1、BSI Standards PublicationBS EN ISO 8362-5:2016Injection containers and accessoriesPart 5: Freeze drying closures for injection vials BS EN ISO 8362-5:2016 BRITISH STANDARDNational forewordThis British Standard is the UK implementation of EN ISO 8362-5:2016.The UK participation in its preparation was
2、 entrusted to Technical Committee CH/212, IVDs.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. The British Sta
3、ndards Institution 2016.Published by BSI Standards Limited 2016ISBN 978 0 580 87254 9 ICS 11.040.20 Compliance with 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 31 March 2016
4、.Amendments/corrigenda issued since publicationDate T e x t a f f e c t e dEUROPEAN 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 closures for injection vials (ISO 8362-5:2016) Rcipients et
5、 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 was approved by CEN on 2 January 2016. CEN members ar
6、e 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 national standards may be obtained on application to
7、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 language and notified to the CEN-CENELEC Management Ce
8、ntre 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, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithua
9、nia, 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 Management Centre: Avenue Marnix 17, B-1
10、000 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 EBS EN ISO 8362-5:2016EN ISO 8362-5:2016 (E) 3 European foreword This document (EN ISO 8362-5:2016) has been prepared by Technical Committee ISO/TC 7
11、6 “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” the secretariat of which is held by DIN. This European Standard shall be given the status of a national standar
12、d, 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 latest by September 2016. Attention is drawn to the possibility that some of the elements of this document may be the subject of patent right
13、s. 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 countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cy
14、prus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the Unit
15、ed Kingdom. Endorsement notice The text of ISO 8362-5:2016 has been approved by CEN as EN ISO 8362-5:2016 without any modification. BS EN ISO 8362-5:2016ISO 8362-5:2016(E)Foreword ivIntroduction v1 Scope . 12 Normative references 13 Terms and definitions . 14 Shape and dimensions 25 Designation 46 M
16、aterial 47 Performance requirements . 47.1 General . 47.2 Physical requirements 47.2.1 Hardness . 47.2.2 Penetrability 47.2.3 Fragmentation 47.2.4 Self-sealing and aqueous solution tightness 57.2.5 Aqueous solution tightness 57.2.6 Resistance to ageing 57.2.7 Residual moisture . 57.3 Chemical requir
17、ements 57.4 Biological requirements 57.5 Particulate contamination requirements . 58 Labelling 5Annex A (informative) Determination of moisture . 6Bibliography 9 ISO 2016 All rights reserved iiiContents PageBS EN ISO 8362-5:2016ISO 8362-5:2016(E)ForewordISO (the International Organization for Standa
18、rdization) 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 the right t
19、o 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.The procedures use
20、d 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 drafted in accordance with the editorial rules o
21、f 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 rights. Details of any patent rights identified
22、 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 constitute an endorsement.For an explanation on the
23、 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 committee responsible for this document is ISO/T
24、C 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 consists of the following parts, under the gener
25、al 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 injection vials Part 6: Caps made of aluminium-
26、plastics combinations for injection vials Part 7: Injection caps made of aluminium-plastics combinations without overlapping plastics partiv ISO 2016 All rights reservedBS EN ISO 8362-5:2016ISO 8362-5:2016(E)IntroductionFreeze drying closures are put on the top of a glass container after filling, le
27、aving 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, washing and steam sterilizati
28、on 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 moisture in the rubber material c
29、an 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 packaging components made of elastom
30、eric 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 published by the European Community
31、 and the United States of America. ISO 2016 All rights reserved vBS EN ISO 8362-5:2016BS EN ISO 8362-5:2016Injection containers and accessories Part 5: Freeze drying closures for injection vials1 ScopeThis part of ISO 8362 specifies the shape, dimensions, material, performance requirements and label
32、ling for the type of closure for injection vials, as described in ISO 8362-1 and ISO 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
33、part of ISO 8362 are intended for single use only.NOTE The potency, purity, stability 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 par
34、t, are normatively referenced in this document and are indispensable for its application. 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 Determi
35、nation of hardness (hardness between 10 IRHD and 100 IRHD)ISO 33021, Rubber Tolerances 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: Durom
36、eter method (Shore hardness)ISO 88711, Elastomeric parts for parenterals and for devices 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 88715:20
37、05, Elastomeric parts for parenterals and for devices for pharmaceutical use Part 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 bo
38、th aqueous and non-aqueous systems by sublimation and desorptionINTERNATIONAL STANDARD ISO 8362-5:2016(E) ISO 2016 All rights reserved 1BS EN ISO 8362-5:2016ISO 8362-5:2016(E)3.2freeze drying closureclosure that enables the drying of a frozen pharmaceutical preparation in a vacuum chamber4 Shape and
39、 dimensions4.1 The dimensions of freeze drying closures shall be given in Table 1 while Figure 1 illustrates the general design of a freeze drying 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
40、,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 pier
41、cing area (see Figure 1). The height of the spacers shall not exceed 0,3 mm.NOTE The spacers in Figure 1 are shown for illustrative purposes only and do not form part of the requirements of this part of ISO 8362.There may be marks or indentations on the top surface.4.4 If the flange of the closure h
42、as a slightly conical shape, it shall be 0,3 mm maximum in relation to the diameter in order to facilitate production. The tolerances of the trimming edge of the flange shall comply with the tolerances specified in Table 1 for diameter d1.4.5 The plug part shall provide slits, channels or other appr
43、opriate means, in conjunction with protruding or positioning elements at the outer diameter, which enable insertion on a drying (halfway) position during the sublimation process.4.6 The design of the positioning element to hold the freeze drying closure firmly in the sublimation position should not
44、compromise the full insertion of the closure into the neck of the vial.4.7 The design of the flange part in conjunction with the plug design shall permit both the reconstitution of the freeze-dried product with the appropriate solvent and the removal of the dissolved product by means of a piercing d
45、evice.2 ISO 2016 All rights reservedBS EN ISO 8362-5:2016ISO 8362-5:2016(E)Dimensions in millimetresAA1120,7hhhhddaKey1 positioning element2 spaceraThe inner diameter shall not be wider than the inner lumen.NOTE The total height of the freeze drying closure, h1, can vary and is subject to mutual agr
46、eement between manufacturer and user.Figure 1 Example of a freeze drying closure design4.8 The freeze drying closure shall be designed and manufactured in such a way that the removal of the reconstituted product with a hypodermic needle can be visually controlled in order to minimize the amount of r
47、esidual product. ISO 2016 All rights reserved 3BS EN ISO 8362-5:2016ISO 8362-5:2016(E)4.9 When freeze drying closures are put in place for the lyophilization process and the container is exposed to transportation processes, they should exhibit sufficient shock and vibration resistance that, under re
48、gular processing conditions, they do not fall off or become distorted.5 DesignationA freeze drying closure for injection vials can be designated by the words “freeze drying closure” followed by the number of this part of ISO 8362 followed by the nominal size.EXAMPLE A freeze drying closure of nomina
49、l size 13 complying with the requirements laid down in this part of ISO 8362 is designated as follows:Freeze drying closure ISO 83625 136 MaterialThe elastomeric material used shall meet the requirements specified in Clause 7.The elastomeric material shall withstand two sterilization cycles when autoclaving in saturated steam at (121 2) C for 30 min without exceeding the specified limits and without impairment of its performance characteristics under conditions of normal use. In case other sterilizati
