1、Sterilization of health care products - RadiationPart 3: Guidance on dosimetric aspects of development, validation and routine controlBS EN ISO 11137-3:2017BSI Standards PublicationWB11885_BSI_StandardCovs_2013_AW.indd 1 15/05/2013 15:06National forewordThis British Standard is the UK implementation
2、 of EN ISO 11137-3:2017. It is identical to ISO 11137-3:2017. It supersedes BS EN ISO 11137-3:2006, which is withdrawn.The UK participation in its preparation was entrusted to Technical Committee CH/198, Sterilization and Associated Equipment and Processes.A list of organizations represented on this
3、 committee can be obtained on request to its secretary.This publication does not purport to include all the necessary provisions of a contract. Users are responsible for its correct application. The British Standards Institution 2017 Published by BSI Standards Limited 2017ISBN 978 0 580 82896 6ICS 1
4、1.080.01Compliance with a British Standard cannot confer immunity from legal obligations. This British Standard was published under the authority of the Standards Policy and Strategy Committee on 31 August 2017.Amendments/corrigenda issued since publicationDate Text affected BRITISH STANDARDBS EN IS
5、O 11137-3:2017EUROPEAN STANDARDNORME EUROPENNEEUROPISCHE NORMEN ISO 11137-3July 2017ICS 11.080.01 Supersedes EN ISO 11137-3:2006EUROPEAN COMMITTEE FOR STANDARDIZATIONCOMIT EUROPEN DE NORMALISATIONEUROPISCHES KOMITEE FR NORMUNGCEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels 2017 CEN
6、Ref. No. EN ISO 11137-3:2017: EAll rights of exploitation in any form and by any means reserved worldwide for CEN national MembersSterilization of health care products - Radiation - Part 3: Guidance on dosimetric aspects of development, validation and routine control (ISO 11137-3:2017)Strilisation d
7、es produits de sant - Irradiation - Partie 3: Directives relatives aux aspects dosimtriques de dveloppement, la validation et le contrle de routine (ISO 11137-3:2017)Sterilisation von Produkten fr die Gesundheitsfrsorge - Strahlen - Teil 3: Anleitung zu dosimetrischen Aspekten der Entwicklung, Valid
8、ierung 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 alte
9、ration. 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
10、 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
11、, 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.English VersionEN ISO 1
12、1137-3:2017 (E)European forewordThis 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 Europea
13、n 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
14、 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
15、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, Port
16、ugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom.Endorsement noticeThe text of ISO 11137-3:2017 has been approved by CEN as EN ISO 11137-3:2017 without any modification.iiBS EN ISO 11137-3:2017ISO 11137-3:2017(E)Foreword vIntroduction vi1 Scope . 1
17、2 Normative references 13 Terms, definitions and symbols 13.1 General . 13.2 Symbols . 34 Measurement of dose. 44.1 General . 44.1.1 Direct and indirect dose measurements . 44.1.2 Dosimetry systems . 44.1.3 Best estimate of dose . 44.2 Dosimetry system selection and calibration . 54.2.1 General 54.2
18、.2 Selection of dosimetry systems . 54.2.3 Calibration of dosimetry systems 54.3 Dose measurement uncertainty . 64.3.1 General concepts 64.3.2 The Guide to the expression of uncertainty in measurement (GUM) methodology 64.3.3 Radiation sterilization specific aspects of dose measurement uncertainty .
19、 75 Establishing the maximum acceptable dose 86 Establishing the sterilization dose 97 Installation qualification 108 Operational qualification .118.1 General 118.2 Gamma irradiators 118.3 Electron beam irradiators 138.4 X-ray irradiators 159 Performance qualification 179.1 General 179.2 Gamma irrad
20、iators 189.2.1 Loading pattern .189.2.2 Dosimetry 199.2.3 Analysis of dose mapping data . 209.3 Electron beam irradiators 209.3.1 Loading pattern .209.3.2 Dosimetry 229.3.3 Analysis of dose mapping data . 229.4 X-ray irradiators 239.4.1 Loading pattern .239.4.2 Dosimetry 249.4.3 Analysis of dose map
21、ping data . 2510 Routine monitoring and control .2510.1 General 2510.2 Frequency of dose measurements 26Annex A (informative) Mathematical modelling .27Annex B (informative) Tables of references for dosimetry-related testing during IQ/OQ/PQ .30 ISO 2017 All rights reserved iiiContents PageBS EN ISO
22、11137-3:2017ISO 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 .33Annex D (informative) Application of dose measurement uncertainty in setting process target doses .34Bibliography .40iv ISO 2017
23、All rights reservedBS EN ISO 11137-3:2017ISO 11137-3:2017(E)ForewordISO (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 committ
24、ees. 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 Int
25、ernational 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 di
26、fferent 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 sh
27、all 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
28、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 ISOs adherence to the World Trade Organiz
29、ation (WTO) principles in the Technical Barriers to Trade (TBT) see the following URL: www.iso.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 ), whi
30、ch 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 vBS EN ISO 11137-3:2017ISO 11137-3:2017(E)IntroductionAn integral part of radiation sterilization is the ability to measure dose. Dose is measured during all stag
31、es 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 environm
32、ental 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 t
33、he 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 explanation
34、s 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 reservedB
35、S EN ISO 11137-3:2017Sterilization of health care products - Radiation Part 3: Guidance on dosimetric aspects of development, validation and routine control1 ScopeThis 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
36、 use in development, validation and routine control of a radiation sterilization process.2 Normative referencesThe 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 a
37、pplies. 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 devicesISO 11137-
38、2 , Sterilization of health care products Radiation Part 2: Establishing the sterilization doseISO/TS 13004 , Sterilization of health care products Radiation Substantiation of a selected sterilization dose: Method VDmaxSDISO 13485 , Medical devices Quality management systems Requirements for regulat
39、ory purposes3 Terms, definitions and symbolsFor 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 ht
40、tp:/www.electropedia.org/ ISO Online browsing platform: available at http:/www.iso.org/obp 3.1 General3.1.1absorbed dosedosequantity of ionizing radiation energy imparted per unit mass of a specified materialSOURCE: ISO 11137-1:2006, 3.1, modifiedNote 1 to entry: For the purposes of this document, t
41、he term “dose” is used to mean “absorbed dose”.INTERNATIONAL STANDARD ISO 11137-3:2017(E) ISO 2017 All rights reserved 1BS EN ISO 11137-3:2017ISO 11137-3:2017(E)3.1.2combined standard measurement uncertaintystandard measurement uncertainty (3.1.13) that is obtained using the individual standard meas
42、urement uncertainties associated with the input quantities in a measurement modelSOURCE: VIM 2012, 2.313.1.3coverage factornumber 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 covera
43、ge factor is usually symbolized as “k” (see also the GUM:1995, 2.3.6).3.1.4direct dose measurementmeasurement of absorbed dose (3.1.1) with a dosimeter at the location of interestNote 1 to entry: For example, a direct measurement of minimum dose is made with a dosimeter at the minimum dose location
44、in an irradiation container.3.1.5dose uniformity ratioratio of the maximum to the minimum absorbed dose (3.1.1) within the irradiation container3.1.6dosimetry systeminterrelated elements used for determining absorbed dose (3.1.1), including dosimeters, instruments, associated reference standards and
45、 procedures for their useSOURCE: ISO/TS 11139:2006, 2.153.1.7expanded measurement uncertaintyproduct of a combined standard measurement uncertainty (3.1.2) and a factor larger than the number oneNote 1 to entry: The factor depends on the type of probability distribution of the output quantity in a m
46、easurement model and on the selected coverage probability.Note 2 to entry: The term “factor” in this definition refers to a coverage factor.3.1.8indirect dose measurementmeasurement of absorbed dose (3.1.1) at a location remote from a directly measured dosimeter, calculated by the application of fac
47、torsNote 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.3.1.9scan lengthdimension of the irradiation zone, pe
48、rpendicular to the scan width and direction of the electron beam at a specified distance from the accelerator windowNote 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-
49、1 .2 ISO 2017 All rights reservedBS EN ISO 11137-3:2017ISO 11137-3:2017(E)3.1.10scan widthdimension 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 windowNote 1 to entry: ISO/ASTM standards use “beam width” to mean the same thing that “scan width” means in this document.3.1.11simulated productmaterial with attenuation and scattering properties similar to those of the product, material or substance
