1、BSI Standards PublicationBS EN ISO 11135:2014Sterilization of health-careproducts Ethylene oxide Requirements for thedevelopment, validationand routine control of asterilization process for medicaldevicesBS EN ISO 11135:2014Incorporating corrigendum January 2015BS EN ISO 11135:2014 BRITISH STANDARDN
2、ational forewordThis British Standard is the UK implementation of EN ISO 11135:2014. It supersedes BS EN ISO 11135-1:2007 and DD CEN ISO/TS 11135-2:2008 which are withdrawn.The UK participation in its preparation was entrusted to Technical Committee CH/198, Sterilization of medical devices.A list of
3、 organizations represented on this 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 2015. Published by BSI Standards Limi
4、ted 2015ISBN 978 0 580 89221 9ICS 11.080.01Compliance 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 July 2014.Amendments/corrigenda issued since publicationDate Text a
5、ffected31 January 2015 Implementation of CEN Correction Notice 10 December 2014: the DOW has been corrected in the CEN ForewordEUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NORM EN ISO 11135 July 2014 ICS 11.080.01 Supersedes CEN ISO/TS 11135-2:2008, EN ISO 11135-1:2007English Version Sterilization o
6、f health-care products - Ethylene oxide - Requirements for the development, validation and routine control of a sterilization process for medical devices (ISO 11135:2014)Strilisation des produits de sant - Oxyde dthylne - Exigences de dveloppement, de validation et de contrle de routine dun processu
7、s de strilisation pour des dispositifs mdicaux (ISO 11135:2014) Sterilisation von Produkten fr die Gesundheitsfrsorge - Ethylenoxid - Anforderungen an die Entwicklung, Validierung und Lenkung der Anwendung eines Sterilisationsverfahrens fr Medizinprodukte (ISO 11135:2014) This European Standard was
8、approved by CEN on 28 June 2014. 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 nation
9、al 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 languag
10、e 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, H
11、ungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and United Kingdom. EUROPEAN COMMITTEE FOR STANDARDIZATION COMIT EUROPEN DE NORMALISATION EUROPISCHES KOMITEE FR NORMUNG CEN-C
12、ENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels 2014 CEN All rights of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO 11135:2014 EBS EN ISO 11135:2014EN ISO 11135:2014 (E)EN ISO 11135:2014 (E) 3 Foreword This document (EN ISO 11135:
13、2014) 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,
14、either by publication of an identical text or by endorsement, at the latest by January 2015, and conflicting national standards shall be withdrawn at the latest by July 2017. Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. CEN and
15、/or CENELEC shall not be held responsible for identifying any or all such patent rights. This document supersedes CEN ISO/TS 11135-2:2008, EN ISO 11135-1:2007. This document has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association, and support
16、s essential requirements of EU Directive(s). For relationship with EU Directive(s), see informative Annex ZA, ZB, which are integral parts of this document. According to the CEN-CENELEC Internal Regulations, the national standards organizations of the following countries are bound to implement this
17、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, Slovakia,
18、 Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom. Endorsement notice The text of ISO 11135:2014 has been approved by CEN as EN ISO 11135:2014 without any modification. BS EN ISO 11135:2014EN ISO 11135:2014 (E) 4 Annex ZA (informative) Relationship between this European Standard a
19、nd the Essential Requirements of EU Directive 90/385/EEC This European Standard has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association to provide one means of conforming to Essential Requirements of the New Approach Directive 90/385/EEC. Onc
20、e this standard is cited in the Official Journal of the European Union under that Directive and has been implemented as a national standard in at least one Member State, compliance with the clauses of this standard given in Table ZA.1 confers, within the limits of the scope of this standard, a presu
21、mption of conformity with the relevant Essential Requirements of that Directive and associated EFTA regulations. Table ZA.1 Correspondence between this European Standard and Directive 90/385/EEC Clauses of this EN Essential Requirements (ERs) of Directive 90/385/EEC Qualifying remarks/Notes 4,5,6,7,
22、8,9,10,11,12 7 This relevant Essential Requirement is only partly addressed in this European Standard. Packaging for maintenance of sterility during transportation and storage are not covered WARNING: Other requirements and other EU Directives may be applicable to the products falling within the sco
23、pe of this standard. BS EN ISO 11135:2014EN ISO 11135:2014 (E)BS EN ISO 11135:2014EN ISO 11135:2014 (E) 5 Annex ZB (informative) Relationship between this European Standard and the Essential Requirements of Directive 93/42/EEC This European Standard has been prepared under a mandate given to CEN by
24、the European Commission and the European Free Trade Association to provide one means of conforming to Essential Requirements of the New Approach Directive 93/42/EEC. Once this standard is cited in the Official Journal of the European Union under that Directive and has been implemented as a national
25、standard in at least one Member State, compliance with the clauses of this standard given in Table ZB.1 confers, within the limits of the scope of this standard, a presumption of conformity with the relevant Essential Requirements of that Directive and associated EFTA regulations. Table ZB.1 Corresp
26、ondence between this European Standard and Directive 93/42/EEC Clauses of this EN Essential Requirements (ERs) of Directive 90/42/EEC Qualifying remarks/Notes 4,5,6,7,8,9,10,11,12 8.3 This relevant Essential Requirement is only partly addressed in this European Standard. Packaging for maintenance of
27、 sterility during transportation and storage are not covered 4,5,6,7,8,9,10,11,12 8.4 WARNING: Other requirements and other EU Directives may be applicable to the products falling within the scope of this standard. BS EN ISO 11135:2014EN ISO 11135:2014 (E)BS EN ISO 11135:2014ISO 11135:2014(E) ISO 20
28、14 All rights reserved iiiContents PageForeword vIntroduction vi1 Scope . 11.1 Inclusions . 11.2 Exclusions 12 Normative references 23 Terms and definitions . 34 Quality management systems 114.1 Documentation 114.2 Management responsibility 114.3 Product realization . 114.4 Measurement, analysis and
29、 improvement Control of nonconforming product .115 Sterilizing agent characterization .115.1 General 115.2 Sterilizing agent 125.3 Microbicidal effectiveness 125.4 Material effects. 125.5 Safety and the environment 126 Process and equipment characterization 126.1 General 126.2 Process characterizati
30、on . 126.3 Equipment characterization . 137 Product definition 147.1 General 147.2 Product safety, quality and performance 157.3 Microbiological quality . 157.4 Documentation 158 Process definition .159 Validation 169.1 General 169.2 Installation qualification, IQ . 179.3 Operational qualification,
31、OQ 179.4 Performance qualification, PQ 189.5 Review and approval of validation . 2010 Routine monitoring and control .2211 Product release from sterilization 2312 Maintaining process effectiveness 2312.1 General 2312.2 Maintenance of equipment 2412.3 Requalification . 2412.4 Assessment of change 241
32、2.5 Assessment of equivalence 25Annex A (normative) Determination of lethal rate of the sterilization process Biological indicator/bioburden approach 26Annex B (normative) Conservative determination of lethal rate of the sterilization process Overkill approach .27Annex C (informative) Temperature se
33、nsors, RH sensors and biological indicator numbers 29BS EN ISO 11135:2014ISO 11135:2014(E)iv ISO 2014 All rights reservedAnnex D (informative) Guidance on the application of the normative requirements .32Annex E (normative) Single Lot Release 74Bibliography .76BS EN ISO 11135:2014ISO 11135:2014(E)Fo
34、rewordISO (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 tech
35、nical 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
36、 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
37、was drafted in accordance with the editorial rules of the ISO/IEC Directives, Part 2. www.iso.org/directivesAttention 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 r
38、ights. 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. www.iso.org/patentsAny trade name used in this document is information given for the convenience of users and does not constitute
39、an endorsement.For an explanation on the meaning of ISO specific terms and expressions related to conformity assessment, as well as information about ISOs adherence to the WTO principles in the Technical Barriers to Trade (TBT), see the following URL: Foreword - Supplementary informationThe committe
40、e responsible for this document is ISO/TC 198, Sterilization of health care products.ISO 11135:2014 cancels and replaces ISO 11135-1:2007 and ISO/TS 11135-2:2008, both of which have been technically revised and condensed into a single standard. ISO 2014 All rights reserved vBS EN ISO 11135:2014ISO 1
41、1135:2014(E)IntroductionA sterile medical device is one that is free of viable microorganisms. Medical devices produced under standard manufacturing conditions in accordance with the requirements for quality management systems (see for example ISO 13485) might, prior to sterilization, have microorga
42、nisms on them, albeit in low numbers. Such medical devices are non-sterile. The purpose of sterilization is to inactivate the microbiological contaminants and thereby transform the non-sterile medical devices into sterile ones.The kinetics of inactivation of a pure culture of microorganisms by physi
43、cal and/or chemical agents used to sterilize medical devices can generally best be described by an exponential relationship between the numbers of microorganisms surviving and the extent of treatment with the ethylene oxide (EO); inevitably this means that there is always a finite probability that a
44、 microorganism might survive regardless of the extent of treatment applied. For a given treatment, the probability of survival is determined by the number and resistance of microorganisms and by the environment in which the organisms exist during treatment. It follows that the sterility of any one m
45、edical device in a population subjected to sterilization processing cannot be guaranteed and the sterility of a processed population is defined in terms of the probability of there being a viable microorganism present on a medical device.ISO 11135 describes requirements that, if met, will provide an
46、 ethylene oxide sterilization process intended to sterilize medical devices, which has appropriate microbicidal activity. Furthermore, compliance with the requirements ensures that validations conducted following this International Standard will provide products that meet the defined requirements fo
47、r sterile products with a high degree of confidence. The specification for this probability is a matter for regulatory authorities and can vary from country to country (see for example EN 556-1 and ANSI/AAMI ST67).Generic requirements of the quality management systems for design and development, pro
48、duction, installation and servicing are given in ISO 9001 and particular requirements for quality management systems for medical device production are given in ISO 13485. The standards for quality management systems recognize that, for certain processes used in manufacturing or reprocessing, the eff
49、ectiveness of the process cannot be fully verified by subsequent inspection and testing of the product. Sterilization is an example of such a process. For this reason, sterilization processes are validated for use, the performance of the sterilization process monitored routinely and the equipment maintained.Exposure to a properly validated, accurately controlled sterilization process is not the only factor associated with the provision of reliable assurance that the product is sterile and, in this regard, suitable for its intended use. Attention
