1、November 2015 English price group 28No part of this translation may be reproduced without prior permission ofDIN Deutsches Institut fr Normung e. V., Berlin. Beuth Verlag GmbH, 10772 Berlin, Germany,has the exclusive right of sale for German Standards (DIN-Normen).ICS 11.080.99!%GR9“2364722www.din.d
2、eDIN EN ISO 11137-2Sterilization of health care products Radiation Part 2: Establishing the sterilization dose (ISO 11137-2:2013);English version EN ISO 11137-2:2015,English translation of DIN EN ISO 11137-2:2015-11Sterilisation von Produkten fr die Gesundheitsfrsorge Strahlen Teil 2: Festlegung der
3、 Sterilisationsdosis (ISO 11137-2:2013);Englische Fassung EN ISO 11137-2:2015,Englische bersetzung von DIN EN ISO 11137-2:2015-11Strilisation des produits de sant Irradiation Partie 2: tablissement de la dose strilisante (ISO 11137-2:2013);Version anglaise EN ISO 11137-2:2015,Traduction anglaise de
4、DIN EN ISO 11137-2:2015-11SupersedesDIN EN ISO 11137-2:2013-09www.beuth.deDocument comprises 81 pagesDTranslation by DIN-Sprachendienst.In case of doubt, the German-language original shall be considered authoritative.10.15 DIN EN ISO 11137-2:2015-11 2 A comma is used as the decimal marker. National
5、foreword This document (EN ISO 11137-2:2015) has been prepared by Technical Committee ISO/TC 198 “Sterilization of health care products” in collaboration with Technical Committee CEN/TC 204 “Sterilizers for medical purposes” (Secretariat: BSI, United Kingdom). The responsible German body involved in
6、 its preparation was DIN-Normenausschuss Medizin (DIN Standards Committee Medical ), Working Committee NA 063-01-07 AA Sterilisation von Medizinprodukten. According to Resolution CEN/BT C52/2015 Annexes ZA, ZB and ZC and the European Foreword have been updated and published in June 2015 as a new edi
7、tion of EN ISO 11137-2:2015. Thus, this new edition of DIN EN ISO 11137-2 has also been published. This document contains ISO 11137-2:2013, unchanged. DIN EN ISO 11137 consists of the following parts, under the general title Sterilization of health care products Radiation: Part 1: Requirements for d
8、evelopment, validation and routine control of a sterilization process for medical devices Part 2: Establishing the sterilization dose Part 3: Guidance on dosimetric aspects The DIN Standards corresponding to the International Standards referred to in this document are as follows: ISO 11137-1 DIN EN
9、ISO 11137-1 ISO 11137-3 DIN EN ISO 11137-3 ISO 11737-1 DIN EN ISO 11737-1 ISO 11737-2 DIN EN ISO 11737-2 ISO 13485 DIN EN ISO 13485 ISO 14971 DIN EN ISO 14971 Amendments This standard differs from DIN EN ISO 11137-2:2013-09 as follows: a) the European foreword has been updated; b) Annex ZA (informat
10、ive) “Relationship between this European Standard and the Essential Requirements of EU Directive 90/385/EEC on active implantable medical devices” has been updated; c) Annex ZB (informative) “Relationship between this European Standard and the Essential Requirements of EU Directive 93/42/EEC on medi
11、cal devices” has been updated; d) Annex ZC (informative) “Relationship between this European Standard and the Essential Requirements of EU Directive 98/79/EEC on in vitro diagnostic medical devices” has been updated. DIN EN ISO 11137-2:2015-11 3 Previous editions DIN EN 552: 1994-11, 2001-02 DIN EN
12、552 Corrigendum 1: 1999-07 DIN EN ISO 11137-2: 2006-07, 2007-09, 2012-07, 2013-09 DIN EN ISO 11137-2 Corrigendum 1: 2009-09 DIN EN ISO 11137-2:2015-11 4 National Annex NA (informative) Bibliography DIN EN ISO 11137-1, Sterilization of health care products Radiation Part 1: Requirements for developme
13、nt, validation and routine control of a sterilization process for medical devices DIN EN ISO 11137-3, Sterilization of health care products Radiation Part 3: Guidance on dosimetric aspects DIN EN ISO 11737-1, Sterilization of medical devices Microbiological methods Part 1: Determination of a populat
14、ion of microorganisms on products DIN EN ISO 11737-2, Sterilization of medical devices Microbiological methods Part 2: Tests of sterility performed in the definition, validation and maintenance of a sterilization process DIN EN ISO 13485, Medical devices Quality management systems Requirements for r
15、egulatory purposes DIN EN ISO 14971, Medical devices Application of risk management to medical devices EUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NORM EN ISO 11137-2 June 2015 ICS 11.080.01 Supersedes EN ISO 11137-2:2013 English Version Sterilization of health care products - Radiation - Part 2: E
16、stablishing the sterilization dose (ISO 11137-2:2013) Strilisation des produits de sant - Irradiation - Partie 2: tablissement de la dose strilisante (ISO 11137-2:2013) Sterilisation von Produkten fr die Gesundheitsfrsorge - Strahlen - Teil 2: Festlegung der Sterilisationsdosis (ISO 11137-2:2013) Th
17、is European Standard was approved by CEN on 20 May 2015. 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 reference
18、s 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 mem
19、ber 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, Fr
20、ance, Germany, Greece, Hungary, 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 C O M I T EUR O P EN D E NOR M A L I S A T
21、I O N EUR O P I S C H E S KOM I T E E F R NOR M UNG CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels 2015 CEN All rights of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO 11137-2:2015 E Contents PageForeword 4Introduction 51 Sco
22、pe . 62 Normative references 63 Terms, definitions, and abbreviated terms . 63.1 Terms and definitions . 63.2 Abbreviated terms . 84 Definition and maintenance of product families for dose setting, dose substantiation, and sterilization dose auditing . 94.1 General . 94.2 Defining product families 9
23、4.3 Designation of product to represent a product family for performance of a verification dose experiment or sterilization dose audit . 104.4 Maintaining product families 114.5 Effect of failure of establishment of sterilization dose or of a sterilization dose audit on a product family. 125 Selecti
24、on and testing of product for establishing the sterilization dose 125.1 Nature of product 125.2 Sample item portion (SIP) 135.3 Manner of sampling . 145.4 Microbiological testing 145.5 Irradiation 146 Methods of dose establishment . 147 Method 1: dose setting using bioburden information 157.1 Ration
25、ale 157.2 Procedure for Method 1 for product with an average bioburden greater than or equal to 1,0 for multiple production batches 167.3 Procedure for Method 1 for product with an average bioburden greater than or equal to 1,0 for a single production batch . 227.4 Procedure for Method 1 for product
26、 with an average bioburden in the range 0,1 to 0,9 for multiple or single production batches . 248 Method 2: Dose setting using fraction positive information from incremental dosing to determine an extrapolation factor .258.1 Rationale 258.2 Procedure for Method 2A 268.3 Procedure for Method 2B 299
27、Method VDmax Substantiation of 25 kGy or 15 kGy as the sterilization dose .339.1 Rationale 339.2 Procedure for Method VDmax25for multiple production batches .349.3 Procedure for Method VDmax25for a single production batch .399.4 Procedure for Method VDmax15for multiple production batches .429.5 Proc
28、edure for Method VDmax15for a single production batch .4510 Sterilization dose audit .4810.1 Purpose and frequency . 4810.2 Procedure for auditing a sterilization dose established using Method 1, Method 2A, or Method 2B 4810.3 Procedure for auditing a sterilization dose substantiated using Method VD
29、max25or Method VDmax1510.4 Failure of a sterilization dose audit 5711 Worked examples .57DIN EN ISO 11137-2:2015-11 EN ISO 11137-2:2015 (E) 25111.1 Worked examples for Method 1 5711.2 Worked examples for Method 2 5911.3 Worked examples for Method VDmax11.4 Worked example of a sterilization dose audi
30、t for a dose established using Method 1, the findings from which necessitated augmentation of the sterilization dose 6911.5 Worked example of a sterilization dose audit for a dose established using Method 2A, the findings from which necessitated augmentation of the sterilization dose 6911.6 Worked e
31、xample of a sterilization dose audit for a sterilization dose substantiated using Method VDmax25.Bibliography .76Annex ZA (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 90/385/EEC on active implantable medical devices Annex ZB (informative) R
32、elationship between this European Standard and the Essential Requirements of EU Directive 93/42/EEC on medical devices Annex ZC (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devicesDIN EN ISO 11137-2:2
33、015-11 EN ISO 11137-2:2015 (E) 36770. 72.7374Foreword The text of ISO 11137-2:2013 has been prepared by Technical Committee ISO/TC 198 “Sterilization of health care products” of the International Organization for Standardization (ISO) and has been taken over as EN ISO 11137-2:2015 by Technical Commi
34、ttee 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 December 2015, and conflicting national standards shall
35、be withdrawn at the latest by December 2015. Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. CEN and/or CENELEC shall not be held responsible for identifying any or all such patent rights. This document supersedes EN ISO 11137-2:2
36、013. 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 Directives. For relationship with EU Directives, see informative Annexes ZA, ZB and ZC, which are integral parts of this doc
37、ument. The following referenced documents are indispensable for the application of this document. For undated references, the edition of the referenced document (including any amendments) listed below applies. For dated references, only the edition cited applies. However, for any use of this standar
38、d within the meaning of Annex ZA, ZB or ZC, the user should always check that any referenced document has not been superseded and that its relevant contents can still be considered the generally acknowledged state-of-art. When an IEC or ISO standard is referred to in the ISO standard text, this shou
39、ld be understood as a normative reference to the corresponding EN standard, if available, and otherwise to the dated version of the ISO or IEC standard as listed below. NOTE The way in which these referenced documents are cited in normative requirements determines the extent (in whole or in part) to
40、 which they apply. Table Correlation between normative references and dated EN and ISO standards Normative references as listed in Clause 2 of the ISO standard Equivalent dated standard EN ISO ISO 11137 EN ISO 11137-1:2006/A1:2013 ISO 11137-1:2006/A1:2013 ISO 11737-1 EN ISO 11737-1:2006 + AC:2009 IS
41、O 11737-1:2006 + Cor 1:2007 ISO 11737-2 EN ISO 11737-2:2009 ISO 11737-2:2009 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,
42、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, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom. Endorsemen
43、t notice The text of ISO 11137-2:2013 has been approved by CEN as EN ISO 11137-2:2015 without any modification. DIN EN ISO 11137-2:2015-11 EN ISO 11137-2:2015 (E) 4 IntroductionThis part of ISO 11137 describes methods that can be used to establish the sterilization dose in accordance with one of the
44、 two approaches specified in 8.2 of ISO 11137-1:2006. The methods used in these approaches are: dose setting to obtain a product-specific dose; dose substantiation to verify a preselected dose of 25 kGy or 15 kGy.The basis of the dose setting methods described in this part of ISO 11137 (Methods 1 an
45、d 2) owe much to the ideas first propounded by Tallentire192021. Subsequently, standardized protocols were developed1011, which formed the basis of the dose setting methods detailed in the AAMI Recommended Practice for Sterilization by Gamma Radiation68.Methods 1 and 2 and the associated sterilizati
46、on dose audit procedures use data derived from the inactivation of the microbial population in its natural state on product. The methods are based on a probability model for the inactivation of microbial populations. The probability model, as applied to bioburden made up of a mixture of various micr
47、obial species, assumes that each such species has its own unique D10value. In the model, the probability that an item will possess a surviving microorganism after exposure to a given dose of radiation is defined in terms of the initial number of microorganisms on the item prior to irradiation and th
48、e D10values of the microorganisms. The methods involve performance of tests of sterility on product items that have received doses of radiation lower than the sterilization dose. The outcome of these tests is used to predict the dose needed to achieve a predetermined sterility assurance level (SAL).
49、Methods 1 and 2 can also be used to substantiate 25 kGy if, on performing a dose setting exercise, the derived sterilization dose for an SAL of 106is less than or equal to 25 kGy. The basis of the method devised specifically for substantiation of 25 kGy, Method VDmax, was put forward by Kowalski and Tallentire16. Subsequent evaluations involving com
