1、December 2013 Translation by DIN-Sprachendienst.English price group 8No 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).IC
2、S 11.040.25!%*OM“2074442www.din.deDDIN ISO 11040-5Prefilled syringes Part 5: Plunger stoppers for injectables (ISO 11040-5:2012),English translation of DIN ISO 11040-5:2013-12Vorgefllte Spritzen Teil 5: Kolbenstopfen fr Injektionsprparate (ISO 11040-5:2012),Englische bersetzung von DIN ISO 11040-5:2
3、013-12Seringues prremplies Partie 5: Bouchons-pistons pour produits injectables (ISO 11040-5:2012),Traduction anglaise de DIN ISO 11040-5:2013-12SupersedesDIN ISO 11040-5:2003-03www.beuth.deDocument comprises pagesIn case of doubt, the German-language original shall be considered authoritative.1111.
4、13 DIN ISO 11040-5:2013-12 A comma is used as the decimal marker. Contents Page National foreword .3 National Annex NA (informative) Bibliography 5 Introduction .6 1 Scope 7 2 Normative references 7 3 Classification 7 4 Shape and dimensions 7 5 Designation 9 6 Material .10 7 Requirements .10 7.1 Gen
5、eral 10 7.2 Physical requirements 10 7.2.1 Hardness .10 7.2.2 Resistance to ageing .10 7.3 Chemical requirements .10 7.4 Biological requirements 10 8 Labelling .10 Bibliography 11 2 DIN ISO 11040-5:2013-12 National foreword This document (ISO 11040-5:2012) has been prepared by Technical Committee IS
6、O/TC 76 “Transfusion, infusion and injection, and blood processing equipment for medical and pharmaceutical use” (Secretariat: DIN, Germany). The responsible German body involved in its preparation was the Normenausschuss Medizin (Medical Standards Committee), Working Committee NA 063-02-15 AA Elast
7、omere Pharmapackmittel und zugehrige Komponenten. Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. DIN and/or DKE shall not be held responsible for identifying any or all such patent rights. It should be noted that this standard in
8、cludes two National footnotes referring to other parts of this standard and one to explain an abbreviation in the English reference version. The DIN Standards corresponding to the International Standards referred to in this document are as follows: ISO 48 DIN ISO 48 ISO 3302-1 DIN ISO 3302-1 ISO 330
9、2-2 DIN ISO 3302-2 ISO 7619-1 DIN ISO 7619-1 ISO 8362-5 DIN ISO 8362-5 ISO 8871-1 DIN EN ISO 8871-1 ISO 8871-4 DIN EN ISO 8871-4 ISO 9997 DIN EN ISO 9997 ISO 11040-4 DIN ISO 11040-4 ISO 15378 DIN EN ISO 15378 DIN ISO 11040 consists of the following parts, under the general title Prefilled syringes:
10、Part 1: Glass cylinders for dental local anaesthetic cartridges Part 2: Plunger stoppers for dental local anaesthetic cartridges Part 3: Aluminium caps for dental local anaesthetic cartridges Part 4: Glass barrels for injectablesN1) Part 5: Plunger stoppers for injectables Part 6: Plastics barrels f
11、or injectablesN2) Part 7: Packaging systems for prefillable ready-to-use syingesN2)N1) National footnote: This part of the standards series is currently under revision. N2) National footnote: This part of the standards series is currently in preparation. 3 DIN ISO 11040-5:2013-12 4 Amendments This s
12、tandard differs from DIN ISO 11040-5:2003-03 as follows: a) the title of this part of ISO 11040 has been adjusted; b) this International Standard has been brought in line with the ISO 8871 series; c) the requirements on the height of the spacers and on material and hardness of the plunger stoppers h
13、ave been revised; d) Table 1 “Dimensions of plunger stoppers” has been supplemented by the missing value of the nominal dimensions of h1(13,45 up to 13,50) with d2(19,05 0,2); e) requirements on resistance to ageing have been added; f) in the German version, the translation of PSL has been adjusted
14、to the new spelling in ISO 11040-5; g) the standard has been editorially revised. Previous editions DIN 58358-5: 1992-11 DIN ISO 11040-5: 1996-08, 2003-03 DIN ISO 11040-5:2013-12 National Annex NA (informative) Bibliography DIN ISO 48, Rubber, vulcanized or thermoplastic Determination of hardness (h
15、ardness between 10 IRHD and 100 IRHD) DIN ISO 3302 (all parts), Rubber Tolerances for products DIN ISO 7619-1, Rubber, vulcanized or thermoplastic Determination of indentation hardness Part 1: Durometer method (Shore hardness) DIN ISO 8362-5, Injection containers and accessories Part 5: Freeze dryin
16、g closures for injection vials 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 pharmaceutical use Part 4: Biological requirements and test
17、 methods DIN EN ISO 9997, Dental cartridge syringes DIN EN ISO 15378, Primary packaging materials for medicinal products Particular requirements for the application of ISO 9001:2008, with reference to Good Manufacturing Practice (GMP) DIN ISO 11040-4, Prefilled syringes Part 4: Glass barrels for inj
18、ectables 5 Introduction Primary packaging components made of elastomeric materials are an integral part of medicinal products. Therefore, the principles of current good manufacturing practices (cGMPN3) apply to the manufacturing of these components. Principles of cGMP are described in e.g. ISO 15378
19、 or in the GMP Guidelines published by the European Community and the United States of America. N3) National footnote: cGMP, en: current Good Manufacturing PracticeDIN ISO 11040-5:2013-12 6 Prefilled syringes Part 5: Plunger stoppers for injectables 1 ScopeThis part of ISO 11040 specifies the shape,
20、 dimensions, material, performance requirements and labelling of plunger stoppers for glass barrels (single-chamber design) for injection preparations in accordance with ISO 11040-4.Plunger stoppers specified in this part of ISO 11040 are intended for single use only.This part of ISO 11040 is not ap
21、plicable to barrier-coated plunger stoppers.NOTE The potency, purity, stability and safety of a medicinal product during its manufacture and storage can be significantly affected by the nature and performance of the primary packaging.2 Normative referencesThe following referenced documents are indis
22、pensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies.ISO 3302-1, Rubber Tolerances for products Part 1: Dimensional tolerancesISO 7619-1, Rubber, v
23、ulcanized or thermoplastic Determination of indentation hardness Part 1: Durometer method (Shore hardness)ISO 8871-1, Elastomeric parts for parenterals and for devices for pharmaceutical use Part 1: Extractables in aqueous autoclavatesISO 8871-4, Elastomeric parts for parenterals and for devices for
24、 pharmaceutical use Part 4: Biological requirements and test methodsISO 11040-4, Prefilled syringes Part 4: Glass barrels for injectables3 ClassificationPlunger stoppers shall be classified as follows: type PSL: plunger stoppers with snap lid; type PST: plunger stoppers with thread.4 Shape and dimen
25、sions4.1 The shape and dimensions of plunger stoppers shall be as shown in Figure 1 and given in Table 1.DIN ISO 11040-5:2013-12 7 Dimensions in millimetresa) Plunger stopper with snap lid (PSL)NOTE Thread: 16 pitch on 25,4 mm; for 1 ml (long), 17 pitch on 25,4 mm.b) Plunger stopper with thread (PST
26、)Shape and dimensions of plunger stoppers for a prefilled syringeDIN ISO 11040-5:2013-12 8 Dimensions of plunger stoppersDimensions in millimetresNominal inner diameterNominal volumeType d1ad2ad3ah1ah2ad2bml nom. tol. nom. tol. nom. tol. nom. tol. nom. tol.4,65 0,1 0,5 PSL5,2 to 5,30,14,1 to 4,20,15
27、2,50,26,85 to 7,00,45,3 0,356,35 0,1 1 (long)PST6,8 to 75,9 to 62,67,65 to 7,854,50,38,65 0,2 1 to 39,05 to 9,257,6 to 84,77,7 to 7,85411,85 0,2 512,5 to 12,710,5 to 11,155,2 to 5,60,258,5 6,014,25 0,2 1015 to 15,313,5 to 13,757,4 to 7,68,5 to 106 to 6,219,05 0,2 2019,9 to 20,10,1518,4 to 18,610,713
28、,45 to 13,507aThe nominal diameter shall be agreed upon between the manufacturer and the user within the given range.bIn accordance with ISO 11040-4.4.2 If not otherwise specified, general dimensional tolerances shall be Class M3 in accordance with ISO 3302-1.4.3 In order to prevent the plunger stop
29、pers from adhering to each other, there shall be spacers. The height of the spacers shall not exceed 0,3 mm.The shape of the spacers should be agreed upon between the manufacturer and the cartridge assembler.4.4 Sprues, if present on the surface of the plunger stopper, shall not protrude beyond the
30、surface of the plunger stopper.4.5 The performance and dimensions of the plunger stopper thread shall be compatible with the plunger rod. The plunger stopper shall not detach itself from the rod under normal use, e.g. aspiration.5 DesignationPlunger stoppers are designated according to their type. T
31、he designation shall comprise, in the following order, the descriptor “Plunger”, a reference to this part of ISO 11040, the type of plunger snap lip (PSL) or threaded (PST), the volume of the barrel for which the plunger stopper is intended, and the letters “lg” if it is the long version.EXAMPLE 1 D
32、esignation of a plunger stopper with snap lip for a glass barrel of 0,5 ml nominal volume, complying with the requirements in this part of ISO 11040:Plunger ISO 11040-5 - PSL - 0,5EXAMPLE 2 Designation of a threaded plunger stopper for a glass barrel of 1 ml nominal volume, long version, complying w
33、ith the requirements in this part of ISO 11040:Plunger ISO 11040-5 - PST - 1 - lgDIN ISO 11040-5:2013-12 9 6 MaterialThe elastomeric material used shall meet the requirements specified in Clause 7.Plunger stoppers shall be made from the elastomeric formulation originally tested and approved by the e
34、nd user. The manufacturer of the plunger stopper shall ensure the conformance of each delivery with the type sample and compliance with previously agreed functional and compendial requirements.The elastomeric material shall withstand two sterilization cycles when autoclaving in saturated steam at (1
35、21 2) C for 30 min without impairment of its function under conditions of normal use. If other sterilization methods are used, e.g. irradiation, the suitability of the material shall be evaluated.7 Requirements7.1 GeneralThe requirements specified in 7.2 to 7.4 constitute minimum requirements concer
36、ning the condition of the elastomeric plunger stopper on receipt by the user.7.2 Physical requirements7.2.1 HardnessThe hardness agreed between the manufacturer and the user shall not differ from the nominal value by more than 5 Shore A when tested in accordance with ISO 7619-1 on a special test spe
37、cimen. Alternatively, the hardness can be tested on the plunger stoppers in accordance with ISO 48. If tested according to ISO 48, the microhardness shall not differ by more than 5 IRHD from the type sample.The manufacturer should provide suitable test specimens upon request.7.2.2 Resistance to agei
38、ngThe maximum time between the date of manufacture of the plunger stoppers and their pharmaceutical use should be agreed upon between the manufacturer and the user.The plunger stoppers shall maintain their performance characteristics throughout the entire shelf-life of the medicinal product, which i
39、s tested as part of the stability test by the user.NOTE Ageing depends on storage and handling conditions. A guide to storage of vulcanized rubber is given in ISO 2230.7.3 Chemical requirementsThe aqueous extractables of the plunger stopper material shall not exceed the limits specified for elastome
40、ric parts defined in ISO 8871-1.7.4 Biological requirementsThe requirements in ISO 8871-4 shall apply.8 LabellingPacked plunger stoppers that meet the requirements of this part of ISO 11040 can be labelled with the designation given in Clause 5.DIN ISO 11040-5:2013-12 10 Bibliography1 ISO 48, Rubber
41、, vulcanized or thermoplastic Determination of hardness (hardness between 10 IRHD and 100 IRHD)2 ISO 2230, Rubber products Guidelines for storage3 ISO 3302-2, Rubber Tolerances for products Part 2: Geometrical tolerances4 ISO 8362-5, Injection containers for injectables and accessories Part 5: Freeze drying closures for injection vials5 ISO 9997, Dental cartridge syringes6 ISO 15378, Primary packaging materials for medicinal products Particular requirements for the application of ISO 9001:2008, with reference to Good Manufacturing Practice (GMP)DIN ISO 11040-5:2013-12 11
