DIN EN ISO 13408-1-2015 Aseptic processing of health care products - Part 1 General requirements (ISO 13408-1 2008 including Amd 1 2013) German version EN ISO 13408-1 2015《保健品无菌加工 .pdf

1、December 2015 English price group 24No 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 11.080.01!%IL“2384191www.din.de

2、DIN EN ISO 13408-1Aseptic processing of health care products Part 1: General requirements (ISO 13408-1:2008, including Amd 1:2013);English version EN ISO 13408-1:2015,English translation of DIN EN ISO 13408-1:2015-12Aseptische Herstellung von Produkten fr die Gesundheitsfrsorge Teil 1: Allgemeine An

3、forderungen (ISO 13408-1:2008, einschlielich Amd 1:2013);Englische Fassung EN ISO 13408-1:2015,Englische bersetzung von DIN EN ISO 13408-1:2015-12Traitement aseptique des produits de sant Partie 1: Exigences gnrales (ISO 13408-1:2008, y compris Amd 1:2013);Version anglaise EN ISO 13408-1:2015,Traduc

4、tion anglaise de DIN EN ISO 13408-1:2015-12SupersedesDIN EN ISO 13408-1:2013-08www.beuth.deDocument comprises 62 pagesDTranslation by DIN-Sprachendienst.In case of doubt, the German-language original shall be considered authoritative.11.15 DIN EN ISO 13408-1:2015-12 2 A comma is used as the decimal

5、marker. National foreword This document (EN ISO 13408-1:2015) 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

6、 body involved in its preparation was DIN-Normenausschuss Medizin (DIN Standards Committee Medical), Working Committee NA 063-01-12 AA Aseptische Herstellung. According to Resolution CEN/BT C50/2015 Annexes ZA, ZB and ZC and the European Foreword have been updated and published in June 2015 as a new

7、 edition of EN ISO 13408-1:2015. Thus, this new edition of DIN EN ISO 13408-1 has also been published. It includes the texts of ISO 13408-1:2008 and ISO 13408-1:2008 Amendment 1:2013 without any modification. DIN EN ISO 13408 consists of the following parts, under the general title Aseptic processin

8、g of health care products: Part 1: General requirements Part 2: Filtration Part 3: Lyophilization Part 4: Clean-in-place technologies Part 5: Sterilization in place Part 6: Isolator systems Part 7: Alternative processes for medical devices and combination products The DIN Standards corresponding to

9、the International Standards referred to in this document are as follows: ISO 9000 DIN EN ISO 9000 ISO 9001 DIN EN ISO 9001 ISO 9004 DIN EN ISO 9004 ISO 11135-1 DIN EN ISO 11135-1 ISO 11137-1 DIN EN ISO 11137-1 ISO 11137-2 DIN EN ISO 11137-2 ISO 11137-3 DIN EN ISO 11137-3 ISO 13408-2 DIN EN ISO 13408

10、-2 ISO 13408-3 DIN EN ISO 13408-3 ISO 13408-4 DIN EN ISO 13408-4 ISO 13408-5 DIN EN ISO 13408-5 ISO 13408-6 DIN EN ISO 13408-6 ISO 13485 DIN EN ISO 13485 ISO 14160 DIN EN ISO 14160 ISO 14644-1 DIN EN ISO 14644-1 ISO 14644-2 DIN EN ISO 14644-2 ISO 14644-3 DIN EN ISO 14644-3 ISO 14644-4 DIN EN ISO 146

11、44-4 ISO 14644-5 DIN EN ISO 14644-5 DIN EN ISO 13408-1:2015-12 3 ISO 14644-7 DIN EN ISO 14644-7 ISO 14698-1 DIN EN ISO 14698-1 ISO 14698-2 DIN EN ISO 14698-2 ISO 14937 DIN EN ISO 14937 ISO 14971 DIN EN ISO 14971 ISO 15223 DIN EN ISO 15223 (all parts) ISO 17665-1 DIN EN ISO 17665-1 ISO/TR 14969 DIN-F

12、achbericht CEN ISO/TR 14969 IEC 60812 DIN EN 60812 Amendments This standard differs from DIN EN ISO 13408-1:2013-08 as follows: a) the European Foreword has been updated; b) Annex ZA (informative) “Relationship between this European Standard and the Essential Requirements of EU Directive 90/385/EEC

13、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 medical devices” has been updated; d) Annex ZC (informative) “Relationship between this European Standard and th

14、e Essential Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devices” has been updated. Previous editions DIN EN 13824: 2005-02 DIN EN ISO 13408-1: 2011-09, 2013-08 DIN EN ISO 13408-1:2015-12 4 National Annex NA (informative) Bibliography DIN EN ISO 9000, Quality management syste

15、ms Fundamentals and vocabulary DIN EN ISO 9001, Quality management systems Requirements DIN EN ISO 9004, Managing for the sustained success of an organization A quality management approach DIN EN ISO 11135-1, Sterilization of health care products Ethylene oxide Part 1: Requirements for development,

16、validation and routine control of a sterilization process for medical devices DIN EN 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 DIN EN ISO 11137-2, Sterilization of h

17、ealth care products Radiation Part 2: Establishing the sterilization dose DIN EN ISO 11137-3, Sterilization of health care products Radiation Part 3: Guidance on dosimetric aspects DIN EN ISO 13408-2, Aseptic processing of health care products Part 2: Filtration DIN EN ISO 13408-3, Aseptic processin

18、g of health care products Part 3: Lyophilization DIN EN ISO 13408-4, Aseptic processing of health care products Part 4: Clean-in-place technologies DIN EN ISO 13408-5, Aseptic processing of health care products Part 5: Sterilization in place DIN EN ISO 13408-6, Aseptic processing of health care prod

19、ucts Part 6: Isolator systems DIN EN ISO 13485, Medical devices Quality management systems Requirements for regulatory purposes DIN EN ISO 14160, Sterilization of health care products Liquid chemical sterilizing agents for single-use medical devices utilizing animal tissues and their derivatives Req

20、uirements for characterization, development, validation and routine control of a sterilization process for medical devices DIN EN ISO 14644-1, Cleanrooms and associated controlled environments Part 1: Classification of air cleanliness DIN EN ISO 14644-2, Cleanrooms and associated controlled environm

21、ents Part 2: Specifications for monitoring and periodic testing to prove continued compliance with ISO 14644-1 DIN EN ISO 14644-3, Cleanrooms and associated controlled environments Part 3: Test method DIN EN ISO 14644-4, Cleanrooms and associated controlled environments Part 4: Design, construction

22、and start up DIN EN ISO 14644-5, Cleanrooms and associated controlled environments Part 5: Operations DIN EN ISO 13408-1:2015-12 5 DIN EN ISO 14644-7, Cleanrooms and associated controlled environments Part 7: Separative devices (clean air hoods, gloveboxes, isolators and mini-environments) DIN EN IS

23、O 14698-1, Cleanrooms and associated controlled environments Biocontamination control Part 1: General principles DIN EN ISO 14698-2, Cleanrooms and associated controlled environments Biocontamination control Part 2: Evaluation and interpretation of biocontamination data DIN EN ISO 14937, Sterilizati

24、on of health care products General requirements for characterization of a sterilizing agent and the development, validation and routine control of a sterilization process for medical devices DIN EN ISO 14971, Medical devices Application of risk management to medical devices DIN EN ISO 15223 (all par

25、ts), Medical devices Symbols to be used with medical device labels, labelling and information to be supplied DIN EN ISO 17665-1, Sterilization of health care products Moist heat Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices DIN-Fa

26、chbericht CEN ISO/TR 14969, Medical devices Quality management systems Guidance on the application of ISO 13485:2003 DIN EN 60812, Analysis techniques for system reliability Procedure for failure mode and effects analysis (FMEA) DIN EN ISO 13408-1:2015-12 6 This page is intentionally blank EUROPEAN

27、STANDARD NORME EUROPENNE EUROPISCHE NORM EN ISO 13408-1 June 2015 ICS 11.080.01 Supersedes EN ISO 13408-1:2011English Version Aseptic processing of health care products - Part 1: General requirements (ISO 13408-1:2008, including Amd 1:2013) Traitement aseptique des produits de sant -Partie 1: Exigen

28、ces gnrales(ISO 13408-1:2008, y compris Amd 1:2013) Aseptische Herstellung von Produkten fr die Gesundheitsfrsorge - Teil 1: Allgemeine Anforderungen (ISO 13408-1:2008, einschlielich Amd 1:2013) This European Standard was approved by CEN on 20 May 2015. CEN members are bound to comply with the CEN/C

29、ENELEC 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 references concerning such national standards may be obtained on application to the CEN-CENELEC Management Centr

30、e 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 member into its own language and notified to the CEN-CENELEC Management Centre has the same status as the

31、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, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherla

32、nds, 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: Avenue Marnix 17, B-1000 Brussels 2015 CEN All rights

33、 of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO 13408-1:2015 EContents Page Foreword. 4 Introduction 6 1 Scope . 8 2 Normative references . 8 3 Terms and definitions. 9 4 Quality system elements 14 4.1 General. 14 4.2 Assignment of responsib

34、ilities . 14 4.3 Calibration . 14 5 Aseptic process definition. 15 5.1 General. 15 5.2 Risk management . 15 6 Manufacturing environment 17 6.1 General. 17 6.2 Manufacturing environment design 18 6.3 Layout 19 6.4 Material and personnel flow 21 6.5 HVAC system 22 6.6 Cleanroom qualification. 24 6.7 U

35、tility services and ancillary equipment 24 6.8 Environmental and personnel monitoring programmes 24 7 Equipment . 28 7.1 Qualification 28 7.2 Maintenance of equipment 30 8 Personnel. 30 8.1 General. 30 8.2 Training for APA qualification . 31 8.3 Gowning procedures 32 8.4 General employee health . 33

36、 9 Manufacture of the product . 34 9.1 Attainment and maintenance of sterility 34 9.2 Duration of the manufacturing process . 34 9.3 Aseptic manufacturing procedures 35 9.4 Cleaning and disinfection of facilities 35 9.5 Cleaning, disinfection and sterilization of equipment 37 10 Process simulation.

37、38 10.1 General. 38 10.2 Media selection and growth support 39 10.3 Simulation procedures. 39 10.4 Incubation and inspection of media filled units 40 10.5 Initial performance qualification . 40 10.6 Periodic performance requalification . 41 10.7 Repeat of initial performance qualification 42 10.8 Do

38、cumentation of process simulations . 42 10.9 Disposition of filled product 43 11 Test for sterility. 44 DIN EN ISO 13408-1:2015-12 EN ISO 13408-1:2015 (E) 2 11.1 General . 44 11.2 Investigation of positive units from tests for sterility . 44 Annex A (informative) Example of a flow chart . 45 Annex B

39、 (informative) Typical elements of an aseptic process definition . 46 Annex C (informative) Examples of specific risks 47 Annex D (informative) Comparison of classification of cleanrooms 48 Annex E (informative) Specification for water used in the process 49 Annex F (informative) Aseptic processing

40、area 51 Bibliography . 56 Annex ZA (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 90/385/EEC on active implantable medical devices 52 Annex ZB (informative) Relationship between this European Standard and the Essential Requirements of EU Dire

41、ctive 93/42/EEC on medical devices . 53 Annex ZC (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devices 54 DIN EN ISO 13408-1:2015-12 EN ISO 13408-1:2015 (E) 3 Foreword The text of ISO 13408-1:2008, inc

42、luding Amd 1:2013 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 13408-1:2015 by Technical Committee CEN/TC 204 “Sterilization of medical devices” the secretaria

43、t 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 be withdrawn at the latest by December 2015. Attention is drawn t

44、o 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 13408-1:2011. This document has been prepared under a mandate given to CEN

45、 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 document. The following referenced documents are indispensable for t

46、he 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 standard within the meaning of Annex ZA, ZB or ZC, the user should alway

47、s 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 should be understood as a normative reference to the corresponding EN

48、 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 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 9001 EN ISO 9001:2008 ISO 9001:2008 ISO 11135 EN ISO 11135:2014 ISO 11135:2014 ISO 11137-1