1、September 2011 Translation by DIN-Sprachendienst.English price group 13No 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).
2、ICS 11.080.01!$tk#“1817200www.din.deDDIN EN ISO 13408-5Aseptic processing of health care products Part 5: Sterilization in place (ISO 13408-5:2006)English translation of DIN EN ISO 13408-5:2011-09Aseptische Herstellung von Produkten fr die Gesundheitsfrsorge Teil 5: Sterilisation vor Ort (ISO 13408-
3、5:2006)Englische bersetzung von DIN EN ISO 13408-5:2011-09Traitement aseptique des produits de sant Partie 5: Strilisation sur place (ISO 13408-5:2006)Traduction anglaise de DIN EN ISO 13408-5:2011-09Together with DIN EN ISO 13408-1:2011-09, DIN EN ISO 13408-2:2011-09, DIN EN ISO 13408-3:2011-09,DIN
4、 EN ISO 13408-4:2011-09 and DIN EN ISO 13408-6:2011-09 supersedes DIN EN 13824:2005-02Supersedes: see belowwww.beuth.deDocument comprises pagesIn case of doubt, the German-language original shall be considered authoritative.2509.11 DIN EN ISO 13408-5:2011-09 National foreword This standard has been
5、prepared by Technical Committee ISO/TC 198 “Sterilization of health care products” (Secretariat: ANSI, United States) in collaboration with Technical Committee CEN/TC 204 “Sterilization of medical devices” (Secretariat: BSI, United Kingdom). The responsible German body involved in its preparation wa
6、s the Normenausschuss Medizin (Medical Standards Committee), Working Committee NA 063-01-12 AA Aseptische Herstellung. ISO 13408 consists of the following parts, under the general title Aseptic processing of health care products: Part 1: General requirements Part 2: Filtration Part 3: Lyophilization
7、 Part 4: Clean-in-place technologies Part 5: Sterilization in place Part 6: Isolator systems The following parts are in preparation: Part 7: Alternative processes for atypical medical devices and combination products Part 8: Cell based health care products Parts 1 to 6 of the DIN EN ISO 13408 series
8、 supersede DIN EN 13824, Sterilization of medical devices Aseptic processing of liquid medical devices Requirements. The DIN Standards corresponding to the International Standards referred to in this standard are as follows: ISO 9000 DIN EN ISO 9000 ISO 11138 (all parts) DIN EN ISO 11138 (all parts)
9、 ISO 11140 (all parts) DIN EN ISO 11140 (all parts) ISO 13408-1 DIN EN ISO 13408-1 ISO 13408-4 DIN EN ISO 13408-4 ISO 14161 DIN EN ISO 14161 ISO 14937 DIN EN ISO 14937 ISO 17665-1 DIN EN ISO 17665-1 ISO 22442 (all parts) DIN EN ISO 22442 (all parts) Amendments This standard differs from DIN EN 13824
10、:2005-02 as follows: a) the specifications relating to the sterilization in place have been updated and rendered more precise. Previous editions DIN EN 13824: 2005-02 2 DIN EN ISO 13408-5:2011-09 National Annex NA (informative) Bibliography DIN EN ISO 9000, Quality management systems Fundamentals an
11、d vocabulary DIN EN ISO 11138 (all parts), Sterilization of health care products Biological indicators DIN EN ISO 11140 (all parts), Sterilization of health care products Chemical indicators DIN EN ISO 13408-1, Aseptic processing of health care products Part 1: General requirements DIN EN ISO 13408-
12、4, Aseptic processing of health care products Part 4: Clean-in-place technologies DIN EN ISO 14161, Sterilization of health care products Biological indicators Guidance for the selection, use and interpretation of results DIN EN ISO 14937, Sterilization of health care products General requirements f
13、or characterization of a sterilizing agent and the development, validation and routine control of a sterilization process for medical devices DIN EN ISO 17665-1, Sterilization of health care products Moist heat Part 1: Requirements for the development, validation and routine control of a sterilizati
14、on process for medical devices DIN EN ISO 22442 (all parts), Medical devices utilizing animal tissues and their derivatives 3 DIN EN ISO 13408-5:2011-09 4 This page is intentionally blank EUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NORM EN ISO 13408-5 June 2011 ICS 11.080.01 Supersedes EN 13824:200
15、4English Version Aseptic processing of health care products - Part 5: Sterilization in place (ISO 13408-5:2006) Traitement aseptique des produits de sant - Partie 5: Strilisation sur place (ISO 13408-5:2006) Aseptische Herstellung von Produkten fr die Gesundheitsfrsorge - Teil 5: Sterilisation vor O
16、rt (ISO 13408-5:2006) This European Standard was approved by CEN on 10 June 2011. 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
17、bibliographical references 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 re
18、sponsibility of a CEN member 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, France, Germany,
19、 Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom. EUROPEAN COMMITTEE FOR STANDARDIZATION COMIT EUROPEN DE NORMALISATION EUROPISCHES KOMITEE FR NORMUNG Man
20、agement Centre: Avenue Marnix 17, B-1000 Brussels 2011 CEN All rights of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO 13408-5:2011: EContents Page1 Scope .52 Normative references .53 Terms and definitions .64 Quality system elements 74.1 Gene
21、ral 74.2 Management responsibility .74.3 Design control 74.4 Measuring instruments and measuring systems 75 Process and equipment characterization . 85.1 General concepts .85.2 Effectiveness of sterilization in place (SIP) .85.3 Equipment .86 Sterilizing agent characterization .106.1 Selection of st
22、erilizing agent(s) 6.2 Quality of sterilizing agent(s) . .106.3 Safety and the environment 107 SIP process .107.1 Process parameters .7.2 Cycle development .118 Validation .118.1 Validation protocol .118.2 Design qualification .118.3 Installation qualification 118.4 Operational qualification .128.5
23、Performance qualification .128.6 Review and approval of validation 148.7 Requalification 149 Routine monitoring and control 149.1 SIP process control 149.2 Procedures 149.3 SIP process records .159.4 Change control . 159.5 Maintenance of equipment 1510 Personnel training 15Annex A (informative) Stea
24、m sterilization in place 16Bibliography 20Annex ZA (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices 17Annex ZB (informative) Relationship between this European Standard and the Essential Requirem
25、ents of EU Directive 93/42/EEC on Medical Devices .18Annex ZC (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devices 19EN ISO 13408-5:2011 (E) DIN EN ISO 13408-5:2011-09 2Foreword. 3 Introduction 4 1010
26、Foreword The text of ISO 13408-5:2006 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 13408-5:2011 by Technical Committee CEN/TC 204 “Sterilization of medical dev
27、ices” 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 2011, and conflicting national standards shall be withdrawn at the latest by December 2011.
28、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 13824:2004. This document has been prepared under a mandat
29、e 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, or ZC, which are integral parts of this document. According to the CEN/CENELEC Internal Regula
30、tions, the national standards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malt
31、a, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 13408-5:2006 has been approved by CEN as a EN ISO 13408-5:2011 without any modification. EN ISO 13408-5:2011 (E) DIN EN ISO 13408-5:2011-09 3In
32、troductionDuring the process of preparing ISO 13408-1, several items, e.g. filtration, freeze drying and sterilization inplace, were found to be in need of supplementary information which was too voluminous to be given incorresponding annexes.This part of ISO 13408 includes requirements and guidance
33、 that are to be observed during sterilization in place.The purpose of this part of ISO 13408 is to achieve standardization in the field of validation and routine controlof sterilization in place processes used in the manufacture of health care products.Sterilization in place is, in most instances, p
34、receded by cleaning in place which is described in ISO 13408-4.While methods of cleaning in place and sterilization in place differ considerably in technology, the concept of insitu treatment is similar.The most important issue to consider in establishing sterilization-in-place technology is the des
35、ign of thesystem(s) to ensure that they be able to successfully sterilize manufacturing equipment to the desired level ofsterility assurance.EN ISO 13408-5:2011 (E) DIN EN ISO 13408-5:2011-09 41Scope1.1 This part of ISO 13408 specifies the general requirements for sterilization in place (SIP) applie
36、d to productcontact surfaces of the equipment used in the manufacture of sterile health care products by aseptic processingand offers guidance on qualification, validation, operation and control.NOTE SIP can be achieved by using steam or other gaseous or liquid sterilizing agents. Specific guidance
37、on steamsterilization in place, which is the most common method used, is given in Annex A.1.2 This part of ISO 13408 applies to processes where sterilizing agents are delivered to the internal surfacesof equipment that can come in contact with the product.1.3 This part of ISO 13408 does not apply to
38、 processes where equipment is dismantled and delivered to asterilizer.1.4 This part of ISO 13408 does not supersede or replace national regulatory requirements, such as GoodManufacturing Practices (GMPs) and/or compendial requirements that pertain in particular national or regionaljurisdictions.1.5
39、This part of ISO 13408 does not specify requirements for development, validation and routine control of aprocess for inactivating the causative agents of spongiform encephalopathies, such as scrapie, bovinespongiform encephalopathy and Creutzfeldt-Jakob disease. Specific recommendations have been pr
40、oduced inparticular countries for the processing of materials potentially contaminated with these agents. NOTE See also ISO 22442-1, ISO 22442-2 and ISO 22442-3.2 Normative referencesThe following referenced documents are indispensable for the application of this document. For datedreferences, only
41、the edition cited applies. For undated references, the latest edition of the referenced document(including any amendments) applies.ISO 11138 (all parts), Sterilization of health care products Biological indicatorsISO 11140 (all parts), Sterilization of health care products Chemical indicatorsISO 134
42、08-1, Aseptic processing of health care products Part 1: General requirementsISO 13408-4, Aseptic processing of health care products Part 4: Clean-in-place technologiesISO 14161, Sterilization of health care products Biological indicators Guidance for the selection, use andinterpretation of resultsI
43、SO 14937, Sterilization of health care products General requirements for characterization of a sterilizingagent and the development, validation and routine control of a sterilization process for medical devicesEN ISO 13408-5:2011 (E) DIN EN ISO 13408-5:2011-09 5ISO 17665-1, Sterilization of health c
44、are products Moist heat Part 1: Requirements for the development,validation and routine control of a sterilization process for medical devicesISO/IEC 90003, Software engineering Guidelines for the application of ISO 9001:2000 to computer software3 Terms and definitionsFor the purposes of this docume
45、nt, the terms and definitions given in ISO 13408-1 and the following apply.3.1 dead leglocation which, by design, does not permit adequate accessibility of the sterilizing agent3.2 design qualificationverification that the proposed specification for the facility, equipment or system is suitable for
46、the intended useISO/TS 11139:2006, definition 2.123.3 material safety data sheetMSDSdocument specifying the properties of a substance, its potential hazardous effects for humans and theenvironment, and the precautions necessary to handle and dispose of the substance safelyISO/TS 11139:2006, definiti
47、on 2.233.4 process parameterspecified value for a process variableNOTE The specification for a sterilization process includes the process parameters and their tolerances.ISO/TS 11139:2006, definition 2.343.5 process variablecondition within a sterilization process, changes in which alter microbicida
48、l effectivenessEXAMPLE Time, temperature, pressure, concentration, humidity, wavelength.ISO/TS 11139:2006, definition 2.353.6 sterilization in placeSIPmethod of sterilization of the internal surfaces of parts of the equipment or an entire process system in situ,without disassembly, using appropriate
49、 sterilizing agentsNOTE The term “Steam in place” is used in ISO 13408-1, Clause 19, and this term is sometimes abbreviated as SIP.However, in this part of ISO 13408, “SIP” is used with a wider meaning and includes not only steam in place, but all kinds ofsterilization used for the sterilization “in place” or “in situ”. In this part of ISO 13408, “Steam sterilization in place” is referredto as “Steam SIP”.EN ISO 13408-5:2011 (E) DIN EN ISO 13408-5:2011-09 63.7 sterility assurance levelSALprob
