1、raising standards worldwideNO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAWBSI Standards PublicationPen systemsPart 3: Seals for pen-injectors for medical useBS ISO 13926-3:2012National forewordThis British Standard is the UK implementation of ISO 13926-3:2012.The UK participat
2、ion in its preparation was entrusted to Technical CommitteeCH/212, IVDs.A list of organizations represented on this committee can be obtained onrequest to its secretary.This publication does not purport to include all the necessary provisions of acontract. Users are responsible for its correct appli
3、cation. The British Standards Institution 2013Published by BSI Standards Limited 2013ISBN 978 0 580 71020 9ICS 11.040.25Compliance with a British Standard cannot confer immunity fromlegal obligations.This British Standard was published under the authority of the StandardsPolicy and Strategy Committe
4、e on 31 March 2013.Amendments issued since publicationAmd. No. Date Text affectedBRITISH STANDARDBS ISO 13926-3:2012 ISO 2012Pen systems Part 3: Seals for pen-injectors for medical useSystmes de stylos-injecteurs Partie 3: Joints pour stylos-injecteurs usage mdicalINTERNATIONAL STANDARDISO13926-3Fir
5、st edition2012-05-01Reference numberISO 13926-3:2012(E)BS ISO 13926-3:2012ISO 13926-3:2012(E)ii ISO 2012 All rights reservedCOPYRIGHT PROTECTED DOCUMENT ISO 2012All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means, ele
6、ctronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or ISOs member body in the country of the requester.ISO copyright officeCase postale 56 CH-1211 Geneva 20Tel. + 41 22 749 01 11Fax + 41 22 749 09 47E-mail copyrightiso.orgW
7、eb www.iso.orgPublished in SwitzerlandBS ISO 13926-3:2012ISO 13926-3:2012(E)ForewordISO (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 t
8、echnical committees. Each member body interested in a subject for which a technical 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 clos
9、ely with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.International 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
10、International Standards adopted by the technical committees are circulated to the member bodies for voting. Publication 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
11、 may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights.ISO 13926-3 was prepared by Technical Committee ISO/TC 76, Transfusion, infusion and injection, and blood processing equipment for medical and phamaceutical use.ISO 13926 consists of
12、 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 ISO 2012 All rights reserved iiiBS ISO 13926-3:2012ISO 13926-3:2012(E)Introd
13、uctionPrimary packaging components made of elastomeric materials are an integral part of medicinal products. As such, the principles of current Good Manufacturing Practices (cGMP) are applicable to the manufacturing of these components.Principles of cGMP are described in, for example, ISO 15378 and
14、GMP Guidelines published by the European Community and the United States of America.iv ISO 2012 All rights reservedBS ISO 13926-3:2012Pen systems Part 3: Seals for pen-injectors for medical use1 ScopeThis part of ISO 13926 specifies the shape, dimensions, material, performance requirements and label
15、ling 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 nature and performance of the primary packaging.2 Normative referencesThe following referenced documents are i
16、ndispensable 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 (all parts), Rubber Tolerances for productsISO 7619-1, Rubber, vulcanized or ther
17、moplastic 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 parenterals and for devices for pharmaceutical use Part 1: Extractables in aqueous autoclavatesISO 8871-4, Elast
18、omeric 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 pharmaceutical use Part 5: Functional requirements and testingISO 8872, Aluminium caps for transfusion, infusion
19、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, Pen systems Part 1: Glass cylinders for pen-injectors for medical useISO 13926-2, Pen systems Part 2: Plunger
20、 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 published.INTERNATIONAL STANDARD ISO 13926-3:2012(E) ISO 2012 All rights reserved 1BS ISO 13926-3:2012ISO 13926-3:20
21、12(E)4 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 useTable 1 Dimensions o
22、f 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 to 1,95 9,85 4,0aThe he
23、ight 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 such that a sufficient pre
24、ss-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.2 ISO 2012 All rights reservedBS ISO 13926-3:2012IS
25、O 13926-3:2012(E)5 Designation 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 sea
26、l type A (mono-layer 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 suitab
27、ly lacquered.6.2 DiscDiscs 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 elas
28、tomeric material shall 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
29、Requirements7.1 GeneralThe 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 nomin
30、al value by more than 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 manufactur
31、er should provide suitable 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). ISO 2012 All rights reserved 3BS ISO 13926-3:2012I
32、SO 13926-3:2012(E)Figure 2 Schematic representation of butt-end angle7.2.3 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
33、 and the pharmaceutical use should be agreed upon between the manufacturer 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
34、the storage and handling conditions. A guide to storing vulcanized 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 LabellingPacke
35、d seals which meet the requirements of this part of ISO 13926 can be labelled with the designation given in Clause 5.4 ISO 2012 All rights reservedBS ISO 13926-3:2012ISO 13926-3:2012(E)Annex A (normative) Leakage testA.1 PrincipleWater-filled cartridges are prepared, using the seals to be tested. By
36、 means of a suitable device, a force is applied to the seal during a defined time interval. Any observed leakage 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 accord
37、ance 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 Suitable 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
38、 A.3.2.A.3 ProcedureA.3.1 Take 10 cartridges and fill them, using the seals to be tested, with water that is as 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 hold
39、er (A.2.5), into the pressurizing device (A.2.6), and apply a force, F, as calculated in accordance with Formula (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 1
40、3926-1, the inner diameter of the glass cylinder is designated d2)Check for leakage at the seal.SAFETY PRECAUTIONS 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. ISO 2012 All rights reserved 5BS ISO 13926
41、-3:2012ISO 13926-3:2012(E)A.4 Expression of resultsReport the number of leakages observed at the seal.Report whether the testing of the seals and the plunger stoppers (see ISO 13926-2) has been combined.6 ISO 2012 All rights reservedBS ISO 13926-3:2012ISO 13926-3:2012(E)Bibliography1 ISO 48, Rubber,
42、 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 Manufac
43、turing 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 Regulations ISO 2012 All rights reserved 7BS ISO 13926-3:2012This page deliberately left blankThis page deliberately left blankBSI is the indepe
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