1、BSI Standards Publication Sterilization of health care products Radiation Substantiation of selected sterilization dose: Method VD max SD PD CEN ISO/TS 13004:2014PD CEN ISO/TS 13004:2014 National foreword This Published Document is the UK implementation of CEN ISO/TS 13004:2014. It is identical to I
2、SO/TS 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 It supersedes PD ISO/TS 13004:2013, which is withdrawn.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 pub
3、lication 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 2014 ISBN 978 0 580 85152 0 ICS 11.080.01 Compliance with a British Standard cannot confer im
4、munity from legal obligations. This Published Document was published under the authority of the Standards Policy and Strategy Committee on 28 February 2014. Amendments/corrigenda issued since publication Date Text affected 31 July 2014 This corrigendum renumbers PD ISO/TS 13004:2013 as PD CEN ISO/TS
5、 13004:2014 PUBLISHED DOCUMENT TECHNICAL 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) Strilis
6、ation des produits 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 Specifica
7、tion (CEN/TS) was approved 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 int
8、o a European Standard. 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) unti
9、l the final decision 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, Ic
10、eland, 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-CENELEC Man
11、agement 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. CEN ISO/TS 13004:2014 E ii ISO 2013 All rights reserved Foreword The text of ISO/TS 13004:2013 has been prepared by Technical Commi
12、ttee ISO/TC 198 “Sterilization 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
13、 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. According to the CEN-CENELEC Internal Regulations, the national standards organizations of the following countr
14、ies are bound to announce 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,
15、 Poland, Portugal, Romania, 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 right
16、s reserved iii Contents Page Foreword iv Introduction v 1 Scope . 1 1.1 Inclusions . 1 1.2 Exclusions 1 1.3 Application . 1 2 Normative references 1 3 T erms and definitions . 1 4 Definition and maint enanc e of pr oduct families for st erilization dose substantiation and sterilization dose auditing
17、 . 5 4.1 General . 5 4.2 Defining product families 5 4.3 Designation of product to represent a product family 6 4.4 Maintaining product families . 7 4.5 Consequence of failure of sterilization dose substantiation or sterilization dose audit . 8 5 Selection and testing of product for substantiating a
18、nd auditing a selected sterilization dose 8 5.1 Nature of product . 8 5.2 Sample item portion (SIP) . 9 5.3 Manner of sampling .10 5.4 Microbiological testing 11 5.5 Irradiation 11 6 Method Substantiation of a selected sterilization dose of 17,5, 20, 22,5, 27,5, 30, 32,5, or 35 kGy .11 6.1 Rationale
19、11 6.2 Procedure for Method for multiple production batches 12 6.3 Procedure for Method for a single production batch 17 7 Maintaining process effectiveness 21 7.1 General 21 7.2 Determination of bioburden 22 7.3 Sterilization dose audit .22 8 Tables of values for SIP equal to 1,0 VD max SD , SIP do
20、se reduction factor and augmentation 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 .27 9 Worked examples .53 9.1 Substantiation of a selected sterilization dose of 17,5 kGy (SIP less than 1,0) 53 9.2 Substan
21、tiation of a selected sterilization dose of 30 kGy (SIP equal to 1,0) .54 9.3 Sterilization dose audit for a sterilization dose substantiated using Method VD max 22,5 , the findings from which necessitated augmentation of the sterilization dose 55 Bibliography .57 PD CEN ISO/TS 13004:2014 ISO/TS 130
22、04:2013 (E) Foreword ISO (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 f
23、or 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 International Electrotechnical Commission (IEC) on
24、 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 prepare International Standards. Draft International Standards adopted by the technical committees a
25、re 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. In other circumstances, particularly when there is an urgent market requirement for such documents, a technical committee may decide to publ
26、ish other types of normative document: an ISO Publicly 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 Technic
27、al Specification (ISO/TS) represents an agreement 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 f
28、or a further three years, revised to become an International 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 possibil
29、ity 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 rights. ISO/TS 13004 was prepared by Technical Committee ISO/TC 198, Sterilization of health care products.iv ISO 2013 All rights reserved PD C
30、EN ISO/TS 13004:2014 ISO/TS 13004:2013 (E) Introduction This 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 dev
31、ices. One of the activities encompassed within process 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 for the substantiation of 25 kGy as a sterilization dose (termed Method VD max 25 ) for pr
32、oduct with an average bioburden less than or equal to 1 000 and Method VD max 15for 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 sterilizatio
33、n dose specified in ISO 11137-2. It provides a methodology 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
34、 included in this Technical Specification. The seven methods 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
35、 has been modified to better communicate the methods and 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 10 6or less at that dose,
36、 (e.g. Method VD max 20for a selected sterilization dose of 20 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 t
37、he following three principles: existence of a direct link between the outcome of the verification dose experiment and the attainment of an SAL of 10 6at the selected sterilization dose; possession of a level of conservativeness at least equal to that of the standard distribution of resistances (SDR)
38、; for a given bioburden, use of a maximal verification dose (VD max ) corresponding to substantiation of a selected sterilization dose. This approach to sterilization dose substantiation was first outlined by Kowalski and Tallentire 6and, from subsequent evaluations involving computational technique
39、s (Kowalski, Aoshuang and Tallentire 7 ) and field evaluations (Kowalski et al 8 ), 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 approach to doses other than
40、25 kGy is discussed in Kowalski and Tallentire. 1112 The method described here and designated Method procedurally 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
41、experiment. In the computer evaluations referred to above, changing 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. Manu
42、facturers of health care products who intend to use this specification 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 manufacture
43、d in circumstances such that the bioburden is controlled. Compliance 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 A
44、ll rights reserved v PD CEN ISO/TS 13004:2014 ISO/TS 13004:2013 (E)PD CEN ISO/TS 13004:2014 ISO/TS 13004:2013 (E) Sterilization of health care products Radiation Substantiation of selected sterilization dose: Method VD max SD 1 Scope 1.1 Inclusions This Technical Specification describes a method for
45、 substantiating a selected sterilization dose of 17,5, 20, 22,5, 27,5, 30, 32,5 or 35 kGy that achieves a sterility assurance level (SAL) of 10 6or less for radiation sterilization of health care products. This Technical Specification also specifies a method of sterilization dose audit used to demon
46、strate the continued effectiveness of the substantiated sterilization 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 Exclusions This method is for the substantiat
47、ion of a selected sterilization dose of 17,5, 20, 22,5, 27,5, 30, 32,5, or 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 speci
48、fied for the selected sterilization dose (see Table 3). NOTE The methods for 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 Application If the decision is made to use this method of steriliz
49、ation dose establishment, the method is to be followed according to the requirements (shall) and guidance (should) stipulated herein. 2 Normative references The 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
