1、English price group 11No 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 11.040.20!%X#“2530061www.din.deDIN EN ISO 836
2、2-5Injection containers and accessories Part 5: Freeze drying closures for injection vials (ISO 8362-5:2016);English version EN ISO 8362-5:2016,English translation of DIN EN ISO 8362-5:2016-07Injektionsbehltnisse und Zubehr Teil 5: Gefriertrocknungsstopfen fr Injektionsflaschen (ISO 8362-5:2016);Eng
3、lische Fassung EN ISO 8362-5:2016,Englische bersetzung von DIN EN ISO 8362-5:2016-07Rcipients et accessoires pour produits injectables Partie 5: Bouchons lyophilisation pour flacons dinjection (ISO 8362-5:2016);Version anglaise EN ISO 8362-5:2016,Traduction anglaise de DIN EN ISO 8362-5:2016-07Super
4、sedesDIN ISO 8362-5:2011-06www.beuth.deDocument comprises 18 pagesDTranslation by DIN-Sprachendienst.In case of doubt, the German-language original shall be considered authoritative.July 201607.16DIN EN ISO 8362-5:2016-07 2 A comma is used as the decimal marker. National foreword This document (EN I
5、SO 8362-5:2016) has been prepared by Technical Committee ISO/TC 76 “Transfusion, infusion and injection, and blood processing equipment for medical and pharmaceutical use” in collaboration with Technical Committee CEN/TC 205 “Non-active medical devices” (Secretariat: DIN, Germany). The responsible G
6、erman body involved in its preparation was DIN-Normenausschuss Medizin (DIN Standards Committee Medicine), Working Committee NA 063-02-15 AA Elastomere Pharmapackmittel und zugehrige Komponenten. DIN EN ISO 8362-5, Injection containers and accessories consists of the following parts: Part 1: Injecti
7、on vials made of glass tubing Part 2: Closures for injection vials Part 3: Aluminium caps for injection vials Part 4: Injection vials made of moulded glass Part 5: Freeze drying closures for injection vials Part 6: Caps made of aluminium-plastics combinations for injection vials Part 7: Injections c
8、aps made of aluminium-plastics combinations without overlapping plastics parts The DIN Standards corresponding to the International Standards referred to in this document are as follows: ISO 48 DIN ISO 48 ISO 7619-1 DIN ISO 7619-1 ISO 8871-1 DIN EN ISO 8871-1 ISO 8871-4 DIN EN ISO 8871-4 ISO 8871-5
9、DIN EN ISO 8871-5 ISO 15378 DIN EN ISO 15378 Amendments This standard differs from DIN ISO 8362-5:2011-06 as follows: a) particulate contamination requirements have been specified; b) the standard has been editorially revised; c) the ISO standard has been adopted as a European standard. Previous edi
10、tions DIN 58359: 1980-09 DIN ISO 8362-5: 1996-07, 2011-06 DIN EN ISO 8362-5:2016-07 3 National Annex NA (informative) Bibliography DIN ISO 48, Rubber, vulcanized or thermoplastic Determination of hardness (hardness between 10 IRHD and 100 IRHD) DIN ISO 7619-1, Rubber, vulcanized or thermoplastic Det
11、ermination of indentation hardness Part 1: Durometer method (Shore hardness) DIN EN ISO 8871-1, Elastomeric parts for parenterals and for devices for pharmaceutical use Part 1: Extractables in aqueous autoclavates DIN EN ISO 8871-4, Elastomeric parts for parenterals and for devices for pharmaceutica
12、l use Part 4: Biological requirements and test methods DIN EN ISO 8871-5, Elastomeric parts for parenterals and for devices for pharmaceutical use Part 5: Functional requirements and testing DIN EN ISO 15378, Primary packaging materials for medicinal products Particular requirements for the applicat
13、ion of ISO 9001:2008, with reference to Good Manufacturing Practice (GMP) DIN EN ISO 8362-5:2016-07 4 This page is intentionally blank EUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NORM EN ISO 8362-5 March 2016 ICS 11.040.20 English Version Injection containers and accessories Part 5: Freeze drying c
14、losures for injection vials (ISO 8362-5:2016) Rcipients et accessoires pour produits injectables Partie 5: Bouchons lyophilisation pour flacons dinjection (ISO 8362-5:2016) Injektionsbehltnisse und Zubehr Teil 5: Gefriertrocknungsstopfen fr Injektionsflaschen (ISO 8362-5:2016) This European Standard
15、 was approved by CEN on 2 January 2016. 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 bibliographical references concerning such
16、 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 responsibility of a CEN member into its own
17、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, Former Yugoslav Republic of Macedonia, France, Germany, Gr
18、eece, Hungary, Iceland, 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 NORMUN
19、G CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels 2016 CEN All rights of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO 8362-5:2016 E EN ISO 8362-5:2016 (E) 2 Contents Page DIN EN ISO 8362-5:2016-07 European foreword . 3 Forewo
20、rd 4 Introduction 5 1 Scope 6 2 Normative references 6 3 Terms and definitions . 6 4 Shape and dimensions . 7 5 Designation 9 6 Material . 9 7 Performance requirements . 9 7.1 General 9 7.2 Physical requirements 9 7.2.1 Hardness . 9 7.2.2 Penetrability . 9 7.2.3 Fragmentation 9 7.2.4 Self-sealing an
21、d aqueous solution tightness 10 7.2.5 Aqueous solution tightness 10 7.2.6 Resistance to ageing 10 7.2.7 Residual moisture 10 7.3 Chemical requirements 10 7.4 Biological requirements 10 7.5 Particulate contamination requirements . 10 8 Labelling 10 Annex A (informative) Determination of moisture . 11
22、 A.1 Principle 11 A.2 Apparatus 11 A.3 Reagents 11 A.4 Procedure 11 A.4.1 Apparatus preparation 11 A.4.2 Sample preparation . 12 A.4.3 Determination . 12 A.5 Calculation and expression of results . 12 A.5.1 Extrapolation . 12 A.5.2 Expression of results . 13 A.6 Comments and limitations 13 Bibliogra
23、phy . 14 EN ISO 8362-5:2016 (E) 3 European foreword This document (EN ISO 8362-5:2016) has been prepared by Technical Committee ISO/TC 76 “Transfusion, infusion and injection, and blood processing equipment for medical and pharmaceutical use” in collaboration with Technical Committee CEN/TC 205 “Non
24、-active medical devices” the secretariat of which is held by DIN. 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 September 2016, and conflicting national standards shall be withdrawn at the lates
25、t by September 2016. 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. According to the CEN-CENELEC Internal Regulations, the national s
26、tandards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania
27、, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom. Endorsement notice The text of ISO 8362-5:2016 has been approved by CEN as EN ISO 8362-5:2016 without any modification. DIN EN ISO 8362-5:2016-07 Forewo
28、rdISO (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 for which a technica
29、l 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 all matters of ele
30、ctrotechnical standardization.The procedures used to develop this document and those intended for its further maintenance are described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the different types of ISO documents should be noted. This document was
31、drafted in accordance with the editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).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
32、 rights. Details of any patent rights identified during the development of the document will be in the Introduction and/or on the ISO list of patent declarations received (see www.iso.org/patents).Any trade name used in this document is information given for the convenience of users and does not con
33、stitute an endorsement.For an explanation on the meaning of ISO specific terms and expressions related to conformity assessment, as well as information about ISOs adherence to the WTO principles in the Technical Barriers to Trade (TBT) see the following URL: Foreword - Supplementary information.The
34、committee responsible for this document is ISO/TC 76, Transfusion, infusion and injection, and blood processing equipment for medical and pharmaceutical use.This third edition cancels and replaces the second edition (ISO 8362-5:2008), which has been technically revised to include a new 7.5.ISO 8362
35、consists of the following parts, under the general title Injection containers and accessories: Part 1: Injection vials made of glass tubing Part 2: Closures for injection vials Part 3: Aluminium caps for injection vials Part 4: Injection vials made of moulded glass Part 5: Freeze drying closures for
36、 injection vials Part 6: Caps made of aluminium-plastics combinations for injection vials Part 7: Injection caps made of aluminium-plastics combinations without overlapping plastics partEN ISO 8362-5:2016 (E) 4DIN EN ISO 8362-5:2016-07 IntroductionFreeze drying closures are put on the top of a glass
37、 container after filling, leaving sufficient openings for the sublimation process and vacuum. At the end of the drying process, they are fully inserted into the glass container by hydraulic or mechanical means in the vacuum chamber.Freeze drying closures can pick up water during shipping, storage, w
38、ashing and steam sterilization cycles, which is difficult to remove in a subsequent drying cycle. As a consequence, the freeze drying closures are usually loaded with residual moisture. Depending upon the mass of the freeze-dried product and the degree of its sensitivity to water, the residual moist
39、ure in the rubber material can spoil the freeze-dried preparation during storage.These specific process requirements have been addressed in this part of ISO 8362 by specifying relevant requirements for freeze drying closures, including a test method for determining residual moisture.Primary packagin
40、g components made of elastomeric materials are an integral part of medicinal products and thus the principles of current Good Manufacturing Practices (cGMP) apply to the manufacturing of these components.Principles of cGMP are described, for instance, in ISO 15378 or in the GMP Guidelines as publish
41、ed by the European Community and the United States of America.EN ISO 8362-5:2016 (E) 5DIN EN ISO 8362-5:2016-07 1 ScopeThis part of ISO 8362 specifies the shape, dimensions, material, performance requirements and labelling for the type of closure for injection vials, as described in ISO 8362-1 and I
42、SO 8362-4, which is used in connection with the freeze drying (or lyophilization) of drugs and biological materials.The dimensional requirements are not applicable to barrier-coated closures.Closures specified in this part of ISO 8362 are intended for single use only.NOTE The potency, purity, stabil
43、ity and safety of a medicinal product during its manufacture and storage can be strongly affected by the nature and performance of the primary packaging.2 Normative referencesThe following documents, in whole or in part, are normatively referenced in this document and are indispensable for its appli
44、cation. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies.ISO 48, Rubber, vulcanized or thermoplastic Determination of hardness (hardness between 10 IRHD and 100 IRHD)ISO 33021, Rubber Tolera
45、nces for products Part 1: Dimensional tolerancesISO 33022, Rubber Tolerances for products Part 2: Geometrical tolerancesISO 76191, Rubber, vulcanized or thermoplastic Determination of indentation hardness Part 1: Durometer method (Shore hardness)ISO 88711, Elastomeric parts for parenterals and for d
46、evices for pharmaceutical use Part 1: Extractables in aqueous autoclavatesISO 88714, Elastomeric parts for parenterals and for devices for pharmaceutical use Part 4: Biological requirements and test methodsISO 88715:2005, Elastomeric parts for parenterals and for devices for pharmaceutical use Part
47、5: Functional requirements and testing3 Terms and definitionsFor the purposes of this document, the following terms and definitions apply.3.1freeze dryinglyophilizationdrying process designed to remove solvents from both aqueous and non-aqueous systems by sublimation and desorptionEN ISO 8362-5:2016
48、 (E) 6DIN EN ISO 8362-5:2016-07 3.2freeze drying closureclosure that enables the drying of a frozen pharmaceutical preparation in a vacuum chamber4 Shape and dimensions4.1 The dimensions of freeze drying closures shall be given in Table 1 while Figure 1 illustrates the general design of a freeze dry
49、ing closure.Table 1 Dimensions of freeze drying closuresDimensions in millimetresNominal sized10,2d2amin.h20,25h3min.h4min.13 12,5 7, 5 2,0 2,0 1,820 18,8 13,0 3,3 2,0 2,0aThe value of d2 is applied in that area which is defined by h3.4.2 If not otherwise specified, general dimensional tolerances shall be in accordance with ISO 3302-1 and ISO 3302-2.4.3 If spacers are located on the top of the flange, they shall not interfere with the marks for the piercing area (see Figure 1). The heig
