1、 g49g50g3g38g50g51g60g44g49g42g3g58g44g55g43g50g56g55g3g37g54g44g3g51g40g53g48g44g54g54g44g50g49g3g40g59g38g40g51g55g3g36g54g3g51g40g53g48g44g55g55g40g39g3g37g60g3g38g50g51g60g53g44g42g43g55g3g47g36g58Part 1: Requirements for the development, validation and routine control of a sterilization process
2、 for medical devicesThe European Standard EN ISO 17665-1:2006 has the status of a British StandardICS 11.080.01Sterilization of health care products Moist heat BRITISH STANDARDBS EN ISO 17665-1:2006BS EN ISO 17665-1:2006This British Standard was published under the authority of the Standards Policy
3、and Strategy Committee on 29 September 2006 BSI 2006ISBN 0 580 48982 5Amendments issued since publicationAmd. No. Date Commentscontract. Users are responsible for its correct application.Compliance with a British Standard cannot confer immunity from legal obligations.National forewordThis British St
4、andard was published by BSI. It is the UK implementation of EN ISO 17665-1:2006. It supersedes BS EN 554:1994 which is withdrawn.The UK participation in its preparation was entrusted to Technical Committee CH/198, Sterilization of medical devices.A list of organizations represented on CH/198 can be
5、obtained on request to its secretary.This publication does not purport to include all the necessary provisions of a EUROPEAN STANDARDNORME EUROPENNEEUROPISCHE NORMEN ISO 17665-1August 2006ICS 11.080.01 Supersedes EN 554:1994 English VersionSterilization of health care products - Moist heat - Part 1:
6、Requirements for the development, validation and routinecontrol of a sterilization process for medical devices (ISO 17665-1:2006)Strilisation des produits de sant - Chaleur humide -Partie 1: Exigences pour le dveloppement, la validation etle contrle de routine dun procd de strilisation desdispositif
7、s mdicaux (ISO 17665-1:2006)Sterilisation von Produkten fr die Gesundheitsfrsorge -Feuchte Hitze - Teil 1: Anforderungen an die Entwicklung,Validierung und Lenkung der Anwendung einesSterilisationsverfahrens fr Medizinprodukte (ISO 17665-1:2006)This European Standard was approved by CEN on 14 July 2
8、006.CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this EuropeanStandard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such nationalstandards may be obtained on
9、 application to the Central Secretariat or to any CEN member.This European Standard exists in three official versions (English, French, German). A version in any other language made by translationunder the responsibility of a CEN member into its own language and notified to the Central Secretariat h
10、as the same status as the officialversions.CEN members are the national standards bodies of Austria, Belgium, Cyprus, Czech Republic, Denmark, Estonia, Finland, France,Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Roma
11、nia,Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.EUROPEAN COMMITTEE FOR STANDARDIZATIONCOMIT EUROPEN DE NORMALISATIONEUROPISCHES KOMITEE FR NORMUNGManagement Centre: rue de Stassart, 36 B-1050 Brussels 2006 CEN All rights of exploitation in any form and by any means reservedworl
12、dwide for CEN national Members.Ref. No. EN ISO 17665-1:2006: EForeword This document (EN ISO 17665-1:2006) 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 secretar
13、iat 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 February 2007, and conflicting national standards shall be withdrawn at the latest by August 2009. This document supers
14、edes EN 554:1994. This document has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association, and supports essential requirements of EU Directive(s). For relationship with EU Directive(s), see informative Annex ZA, which is an integral part of thi
15、s document. According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy
16、, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom. Endorsement notice The text of ISO 17665-1:2006 has been approved by CEN as EN ISO 17665-1:2006 without any modifications. EN ISO 17665-1:2006Ref
17、erence numberISO 17665-1:2006(E)INTERNATIONAL STANDARD ISO17665-1First edition2006-08-15Sterilization of health care products Moist heat Part 1: Requirements for the development, validation and routine control of a sterilization process for medical devices Strilisation des produits de sant Chaleur h
18、umide Partie 1: Exigences pour le dveloppement, la validation et le contrle de routine dun procd de strilisation des dispositifs mdicaux EN ISO 17665-1:2006ii iiiContents Page Foreword. v Introduction . vi 1 Scope . 1 1.1 Inclusions 1 1.2 Exclusions . 1 2 Normative references . 2 3 Terms and definit
19、ions. 3 4 Quality management system elements 10 4.1 Documentation 10 4.2 Management responsibility . 10 4.3 Product realization 10 4.4 Measurement, analysis and improvement Control of non-conforming product . 10 5 Sterilizing agent characterization . 11 5.1 Sterilizing agent 11 5.2 Microbicidal effe
20、ctiveness . 11 5.3 Materials effects 11 5.4 Environmental consideration 11 6 Process and equipment characterization 11 6.1 Process 11 6.1.1 General. 11 6.1.2 Saturated steam processes . 12 6.1.3 Contained product processes . 12 6.2 Equipment . 13 7 Product definition . 14 8 Process definition. 15 9
21、Validation. 17 9.1 General. 17 9.2 Installation qualification (IQ) . 17 9.2.1 Equipment . 17 9.2.2 Installation . 17 9.2.3 Function. 17 9.3 Operational qualification (OQ). 18 9.4 Performance qualification (PQ) . 18 9.5 Review and approval of validation 19 10 Routine monitoring and control 20 11 Prod
22、uct release from sterilization. 21 12 Maintaining process effectiveness . 21 12.1 Demonstration of continued effectiveness 21 12.2 Recalibration . 21 12.3 Maintenance of equipment 21 12.4 Requalification 22 12.5 Assessment of change. 22 Annex A (informative) Guidance. 23 Annex B (informative) Proces
23、s definition based on inactivation of the microbial population in its natural state (bioburden-based method)27 EN ISO 17665-1:2006iv Annex C (informative) Process definition based on the inactivation of a reference microorganism and a knowledge of bioburden on product items to be sterilized (combine
24、d bioburden/biological indicator based method) 28 Annex D (informative) Conservative process definition based on inactivation of reference microorganisms (overkill method) 29 Annex E (informative) Operating cycles. 31 Bibliography . 36 EN ISO 17665-1:2006Annex ZA (informative) Relationship between t
25、his European Standard and the Essential Requirements of EU Directive 90/385/EEC, 93/42/EEC and 98/79/EEC 39 vForeword ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO member bodies). The work of preparing International Standards is
26、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
27、in the work. ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization. International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2. The main task of technical committees is to pre
28、pare International Standards. Draft International Standards adopted by the technical committees are circulated to the member bodies for voting. Publication as an International Standard requires approval by at least 75 % of the member bodies casting a vote. Attention is drawn to the possibility that
29、some of the elements of this document may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. ISO 17665-1 was prepared by Technical Committee ISO/TC 198, Sterilization of health care products. This first edition of ISO 17665-1 cancels and
30、 replaces ISO 11134:1994 and ISO 13683:1997 both of which have been technically revised. ISO 17665 consists of the following parts, under the general title Sterilization of health care products Moist heat: Part 1: Requirements for the development, validation and routine control of a sterilization pr
31、ocess for medical devices Part 2: Guidance on the application of ISO 17665-1 EN ISO 17665-1:2006vi Introduction A sterile medical device is one which is free of viable microorganisms. International standards that specify requirements for validation and routine control of sterilization processes requ
32、ire, when it is necessary to supply a sterile medical device, that adventitious microbiological contamination of a medical device prior to sterilization be minimized. Even so, medical devices produced under standard manufacturing conditions in accordance with the requirements for quality management
33、systems (see, for example, ISO 13485) may, prior to sterilization, have microorganisms on them, albeit in low numbers. Such products are non-sterile. The purpose of sterilization is to inactivate the microbiological contaminants and thereby transform the non-sterile products into sterile ones. The k
34、inetics of inactivation of a pure culture of microorganisms by physical and/or chemical agents used to sterilize medical devices generally can best be described by an exponential relationship between the number of microorganisms surviving and the extent of treatment with the sterilizing agent; inevi
35、tably this means that there is always a finite probability that a microorganism may 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 exi
36、st during treatment. It follows that the sterility of any one product 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 product item. ISO 176
37、65 describes requirements that, if met, will provide a moist heat sterilization process intended to sterilize medical devices, which has appropriate microbicidal activity. Furthermore, compliance with the requirements ensures this activity is both reliable and reproducible so that predictions can be
38、 made, with reasonable confidence, that there is a low level of probability of there being a viable microorganism present on product after sterilization. Specification of this probability is a matter for regulatory authorities and may vary from country to country (see, for example, EN 556-1 and ANSI
39、/AAMI ST67). Generic requirements of the quality management system for design and development, production, 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 manag
40、ement systems recognise that, for certain processes used in manufacturing, the effectiveness 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
41、 performance of the sterilization process is monitored routinely and the equipment is 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,
42、suitable for its intended use. Attention is therefore given to a number of factors including: a) the microbiological status of incoming raw materials and/or components; b) the validation and routine control of any cleaning and disinfection procedures used on the product; c) the control of the enviro
43、nment in which the product is manufactured, assembled and packaged; d) the control of equipment and processes; e) the control of personnel and their hygiene; f) the manner and materials in which the product is packaged; g) the conditions under which product is stored. EN ISO 17665-1:2006viiThe type
44、of contamination on a product to be sterilized varies and this has an impact upon the effectiveness of a sterilization process. It is preferable that products that have been used in a health care setting and that are being presented for resterilization in accordance with the manufacturers instructio
45、ns (see ISO 17664) be regarded as special cases. There is the potential for such products to possess a wide range of contaminating microorganisms and residual inorganic and/or organic contamination in spite of the application of a cleaning process. Hence, particular attention has to be given to the
46、validation and control of the cleaning and disinfection processes used during reprocessing. This part of ISO 17665 describes the requirements for ensuring that the activities associated with the process of moist heat sterilization are performed properly. These activities are described in documented
47、work programmes designed to demonstrate that the moist heat sterilization process will consistently yield sterile products on treatment with process variables falling within the predetermined limits. The requirements are the normative parts of this part of ISO 17665 with which compliance is claimed.
48、 The guidance given in the informative annexes 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, i
49、f they are effective in achieving compliance with the requirements of this part of ISO 17665. The development, validation and routine control of a sterilization process comprise a number of discrete but interrelated activities, e.g. calibration, maintenance, product definition, process definition, installation qualification, operational qualification and performance qualification. While the activities required by this part of ISO 17665 have been grouped together and are presented in a particular order,
