1、May 2014Translation 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).ICS 11.0
2、40.25!%1i“2147025www.din.deDDIN ISO 13926-3Pen systems Part 3: Seals for pen-injectors for medical use (ISO 13926-3:2012),English translation of DIN ISO 13926-3:2014-05Pen-Systeme Teil 3: Dichtungen fr Pen-Injektoren zur medizinischen Verwendung (ISO 13926-3:2012),Englische bersetzung von DIN ISO 13
3、926-3:2014-05Systmes de stylos-injecteurs Partie 3: Joints pour stylos-injecteurs usage mdical (ISO 13926-3:2012),Traduction anglaise de DIN ISO 13926-3:2014-05www.beuth.deIn case of doubt, the German-language original shall be considered authoritative.Document comprises 12 pages04.14 A comma is use
4、d as the decimal marker. Contents Page National foreword .3 National Annex NA (informative) Bibliography4 Introduction .5 1 Scope .6 2 Normative references .6 3 Classification 6 4 Shape and dimensions 7 5 Designation .8 6 Material 8 6.1 Cap .8 6.2 Disc 8 7 Requirements 8 7.1 General 8 7.2 Physical r
5、equirements .9 7.3 Chemical requirements 9 7.4 Biological requirements .9 8 Labelling 9 Annex A (normative) Leakage test 10 A.1 Principle 10 A.2 Apparatus . 10 A.3 Procedure . 10 A.4 Expression of results . 11 Bibliography . 12 DIN ISO 13926-3:2014-052National foreword This document (ISO 13926-3:201
6、2) has been prepared by Technical Committee ISO/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 Commi
7、ttee), Working Committee NA 063-02-15 AA Elastomere 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 ri
8、ghts. DIN ISO 13926 consists of the following parts, under the general title Pen systems: Part 1: Glass cylinders for pen-injectors for medical use Part 2: Plunger stoppers for pen-injectors for medical use Part 3: Seals for pen-injectors for medical use The DIN Standards corresponding to the Intern
9、ational Standards referred to in this document are as follows: ISO 48 DIN ISO 48 ISO 3302 (all parts) DIN ISO 3302-1 ISO 7619-1 DIN ISO 7619-1 ISO 7885:2010 DIN EN ISO 7885:2010-06 ISO 8871-1 DIN EN ISO 8871-1 ISO 8871-4 DIN EN ISO 8871-4 ISO 8871-5:2005 DIN ISO 8871-5:2006-01 ISO 8872 DIN EN ISO 88
10、72 ISO 11608-3 DIN EN ISO 11608-3 ISO 13926-1 DIN ISO 13926-1 ISO 13926-2 DIN ISO 13926-2 ISO 15378 DIN EN ISO 15378 DIN ISO 13926-3:2014-053National Annex NA (informative) Bibliography DIN EN ISO 7885:2010-06, Dentistry Sterile injection needles for single use DIN EN ISO 8871-1, Elastomeric parts f
11、or 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 methods DIN EN ISO 8872, Aluminium caps for transfusion, infusion an
12、d injection bottles General requirements and test methods DIN EN ISO 11608-3, Needle-based injection systems for medical use Requirements and test methods Part 3: Finished containers DIN EN ISO 15378, Primary packaging materials for medicinal products Particular requirements for the application of I
13、SO 9001:2008, with reference to Good Manufacturing Practice (GMP) DIN ISO 48, Rubber, vulcanized or thermoplastic Determination of hardness (hardness between 10 IRHD and 100 IRHD) DIN ISO 3302-1, Rubber Tolerances for products Part 1: Dimensional tolerances DIN ISO 7619-1, Rubber, vulcanized or ther
14、moplastic Determination of indentation hardness Part 1: Durometer method (Shore hardness) DIN ISO 8871-5:2006-01, Elastomeric parts for parenterals and for devices for pharmaceutical use Part 5: Functional requirements and testing DIN ISO 13926-1, Pen systems Part 1: Glass cylinders for pen-injector
15、s for medical use DIN ISO 13926-2, Pen systems Part 2: Plunger stoppers for pen-injectors for medical use DIN ISO 13926-3:2014-054IntroductionPrimary packaging components made of elastomeric materials are an integral part of medicinal products. As such, the principles of current Good Manufacturing P
16、ractices (cGMP) are applicable to the manufacturing of these components.Principles of cGMP are described in, for example, ISO 15378 and GMP Guidelines published by the European Community and the United States of America.Pen systems Part 3: Seals for pen-injectors for medical useDIN ISO 13926-3:2014-
17、0551 ScopeThis part of ISO 13926 specifies the shape, dimensions, material, performance requirements and labelling of seals for pen-injectors for medical use.NOTE The potency, purity, stability and safety of a medicinal product during its manufacture and storage can be significantly affected by the
18、nature and performance of the primary packaging.2 Normative referencesThe 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 (including any
19、amendments) applies.ISO 3302 (all parts), Rubber Tolerances for productsISO 7619-1, Rubber, vulcanized or thermoplastic Determination of indentation hardness Part 1: Durometer method (Shore hardness)ISO 7885:2010, Dentistry Sterile injection needles for single useISO 8871-1, Elastomeric parts for pa
20、renterals and for devices for pharmaceutical use Part 1: Extractables in aqueous autoclavatesISO 8871-4, Elastomeric parts for parenterals and for devices for pharmaceutical use Part 4: Biological requirements and test methodsISO 8871-5:2005, Elastomeric parts for parenterals and for devices for pha
21、rmaceutical use Part 5: Functional requirements and testingISO 8872, Aluminium caps for transfusion, infusion and injection bottles General requirements and test methodsISO 11608-3, Needle-based injection systems for medical use Requirements and test methods Part 3: Finished containers1)ISO 13926-1,
22、 Pen systems Part 1: Glass cylinders for pen-injectors for medical useISO 13926-2, Pen systems Part 2: Plunger stoppers for pen-injectors for medical use 3 ClassificationSeals shall be classified as follows: type A: seals with a mono-layer disc; type B: seals with a double-layer disc.1) To be publis
23、hed.DIN ISO 13926-3:2014-0564 Shape and dimensions4.1 The shapes and dimensions of seals shall be as shown in Figure 1 and as given in Table 1.Dimensions in millimetresa) Seal with a mono-layer disc b) Seal with a double-layer discFigure 1 Shape and dimensions of seals for pen-injectors for medical
24、useTable 1 Dimensions of sealsDimensions in millimetresNominal size Type Total cap heightaThickness of discInner cap diameterBore diameterh1h2d1d20,15 0,15 0,05 0,27,5 A 4,85 to 4,9 1,3 to 1,5 7,5 3,07,5 B 4,85 to 5,3 1,45 to 1,95 7,5 3,010,0 A 4,85 to 4,9 1,3 to 1,5 9,85 4,010,0 B 4,85 to 5,3 1,45
25、to 1,95 9,85 4,0aThe height of the seal depends on the thickness and hardness of the disc.4.2 For type B seals, both single layers shall be continuous. The ratio of thickness of the single layers shall be agreed upon between the supplier and the user.4.3 The diameter of the rubber discs shall be suc
26、h that a sufficient press-fit in the aluminium cap is achieved and that the discs cannot fall out.4.4 If not otherwise specified, general dimensional tolerances shall be in accordance with ISO 3302.4.5 The surface of the discs can be structured in order to avoid sticking.DIN ISO 13926-3:2014-0575 De
27、signation Seals can be designated according to their type (see Clause 3 and Figure 1). The designation shall be expressed as the word “Seal”, followed by a reference to this part of ISO 13926, followed by the nominal size, followed by the type letter.EXAMPLE Designation of a seal type A (mono-layer
28、disc) for a nominal head size of the cartridge of 7,5 mm complying with the requirements in this part of ISO 13926:Seal ISO 13926-3 7,5 A6 Material6.1 CapGeneral requirements for aluminium caps shall be in accordance with ISO 8872.In addition, the cap shall be anodized or suitably lacquered.6.2 Disc
29、Discs shall be made from the elastomeric formulation originally tested and approved by the end user. The manufacturer of the discs shall ensure conformance of each delivery with the type sample and compliance with previously agreed functional and compendial requirements.The elastomeric material shal
30、l withstand two sterilization cycles when autoclaving in saturated steam at (121 2) C for 30 min without impairment of its function under the conditions of normal use. In case of other sterilization methods, e.g. irradiation, the suitability of the material shall be evaluated.7 Requirements7.1 Gener
31、alThe requirements specified in 7.2 to 7.4 represent minimum requirements which refer to the condition of the seals on receipt by the user.7.2 Physical requirements7.2.1 Hardness of the discThe hardness agreed between the manufacturer and the user shall not differ from the nominal value by more than
32、 5 Shore A when tested in accordance with ISO 7619-1 on a special test specimen. Alternatively, the hardness can be tested on the discs according to ISO 48. If tested according to ISO 48, the micro-hardness shall not differ by more than 5 IRHD from the type sample.The manufacturer should provide sui
33、table test specimens upon requests.7.2.2 FragmentationThe requirements and test method specified in ISO 8871-5:2005, 4.2, shall apply, using a needle with an outer diameter of 0,4 mm, conforming to ISO 7885:2010, 5.3 (butt end).DIN ISO 13926-3:2014-058Figure 2 Schematic representation of butt-end an
34、gle7.2.3 Freedom from leakageThe cartridge shall be free from leakage at the seal when tested in accordance with Annex A.7.2.4 ResealabilityISO 11608-3 applies.7.2.5 Resistance to ageingThe maximum time between the date of manufacture and the pharmaceutical use should be agreed upon between the manu
35、facturer of the seals and the user.The seals shall maintain their performance characteristics throughout the entire shelf-life of the medicinal product, which is tested as part of the stability test by the user.NOTE Ageing depends on the storage and handling conditions. A guide to storing vulcanized
36、 rubber is given in ISO 2230.7.3 Chemical requirementsThe requirements in ISO 8871-1 shall apply for the disc.7.4 Biological requirementsThe requirements in ISO 8871-4 shall apply.Toxicity tests apply to the disc only.8 LabellingPacked seals which meet the requirements of this part of ISO 13926 can
37、be labelled with the designation given in Clause 5.DIN ISO 13926-3:2014-059Annex A (normative) Leakage testA.1 PrincipleWater-filled cartridges are prepared, using the seals to be tested. By means of a suitable device, a force is applied to the seal during a defined time interval. Any observed leaka
38、ge is recorded.The leakage test of the seals and the plunger stoppers (see ISO 13926-2) can be combined.A.2 ApparatusA.2.1 Cartridge cylinders with a silicone-treated inner surface in accordance with ISO 13926-1.A.2.2 Seals to be tested.A.2.3 Plunger stoppers in accordance with ISO 13926-2.A.2.4 Sui
39、table equipment to prepare water-filled cartridges.A.2.5 Cartridge holder, for example, as described in ISO 11608-3.A.2.6 Device, capable of applying a force as calculated in accordance with A.3.2.A.3 ProcedureA.3.1 Take 10 cartridges and fill them, using the seals to be tested, with water that is a
40、s air-free as possible. NOTE The water can be replaced by a coloured solution in order to improve the visibility of the leakage.A.3.2 Place the first cartridge, mounted in the cartridge holder (A.2.5), into the pressurizing device (A.2.6), and apply a force, F, as calculated in accordance with Formu
41、la (A.1) for 1 min.F = 0,64 N/mm2 d2(A.1)whereF is the force to be applied, in newtons;d is the inner diameter of the glass cylinder, in millimetres, in accordance with ISO 13926-1 (in ISO 13926-1, the inner diameter of the glass cylinder is designated d2)Check for leakage at the seal.SAFETY PRECAUT
42、IONS Adequate safety measures should be in place to protect the operator.A.3.3 Repeat the operation described in A.3.2 on the remaining cartridges.DIN ISO 13926-3:2014-0510A.4 Expression of resultsReport the number of leakages observed at the seal.Report whether the testing of the seals and the plun
43、ger stoppers (see ISO 13926-2) has been combined.DIN ISO 13926-3:2014-0511Bibliography1 ISO 48, Rubber, vulcanized or thermoplastic Determination of hardness (hardness between 10 IRHD and 100 IRHD)2 ISO 2230, Rubber products Guidelines for storage3 ISO 15378, Primary packaging materials for medicinal products Particular requirements for the application of ISO 9001:2008, with reference to Good Manufacturing Practice (GMP)4 EC Guide to Good Manufacturing Practice for Medicinal Products, III/2244/87, Rev. 3 January 1998, as amended5 US/FDA Code of Federal RegulationsDIN ISO 13926-3:2014-0512
