1、raising standards worldwideNO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAWBSI Standards PublicationBS EN ISO 13408-3:2011Aseptic processing of healthcare productsPart 3: Lyophilization (ISO 13408-3:2006)BS EN ISO 13408-3:2011 BRITISH STANDARDNational forewordThis British Stand
2、ard is the UK implementation of EN ISO 13408-3:2011. It is identical to ISO 13408-3:2006. Together with the other parts of the BS EN ISO 13408 series, it supersedes BS EN 13824:2004.The UK participation in its preparation was entrusted to Technical Committee CH/198, Sterilization of medical devices.
3、A list of organizations represented on this committee can be obtained on request to its secretary.This publication does not purport to include all the necessary provisions of a contract. Users are responsible for its correct application. BSI 2011 ISBN 978 0 580 72610 1 ICS 11.080.01 Compliance with
4、a British Standard cannot confer immunity from legal obligations.This British Standard was published under the authority of the Standards Policy and Strategy Committee on 30 October 2011.Amendments issued since publicationDate Text affectedEUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NORM EN ISO 134
5、08-3 June 2011 ICS 11.080.01 Supersedes EN 13824:2004English Version Aseptic processing of health care products - Part 3: Lyophilization (ISO 13408-3:2006) Traitement aseptique des produits de sant - Partie 3: Lyophilisation (ISO 13408-3:2006) Aseptische Herstellung von Produkten fr die Gesundheitsf
6、rsorge - Teil 3: Gefriertrocknung (ISO 13408-3:2006) 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 al
7、teration. Up-to-date lists and 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 m
8、ade 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 official versions. CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Est
9、onia, Finland, France, Germany, 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 EUR
10、OPISCHES KOMITEE FR NORMUNG Management 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 13408-3:2011: EBS EN ISO 13408-3:2011 EN ISO 13408-3:2011 (E) 3 Foreword The text of ISO 1340
11、8-3:2006 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 13408-3:2011 by Technical Committee CEN/TC 204 “Sterilization of medical devices” the secretariat of whic
12、h 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. Attention is drawn to the pos
13、sibility 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 mandate given to CEN by the Europea
14、n 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 Regulations, the national standards
15、 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, Malta, Netherlands, Norway, Polan
16、d, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 13408-3:2006 has been approved by CEN as a EN ISO 13408-3:2011 without any modification. BS EN ISO 13408-3:2011EN ISO 13408-3:2011 (E) 4 Annex ZA (informative) Relationship
17、 between this European Standard and the Essential Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices This European Standard has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association to provide a means of conforming to
18、 Essential Requirements of the New Approach Directive 90/385/EEC on active implantable medical devices. Once this standard is cited in the Official Journal of the European Union under that Directive and has been implemented as a national standard in at least one Member State, compliance with the cla
19、uses of this standard given in Table ZA.1 confers, within the limits of the scope of this standard, a presumption of conformity with the corresponding Essential Requirements of that Directive and associated EFTA regulations. Table ZA.1 Correspondence between this European Standard and Directive 90/3
20、85/EEC Clauses of this EN Essential Requirements (ERs) of Directive 90/385/EEC Qualifying remarks/Notes 4,5,6,7,8,9 7 This relevant Essential Requirement is only partly addressed in this European Standard and only in conjunction with EN ISO 13408-1 WARNING Other requirements and other EU Directives
21、may be applicable to the product(s) falling within the scope of this Standard. BS EN ISO 13408-3:2011 EN ISO 13408-3:2011 (E) 5 Annex ZB (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 93/42/EEC on Medical Devices This European Standard has be
22、en prepared under a mandate given to CEN by the European Commission and the European Free Trade Association to provide a means of conforming to Essential Requirements of the New Approach Directive 93/42/EEC on medical devices. Once this standard is cited in the Official Journal of the European Union
23、 under that Directive and has been implemented as a national standard in at least one Member State, compliance with the clauses of this standard given in Table ZB.1 confers, within the limits of the scope of this standard, a presumption of conformity with the corresponding Essential Requirements of
24、that Directive and associated EFTA regulations. Table ZB.1 Correspondence between this European Standard and Directive 93/42/EEC Clauses of this EN Essential Requirements (ERs) of Directive 93/42/EEC Qualifying remarks/Notes 4,5,6,7,8,9 8.3 This relevant Essential Requirement is only partly addresse
25、d in this European Standard and only in conjunction with EN ISO 13408-1 4,5,6,7,8,9 8.4 This relevant Essential Requirement is addressed in this European standard only in conjunction with EN ISO 13408-1 WARNING Other requirements and other EU Directives may be applicable to the product(s) falling wi
26、thin the scope of this Standard. BS EN ISO 13408-3:2011EN ISO 13408-3:2011 (E) 6 Annex ZC (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devices This European Standard has been prepared under a mandate
27、given to CEN by the European Commission and the European Free Trade Association to provide a means of conforming to Essential Requirements of the New Approach Directive 98/79/EC on in vitro diagnostic medical devices. Once this standard is cited in the Official Journal of the European Union under th
28、at Directive and has been implemented as a national standard in at least one Member State, compliance with the clauses of this standard given in Table ZC.1 confers, within the limits of the scope of this standard, a presumption of conformity with the corresponding Essential Requirements of that Dire
29、ctive and associated EFTA regulations. Table ZC.1 Correspondence between this European Standard and Directive 98/79/EC Clauses of this EN Essential Requirements (ERs) of Directive 98/79/EC Qualifying remarks/Notes 4,5,6,7,8,9 B.2.3 This relevant Essential Requirement is only partly addressed in this
30、 European Standard and only in conjunction with EN ISO 13408-1 4,5,6,7,8,9 B.2.4 This relevant Essential Requirement is addressed in this European standard only in conjunction with EN ISO 13408-1 WARNING Other requirements and other EU Directives may be applicable to the product(s) falling within th
31、e scope of this Standard. BS EN ISO 13408-3:2011ISO 13408-3:2006(E) ISO 2006 All rights reserved iiiContents Page Foreword iv Introduction v 1 Scope . 1 2 Normative references . 1 3 Terms and definitions. 1 4 Quality system elements 1 4.1 General. 1 4.2 Management responsibility . 2 4.3 Design contr
32、ol. 2 4.4 Measuring instruments and/or measuring systems . 2 5 Product definition . 2 6 Process definitions. 2 7 User requirements 3 7.1 General. 3 7.2 Equipment characterization. 3 7.3 Product handling 4 7.4 Microbiological and particulate environmental monitoring . 4 7.5 Cleaning and sterilization
33、 4 7.6 Vent filter system 5 7.7 Lyophilizer leak test 5 8 Validation. 5 8.1 General. 5 8.2 Design qualification 6 8.3 Installation qualification. 6 8.4 Operational qualification 6 8.5 Performance qualification 8 8.6 Process validation 8 8.7 Review and approval of validation 9 9 Routine monitoring an
34、d control 9 9.1 General. 9 9.2 Operator training. 9 9.3 Standard operating procedures 9 9.4 Requalification 10 9.5 Maintenance of equipment 10 9.6 Change control 10 Bibliography . 11 BS EN ISO 13408-3:2011ISO 13408-3:2006(E) iv ISO 2006 All rights reservedForeword ISO (the International Organization
35、 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 established has
36、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 standardization. Intern
37、ational 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. Publicati
38、on as an International Standard requires approval by at least 75 % of the member bodies casting a vote. Attention is drawn to the possibility 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 right
39、s. ISO 13408-3 was prepared by Technical Committee ISO/TC 198, Sterilization of health care products. 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 Part 4: Clean-in
40、-place technologies Part 5: Sterilization in place Part 6: Isolator systems BS EN ISO 13408-3:2011ISO 13408-3:2006(E) ISO 2006 All rights reserved vIntroduction This part of ISO 13408 deals with lyophilization, which is a physical-chemical drying process designed to remove solvents from both aqueous
41、 and non-aqueous systems, primarily to achieve product or material stability. Lyophilization is synonymous to the term freeze-drying. Lyophilization involves freezing an aqueous system and removing the solvent, first by sublimation (primary drying) and then by desorption (secondary drying), to a lev
42、el that no longer supports chemical reactions or biological growth. The result is a stable, well-formed product meant to rapidly disperse or solubilize while retaining biological or other activity. Because it is often the final step in an aseptic process with direct impact on the safety, quality, id
43、entity, potency and purity of a product, lyophilization is a critical processing step. Where the finished lyophilized product is intended to be sterile, the product to be dried is an aqueous system that has already been sterilized. Therefore, all activities that can affect the sterility of the produ
44、ct or material need to be regarded as extensions of the aseptic processing of that sterilized product or material. In general, the predominant challenge in ensuring product or material sterility during lyophilization is to prevent microbiological and particulate contamination between the filling ope
45、ration and completion of the lyophilization process. Of special, equipment-related concern is the protection of the product or material from microbiological contamination within the chamber. BS EN ISO 13408-3:2011BS EN ISO 13408-3:2011INTERNATIONAL STANDARD ISO 13408-3:2006(E) ISO 2006 All rights re
46、served 1Aseptic processing of health care products Part 3: Lyophilization 1 Scope This part of ISO 13408 specifies requirements for, and offers guidance on, equipment, processes, programmes and procedures for the control and validation of lyophilization as an aseptic process. It does not address the
47、 physical/chemical objectives of a lyophilization process. 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 (in
48、cluding any amendments) applies. ISO 9001, Quality management systems Requirements ISO 13408-1, Aseptic processing of health care products Part 1: General requirements ISO 13408-4, Aseptic processing of health care products Part 4: Clean-in-place technologies ISO 13408-5, Aseptic processing of healt
49、h care products Part 5: Sterilization in place 3 Terms and definitions For the purposes of this document, the terms and definitions given in ISO 13408-1 and the following apply. 3.1 lyophilization physical-chemical drying process designed to remove solvents from both aqueous and non-aqueous systems, by sublimation and desorption 3.2 leak test physical test for the capability to provide a quantifiable leakage rate under repeatable test conditions 4 Quality system elements 4.1 General 4.1.1 The requirements of ISO 13408-1 shall appl
