in Reference [18].
Measurements of absorbed dose in connection with the radiation sterilization of health care products
are expressed in terms of absorbed dose to water and, therefore, dosimetry systems should be
calibrated in terms of absorbed dose to water.
4.1.3 Best estimate of dose
With the completion of the calibration of the dosimetry system and establishment of measurement
traceability (see 4.2.3), the result of each dose measurement, direct and indirect, represents the best
estimate of dose.
4 © ISO 2017 – All rights reserved

ISO 11137-3:2017(E)
Values from dose measurements should not be corrected by applying associated measurement
uncertainty.
4.2 Dosimetry system selection and calibration
4.2.1 General
Dosimetry systems used in the development, validation and routine control of a radiation sterilization
process should be capable of providing accurate and precise measurements over the entire dose range
of interest and under the conditions of use.
4.2.2 Selection of dosimetry systems
4.2.2.1 Direct 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 dose in routine processing and, in such circumstances, a different system would have to
be employed.
4.2.2.2 Guidance on the selection of appropriate dosimetry systems used in the development,
[19]
validation and routine control of radiation sterilization can be found in ISO/ASTM 52628 . The
properties of individual dosimetry systems are given in Reference [28]. Procedures for their use are
given in the ISO/ASTM Practices listed in the References [5], [7] to [11], [13] and [15].
4.2.3 Calibration of dosimetry systems
4.2.3.1 Calibration of dosimetry systems for use in radiation sterilization is a significant activity. The
response of most dosimeters is influenced by one or more of the conditions of irradiation and measurement
(e.g. temperature, humidity, exposure to light, dose rate and interval of time between termination of
irradiation and measurement). In addition, the effects of these conditions are often interrelated and
[28] [20]
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.
4.2.3.2 In order to ensure traceability of dose measurements, calibration irradiations and reference
standard dosimeters used as part of a calibration should be supplied by a national metrology institute
recognized by the International Committee for Weights and Measures (CIPM) or other calibration
laboratory in accordance with 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
an International Standard and additional documentary evidence will be required (see ISO/ASTM 51261).
4.2.3.3 The ability to make accurate direct dose measurements depends on the calibration and
consistency of performance of the entire dosimetry system. This means that all of the equipment
associated with the measurement procedure, not just the dosimeters, should be controlled and calibrated
or, if equipment cannot be calibrated, its performance should be verified.
4.2.3.4 It is important that the validity of the calibration is maintained throughout the period of use
of the calibration results. This might entail performing verification of the calibration using a reference
dosimetry system (see ISO/ASTM 52628) at regular intervals and also when a significant change in
ISO 11137-3:2017(E)
irradiation conditions has occurred, for example, following source replenishment. Seasonal variations in
temperature and humidity can potentially affect dosimeter response. A periodic assessment to quantify
these variations and their effect, if any, on dosimeter response should be carried out and a calibration
verification exercise carried out if necessary.
4.2.3.5 The response of some types of dosimeters is known to be influenced by the period of time
between termination of irradiation and measurement. The magnitude of this effect can depend on storage
conditions during this period and the manufacturer’s recommendations on storage should be followed,
particularly regarding temperature, humidity and exposure to light. The effect of storage conditions
should be taken into account when determining the acceptable time interval between termination of
irradiation and measurement of the dosimeters and when interpreting dose measurements. For more
information on factors that can influence dosimeter response, see ISO/ASTM 52701.
4.2.3.6 Detailed calibration procedures are given in ISO/ASTM 51261. Information on estimating and
reporting uncertainty of dose measurement can be found in ISO/ASTM 51707. Additional guidance is
given in Reference [30].
As discussed in ISO/ASTM 51261, the estimate of uncertainty should take into account the differences
between calibration and routine processing, e.g. differences in influence quantities such as irradiation
temperature or absorbed dose rate, or differences in measurement practices such as use of average
versus individual value for dosimeter thickness or background absorbance.
4.3 Dose measurement uncertainty
4.3.1 General concepts
It is a requirement in ISO 11137-1 that dose measurements are traceable to an appropriate national or
International Standard and that the level of uncertainty of the measurements is known. Consequently, all
potentially significant sources of measurement uncertainty should be identified and their magnitudes
assessed. However, depending on the method chosen for quantifying measurement uncertainty, it may
be possible to determine the magnitudes of combinations of components of uncertainty, rather than
quantifying each component individually.
All measurements, direct and indirect, need to have an estimate of uncertainty that indicates the degree
of knowledge associated with the measurement (i.e. the quality of the measurement). When a quantity,
such as absorbed dose, is measured, the result depends on multiple factors, such as the dosimetry
system, the skill of the operator or the measurement environment. Even if the same dosimeter is
measured several times on the same instrument, there will be a spread of results characteristic of the
dosimetry system.
4.3.2 The Guide to the expression of uncertainty in measurement (GUM) methodology
4.3.2.1 In the context of measurement uncertainty, this document follows the methodology and
terminology described in Reference [26].
4.3.2.2 A dose measurement can be considered to be an estimate of the true value of the absorbed
dose. In the case of a well-defined and controlled measurement process, the measurement result will
be the best estimate of the value of the absorbed dose (4.1.3). However, the uncertainty inherent in the
measurement means that there will be a finite probability that the true value will actually lie above or
below the measurement result.
4.3.2.3 In many cases, the probability of the true value being above or below the measurement result
will follow a Gaussian, or “normal”, distribution. The peak of the distribution represents the measured
(best estimate) value, with values above and below this becoming progressively less likely at increasing
distances from the measurement result. The width of the Gaussian distribution is characterised by a
parameter known as the standard uncertainty (or standard deviation), given the symbol σ (sigma).
6 © ISO 2017 – All rights reserved

ISO 11137-3:2017(E)
NOTE There are many different types of probability distributions that might appropriately characterize
individual components of uncertainty. However, in order to mathematically combine these individual components
to estimate the total uncertainty in the dose measurement, it is necessary that they be presented in the same
form, for example relative standard deviation. Refer to the GUM and ISO/ASTM 51707 for additional information
on probability distributions and combining components of uncertainty.
4.3.2.4 A convenient way to express measurement uncertainty is by a confidence interval or
coverage interval, which represents the range within which the true value of the quantity is likely to
lie. The confidence interval has to be based on a stated level of confidence that the true value will be
within the range.
4.3.2.5 A common way to express a measurement result is in the form x ± y, where x is the measured or
calculated (best estimate) value and y is the standard measurement uncertainty multiplied by a coverage
factor (k). A standard measurement uncertainty multiplied by a coverage factor is known as an “expanded
measurement uncertainty”. According to the GUM, the value of the coverage factor used must be stated. A
coverage factor of 2 is commonly used, corresponding to a level of confidence of approximately 95 %.
NOTE The exact relationship between the level of confidence and expanded measurement uncertainty
depends on the number of degrees of freedom associated with the measurement (see the GUM for further
information).
4.3.2.6 In order to establish the uncertainty associated with a measurement of dose, it is necessary to
first identify all potentially significant sources of uncertainty and then quantify them either individually
or in combination. This is most readily done by considering, in turn, each step involved in the calibration
and use of a dosimetry system and assessing what uncertainties are likely to be associated with each of
these steps. The procedure used in the GUM is to ascribe to each component of uncertainty an effective
standard deviation, known as a “standard uncertainty”, and to combine these standard uncertainties
to produce an estimate of overall uncertainty. This method allows both random and systematic
influences to be combined to produce an overall estimate of uncertainty that represents the quality of
the measurement. A tabulation of the individual components of uncertainty, along with their values and
methods of estimation, is often referred to as an “uncertainty budget”. Detailed descriptions of how to
[16] [30]
carry out this process are given in, for example, ISO/ASTM 51707 and CIRM 29 .
4.3.3 Radiation sterilization specific aspects of dose measurement uncertainty
4.3.3.1 For dose measurements in radiation sterilization processing, the measurement uncertainty
that has to be considered is the uncertainty associated with the direct measurement of dose or with
the estimate of the value of dose received by product in an irradiation container through an indirect
measurement (4.1.1).
4.3.3.2 Dose received by product in an irradiation container is measured directly during dose mapping
exercises, but this is not always the case during routine radiation processing. Radiation processes
may be monitored directly by dose measurement at positions of minimum and maximum doses or at
positions remote from those locations. When not monitoring at the minimum and maximum locations,
direct measurements at the remote monitoring location need to be multiplied by factors to account for
dose differences between the dose at the monitoring dosimeter position and those at the position of
minimum and maximum dose in an irradiation container. These factors are expressed as dose ratios, e.g.
R and R , and are experimentally determined in dose mapping exercises and are subject to
min/mon max/mon
uncertainty. The ratios can directly correlate product specification doses (D and D ) to specific
ster max,acc
ster max,acc
dose values (D and D ) at the monitoring position (see 3.2):
mon mon
ster
D = D /R (1)
mon ster min/mon
max,acc
D = D /R (2)
mon max,acc max/mon
ISO 11137-3:2017(E)
4.3.3.3 The uncertainty components associated with direct or indirect measurement of dose in an
irradiation container can be subdivided as given below:
— the uncertainty reported by the calibration standards laboratory;
— the uncertainty due to mathematical fitting of the calibration function;
— the uncertainty related to the effect of environmental influence quantities on dosimeters during
calibration and use;
— the uncertainty related to the reproducibility of the monitoring dosimeter;
— the uncertainty, for indirect measurements, in dose ratios derived from dose mapping;
— the uncertainty, if applicable, for indirect measurements, arising from variations in irradiator dose
delivery between the irradiation of the monitoring dosimeter and the irradiation of the container in
which it is required to estimate the dose.
The items on this list should be considered in establishing an uncertainty budget but may not be
applicable to all processes; they are not intended to be a checklist. Depending on the method chosen for
quantifying measurement uncertainty, it may be possible to determine the magnitudes of combinations
of components of uncertainty, rather than quantifying each component individually.
lower upper
Uncertainty values can be used to determine process target dose values (D and D )
target target
ster
that are higher than D (or D if the process is not monitored at the minimum dose location)
ster mon
max,acc
and lower than D (or D if the process is not monitored at the maximum acceptable
max,acc mon
dose location). One method for determining process target values is to use values of the product kσ to
calculate process target doses, where σ is a standard uncertainty derived from a combination of those
components given above that are applicable to the specific situation. The value of k is dependent on
the required lev
...