1、October 2012 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).ICS
2、 11.040.25!$wy“1918486www.din.deDDIN ISO 11040-2Prefilled syringes Part 2: Plunger stoppers for dental local anaesthetic cartridges(ISO 11040-2:2011),English translation of DIN ISO 11040-2:2012-10Vorgefllte Spritzen Teil 2: Kolbenstopfen fr Dentalkarpulen zur Lokalansthesie (ISO 11040-2:2011),Englis
3、che bersetzung von DIN ISO 11040-2:2012-10Seringues prremplies Partie 2: Bouchons-pistons pour cartouches dentaires danesthsie locale(ISO 11040-2:2011),Traduction anglaise de DIN ISO 11040-2:2012-10SupersedesDIN ISO 11040-2:1995-09www.beuth.deDocument comprises pagesIn case of doubt, the German-lang
4、uage original shall be considered authoritative.1109.12 A comma is used as the decimal marker. Contents Page National foreword .3 National Annex NA (informative) Bibliography 4 Introduction .5 1 Scope 6 2 Normative references 6 3 Classification6 4 Shape and dimensions 7 5 Designation 8 6 Material .8
5、 7 Requirements .8 7.1 General 8 7.2 Physical requirements 8 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 . 10 Bibliography . 11 2 DIN ISO 11040-2:2012-10
6、 National foreword This standard 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 Me
7、dizin (Medical Standards Committee), 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 identif
8、ying any or all such patent rights. 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 8871-1 DIN EN ISO 8871-1 ISO 8871-4 DIN EN ISO 8871-4 ISO 9997 DIN EN ISO 9997 ISO 11040-1 DIN ISO 11040-1 I
9、SO 11040-3 DIN ISO 11040-3 ISO 11499 DIN EN ISO 11499 ISO 15378 DIN EN ISO 15378 DIN ISO 11040 consists of the following parts, under the general title Prefilled syringes: Part 1: Glass cylinders for dental local anaesthetic cartridges Part 2: Plunger stoppers for dental local anaesthetic cartridges
10、 Part 3: Seals for dental local anaesthetic cartridges Part 4: Glass barrels for injectables Part 5: Plunger stoppers for injectables Amendments This standard differs from DIN ISO 11040-2:1995-09 as follows: a) the standard has been brought in line with the ISO 8871 standards series; b) the requirem
11、ents for plunger stoppers are now dealt with in this part of DIN ISO 11040 and the requirements for seals are completely covered by ISO 11040-3; c) Table 1 on dimensions of plunger stoppers has been revised; d) the requirements for material, hardness, freedom from leakage and sliding characteristics
12、 have been revised; e) requirements for the resistance to ageing have been added; f) the standard has been editorially revised. 3 DIN ISO 11040-2:2012-10 Previous editions DIN 58358-2: 1986-07 DIN 58367-1: 1975-08, 1984-04, 1986-04 DIN ISO 11040-2: 1995-09 National Annex NA (informative) Bibliograph
13、y 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 methods DIN EN ISO 9997, Den
14、tal cartridge syringes DIN EN ISO 11499, Dentistry Single-use cartridges for local anaesthetics 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 48, Rubber, v
15、ulcanized 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 11040-1, Prefilled syringes Glass cylinders for dental local anaesthetic cartridges DIN ISO 11040-3, Prefilled syringes A
16、luminium caps for dental local anaesthetic cartridges 4 DIN ISO 11040-2:2012-10 Introduction Primary 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 manufacturi
17、ng of these components. Principles of cGMP are described in ISO 15378, and in GMP Guidelines published by the European Community5and the United States of America6. Prefilled syringes Part 2: Plunger stoppers for dental local anaesthetic cartridges 5 DIN ISO 11040-2:2012-10 1 Scope This part of ISO 1
18、1040 specifies the shape, dimensions, material, performance requirements and labelling of plunger stoppers for dental local anaesthetic cartridges intended for single use only. NOTE The potency, purity, stability and safety of a medicinal product during its manufacture and storage can be affected si
19、gnificantly by the nature and performance of the primary packaging. 2 Normative references The 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 doc
20、ument (including any amendments) applies. ISO 48, Rubber, vulcanized or thermoplastic Determination of hardness (hardness between 10 IRHD and 100 IRHD) alternative normative reference to ISO 7619-1 ISO 3302 (all parts), Rubber Tolerances for products ISO 7619-1, Rubber, vulcanized or thermoplastic D
21、etermination of indentation hardness Part 1: Durometer method (Shore hardness) alternative normative reference to ISO 48 ISO 8871-1, Elastomeric parts for parenterals and for devices for pharmaceutical use Part 1: Extractables in aqueous autoclavates ISO 8871-4, Elastomeric parts for parenterals and
22、 for devices for pharmaceutical use Part 4: Biological requirements and test methods ISO 11040-1, Prefilled syringes Part 1: Glass cylinders for dental local anaesthetic cartridges ISO 11040-3, Prefilled syringes Part 3: Seals for dental local anaesthetic cartridges 3 Classification Plunger stoppers
23、 shall be classified as follows: Type A: plunger stoppers without cavities; Type B: plunger stoppers with one cavity; Type C: plunger stoppers with two cavities. 6 DIN ISO 11040-2:2012-10 4 Shape and dimensions 4.1 Shape and dimensions of plunger stoppers shall be as shown in Figure 1 and as given i
24、n Table 1. a) Type A b) Type B c) Type C Key d1, d2diameters of plunger stoppers Figure 1 Shape and dimensions of plunger stoppers showing positions of cavities Table 1 Dimensions of plunger stoppers Dimensions in millimetres DiameterNominal inner diameter of the glass cylinderaTypebd1min. d2max. 6,
25、85 0,15 A 7,1 6,65 6,85 0,15 B 7,2 6,65 6,85 0,15 C 7,4 6,65 a In accordance with ISO 11040-1. b See Clause 3. 4.2 In order to avoid adhesion of the plunger stoppers 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 be
26、tween manufacturer and cartridge assembler. 4.3 If not otherwise specified, general dimensional tolerances shall be in accordance with ISO 3302. 7 DIN ISO 11040-2:2012-10 5 Designation Plunger stoppers can be designated according to their type; see Clause 3 and Figure 1. The designation shall be exp
27、ressed as the word “plunger”, followed by a reference to this part of ISO 11040, followed by the letter designating the type. EXAMPLE Designation of a plunger stopper of Type C (i.e. with two cavities): Plunger ISO 11040-2 C 6 Material The elastomeric material used shall meet the requirements specif
28、ied in Clause 7. Plunger stoppers shall be made from the elastomeric formulation originally tested and approved by the end-user. The manufacturer of plunger stoppers shall ensure the conformance of each delivery with the type sample and compliance with previously agreed functional and compendial req
29、uirements. The elastomeric 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 sh
30、all be evaluated. 7 Requirements 7.1 General The requirements specified in 7.2 to 7.4 represent minimum requirements which refer to the condition of the elastomeric plunger stoppers on receipt by the user. 7.2 Physical requirements 7.2.1 Hardness The hardness agreed between manufacturer and user sha
31、ll not differ from the nominal 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 plunger stoppers in accordance with ISO 48. If tested in accordance with ISO 48, the microhardness shall not differ by mo
32、re than 5 IRHD from the type sample. The manufacturer should provide suitable test specimens upon request. 7.2.2 Freedom from leakage The cartridges shall be free from leakage at the plunger when tested in accordance with the method given in Annex A. 7.2.3 Sliding characteristics The sliding charact
33、eristics are influenced by all components of the container closure systems and process parameters, e.g. siliconization. The testing of complete systems is described in ISO 11499. The results depend on the configuration and the pretreatment (dry, kind of liquid, storage time, etc.). 8 DIN ISO 11040-2
34、:2012-10 7.2.4 Resistance to ageing The maximum time between the date of manufacture and the pharmaceutical use should be agreed upon between the manufacturer of the plunger stoppers and the user. The plunger stoppers shall maintain their performance characteristics throughout the entire shelf life
35、of the medicinal product. The shelf life is determined by the stability test conducted by the user. NOTE Ageing depends upon the storage and handling conditions. A guide to storage of vulcanized rubber is given in ISO 2230. 7.3 Chemical requirements The requirements in ISO 8871-1 apply. 7.4 Biologic
36、al requirements The requirements in ISO 8871-4 apply. 8 Labelling Packed plunger stoppers which meet the requirements of this part of ISO 11040 can be labelled with the designation given in Clause 5. 9 DIN ISO 11040-2:2012-10 Annex A (normative) Leakage test A.1 Principle Water-filled cartridges are
37、 prepared using the plunger stoppers to be tested. By means of a suitable device, force is applied to the plunger stopper during a defined time interval. Any observed leakage is recorded. The leakage test of the plunger stoppers and the seals (see ISO 11040-3) can be combined. A.2 Apparatus A.2.1 Ca
38、rtridge cylinders, in accordance with ISO 11040-1. A.2.2 Plunger stoppers, to be tested. A.2.3 Seals, in accordance with ISO 11040-3. A.2.4 Suitable equipment, to prepare water-filled cartridges. A.2.5 Cartridge holder, for example as specified in ISO 9997 or ISO 11499. A.2.6 Pressurizing device, ca
39、pable of applying a force of (30 3) N. A.3 Procedure A.3.1 Fill 10 cartridges completely with water, ensuring that they are free of any air, using the plunger stoppers to be tested. The water may be replaced by a coloured solution in order to improve the visibility of the leakage. A.3.2 Place the fi
40、rst cartridge, mounted in the cartridge holder (A.2.5), into the pressurizing device (A.2.6), and apply a force of (30 1) N for 1 min. Check for leakage at the plunger stopper. SAFETY PRECAUTIONS Ensure that adequate safety measures are in place to protect the operator. A.3.3 Repeat the operation de
41、scribed in A.3.2 on the remaining cartridges. A.4 Expression of results Report the number of leakages observed at the plunger stopper. Report whether the testing of the plunger stoppers and the seals (see ISO 11040-3) has been combined. 10 DIN ISO 11040-2:2012-10 Bibliography 1 ISO 2230, Rubber prod
42、ucts Guidelines for storage 2 ISO 9997, Dental cartridge syringes 3 ISO 11499, Dentistry Single-use cartridges for local anaesthetics 4 ISO 15378, Primary packaging materials for medicinal products Particular requirements for the application of ISO 9001:2008, with reference to Good Manufacturing Practice (GMP) 5 EC Guide to Good Manufacturing Practice for Medicinal Products, III/2244/87, Rev. 3 January 1998 as amended 6 US/FDA Code of Federal Regulations 11 DIN ISO 11040-2:2012-10
