1、BSI Standards PublicationSterilization of health care products Radiation Substantiation of selected sterilization dose: Method VDmaxSDPD CEN ISO/TS 13004:2014PD CEN ISO/TS 13004:2014National forewordThis Published Document is the UK implementation of CEN ISO/TS 13004:2014. It is identical to ISO/TS
2、13004:2013. It supersedes PD ISO/TS 13004:2013, which is withdrawn.The UK participation in its preparation was entrusted to Technical Committee CH/198, Sterilization of medical devices.A list of organizations represented on this committee can be obtained on request to its secretary.This publication
3、does not purport to include all the necessary provisions of a contract. Users are responsible for its correct application. The British Standards Institution 2014. Published by BSI Standards Limited 2014ISBN 978 0 580 85152 0ICS 11.080.01Compliance with a British Standard cannot confer immunity froml
4、egal obligations.This Published Document was published under the authority of the Standards Policy and Strategy Committee on 28 February 2014.Amendments/corrigenda issued since publicationDate Text affected31 July 2014 This corrigendum renumbers PD ISO/TS 13004:2013 as PD CEN ISO/TS 13004:2014PUBLIS
5、HED DOCUMENTTECHNICAL SPECIFICATION SPCIFICATION TECHNIQUE TECHNISCHE SPEZIFIKATION CEN ISO/TS 13004 May 2014 ICS 11.080.01 English Version Sterilization of health care products - Radiation - Substantiation of selected sterilization dose: Method VDmaxSD (ISO/TS 13004:2013) Strilisation des produits
6、de sant - Irradiation - Justification de la dose de strilisation choisie: mthode VDmaxSD (ISO/TS 13004:2013) Sterilisation von Produkten fr die Gesundheitsfrsorge - Strahlen - Besttigung der gewhlten Sterilisationsdosis: Methode VDmaxSD (ISO/TS 13004:2013) This Technical Specification (CEN/TS) was a
7、pproved by CEN on 27 May 2014 for provisional application. The period of validity of this CEN/TS is limited initially to three years. After two years the members of CEN will be requested to submit their comments, particularly on the question whether the CEN/TS can be converted into a European Standa
8、rd. CEN members are required to announce the existence of this CEN/TS in the same way as for an EN and to make the CEN/TS available promptly at national level in an appropriate form. It is permissible to keep conflicting national standards in force (in parallel to the CEN/TS) until the final decisio
9、n about the possible conversion of the CEN/TS into an EN is reached. 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, Ita
10、ly, 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-CENELEC Management Centre: Ave
11、nue 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. CEN ISO/TS 13004:2014 Eii ISO 2013 All rights reservedForeword The text of ISO/TS 13004:2013 has been prepared by Technical Committee ISO/TC 198 “Ster
12、ilization of health care products” of the International Organization for Standardization (ISO) and has been taken over as CEN ISO/TS 13004:2014 by Technical Committee CEN/TC 204 “Sterilization of medical devices” the secretariat of which is held by BSI. Attention is drawn to the possibility that som
13、e 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. According to the CEN-CENELEC Internal Regulations, the national standards organizations of the following countries are bound to anno
14、unce this Technical Specification: 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, Ro
15、mania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom. Endorsement notice The text of ISO/TS 13004:2013 has been approved by CEN as CEN ISO/TS 13004:2014 without any modification. PD CEN ISO/TS 13004:2014 CEN ISO/TS 13004:2014(E) ISO 2013 All rights reserved iiiContent
16、s PageForeword ivIntroduction v1 Scope . 11.1 Inclusions . 11.2 Exclusions 11.3 Application . 12 Normative references 13 Terms and definitions . 14 Definition and maintenance of product families for sterilization dose substantiation and sterilization dose auditing . 54.1 General . 54.2 Defining prod
17、uct families 54.3 Designation of product to represent a product family 64.4 Maintaining product families . 74.5 Consequence of failure of sterilization dose substantiation or sterilization dose audit . 85 Selection and testing of product for substantiating and auditing a selected sterilization dose
18、85.1 Nature of product . 85.2 Sample item portion (SIP) . 95.3 Manner of sampling . 105.4 Microbiological testing 115.5 Irradiation 116 Method VDSDmax Substantiation of a selected sterilization dose of 17,5, 20, 22,5, 27,5, 30, 32,5, or 35 kGy .116.1 Rationale 116.2 Procedure for Method VDSDmaxfor m
19、ultiple production batches 126.3 Procedure for Method VDSDmaxfor a single production batch 177 Maintaining process effectiveness 217.1 General 217.2 Determination of bioburden 227.3 Sterilization dose audit . 228 Tables of values for SIP equal to 1,0 VDmaxSD, SIP dose reduction factor and augmentati
20、on dose corresponding to applicable values of average bioburden for selected sterilization doses of 17,5, 20, 22,5, 27,5, 30, 32,5 and 35 kGy .279 Worked examples .539.1 Substantiation of a selected sterilization dose of 17,5 kGy (SIP less than 1,0) 539.2 Substantiation of a selected sterilization d
21、ose of 30 kGy (SIP equal to 1,0) .549.3 Sterilization dose audit for a sterilization dose substantiated using Method VDmax22,5, the findings from which necessitated augmentation of the sterilization dose 55Bibliography .57PD CEN ISO/TS 13004:2014 ISO/TS 13004:2013 (E)ForewordISO (the International O
22、rganization 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 estab
23、lished 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 standardizat
24、ion.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 prepare International Standards. Draft International Standards adopted by the technical committees are circulated to the member bodies for voting.
25、Publication as an International Standard requires approval by at least 75 % of the member bodies casting a vote.In other circumstances, particularly when there is an urgent market requirement for such documents, a technical committee may decide to publish other types of normative document: an ISO Pu
26、blicly Available Specification (ISO/PAS) represents an agreement between technical experts in an ISO working group and is accepted for publication if it is approved by more than 50 % of the members of the parent committee casting a vote; an ISO Technical Specification (ISO/TS) represents an agreemen
27、t between the members of a technical committee and is accepted for publication if it is approved by 2/3 of the members of the committee casting a vote.An ISO/PAS or ISO/TS is reviewed after three years in order to decide whether it will be confirmed for a further three years, revised to become an In
28、ternational Standard, or withdrawn. If the ISO/PAS or ISO/TS is confirmed, it is reviewed again after a further three years, at which time it must either be transformed into an International Standard or be withdrawn.Attention is drawn to the possibility that some of the elements of this document may
29、 be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights.ISO/TS 13004 was prepared by Technical Committee ISO/TC 198, Sterilization of health care products.iv ISO 2013 All rights reservedPD CEN ISO/TS 13004:2014 ISO/TS 13004:2013 (E)Introducti
30、onThis Technical Specification is intended to be used in conjunction with 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. One of the activities encompassed within process
31、 definition in ISO 11137-1 is the option to select and substantiate a sterilization dose to be applied to health care products.ISO 11137-2 includes Method VDmaxfor the substantiation of 25 kGy as a sterilization dose (termed Method VDmax25) for product with an average bioburden less than or equal to
32、 1 000 and Method VDmax15for the substantiation of 15 kGy as a sterilization dose for product with an average bioburden less than or equal to 1,5.This Technical Specification extends the methods of selection and substantiation of a sterilization dose specified in ISO 11137-2. It provides a methodolo
33、gy for the substantiation of selected sterilization doses of 17,5, 20, 22,5, 27,5, 30, 32,5 and 35 kGy, each of which is valid only for a specified upper limit of average bioburden.NOTE Selected sterilization doses of 25 kGy and 15 kGy are not included in this Technical Specification. The seven meth
34、ods in this Technical Specification follow the same technical steps as the methods given in ISO 11137-2 for selection and substantiation of sterilization doses of 25 kGy and 15 kGy. However, the descriptive text in this Technical Specification has been modified to better communicate the methods and
35、hence the text occasionally differs from that in ISO 11137-2.The method described in this Technical Specification is for substantiation of a selected sterilization dose to achieve a sterility assurance level (SAL) of 106or less at that dose, (e.g. Method VDmax20for a selected sterilization dose of 2
36、0 kGy). The application of the method is not limited by production batch size or production frequency, and the number of product items irradiated in the verification dose experiment remains constant. The method is founded on and embodies the following three principles: existence of a direct link bet
37、ween the outcome of the verification dose experiment and the attainment of an SAL of 106at the selected sterilization dose; possession of a level of conservativeness at least equal to that of the standard distribution of resistances (SDR); for a given bioburden, use of a maximal verification dose (V
38、Dmax) corresponding to substantiation of a selected sterilization dose.This approach to sterilization dose substantiation was first outlined by Kowalski and Tallentire6and, from subsequent evaluations involving computational techniques (Kowalski, Aoshuang and Tallentire7) and field evaluations (Kowa
39、lski et al8), it was concluded that the method is soundly based. An overview of the method and aspects of putting it into practice are provided in Kowalski and Tallentire.910Application of the Method VDmaxapproach to doses other than 25 kGy is discussed in Kowalski and Tallentire.1112The method desc
40、ribed here and designated Method VDSDmaxprocedurally comprises elements that closely parallel those of dose setting Method 1 described in ISO 11137-2. One key area of difference is the number of product items used in the verification dose experiment. In the computer evaluations referred to above, ch
41、anging the verification SAL value had little effect on the substantiation outcome and this finding led to a sample size of 10 product items being chosen for subsequent field evaluations and, ultimately, for inclusion in this document.Manufacturers of health care products who intend to use this speci
42、fication are reminded that the requirements contained in ISO 11137 apply to the manufacture and control of production batches destined for radiation sterilization. In particular, one requirement states that products have to be manufactured in circumstances such that the bioburden is controlled. Comp
43、liance with the requirements for controlling the quality of raw materials, the manufacturing environment, the health, hygiene and attire of personnel and for establishing the basic properties of packaging material is essential. ISO 2013 All rights reserved vPD CEN ISO/TS 13004:2014 ISO/TS 13004:2013
44、 (E)PD CEN ISO/TS 13004:2014 ISO/TS 13004:2013 (E)Sterilization of health care products Radiation Substantiation of selected sterilization dose: Method VDmaxSD1 Scope1.1 InclusionsThis Technical Specification describes a method for substantiating a selected sterilization dose of 17,5, 20, 22,5, 27,5
45、, 30, 32,5 or 35 kGy that achieves a sterility assurance level (SAL) of 106or less for radiation sterilization of health care products. This Technical Specification also specifies a method of sterilization dose audit used to demonstrate the continued effectiveness of the substantiated sterilization
46、dose.NOTE Selection and substantiation of the sterilization dose is used to meet the requirements for establishing the sterilization dose within process definition in ISO 11137-1.1.2 ExclusionsThis method is for the substantiation of a selected sterilization dose of 17,5, 20, 22,5, 27,5, 30, 32,5, o
47、r 35 kGy only and is not used to substantiate other sterilization doses. The method is not used for the substantiation of a selected sterilization dose if the average bioburden of the entire product item exceeds the limit specified for the selected sterilization dose (see Table 3).NOTE The methods f
48、or substantiation of selected sterilization doses of 25 kGy and 15 kGy are not included in this Technical Specification; they are described in ISO 11137-2.1.3 ApplicationIf the decision is made to use this method of sterilization dose establishment, the method is to be followed according to the requ
49、irements (shall) and guidance (should) stipulated herein.2 Normative referencesThe following referenced documents are indispensable for the application 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 11137-1:2006, Sterilization of health care products Radiation Part 1: Requirements for development, validation and routine control of a sterilization process for medical devicesISO 11737-1, Steri
