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

Status
Published
Public Enquiry End Date
29-Sep-2015
Publication Date
11-Sep-2017
Technical Committee
Current Stage
6060 - National Implementation/Publication (Adopted Project)
Start Date
23-Aug-2017
Due Date
28-Oct-2017
Completion Date
12-Sep-2017

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SLOVENSKI STANDARD
SIST EN ISO 11137-3:2017
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
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

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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.
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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
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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
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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

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-
max,acc
ance with ISO 11137-1:2006, 8.1
sterilization dose determined in accordance with
ster
ISO 11137-1:2006, 8.2
direct measurement of maximum dose in a given
max
irradiation container
direct measurement of minimum dose in a given
min
irradiation container
direct measurement of dose at the routine monitor-
mon
ing position
ratio of maximum to minimum dose (D /D )
max min
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
max/mon
determined by dose mapping
ratio of minimum to monitor dose (D /D )
min mon
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
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
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
...

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