1、 Reference number ISO 15759:2005(E) ISO 2005INTERNATIONAL STANDARD ISO 15759 Second edition 2005-04-01 Medical infusion equipment Plastics caps with inserted elastomeric liner for containers manufactured by the blow fillseal (BFS) process Matriel de perfusion usage mdical Capsules plastiques avec un
2、 joint base dlastomre pour rcipients produits par le procd dextrusion/soufflage/remplissage (ESR) ISO 15759:2005(E) PDF disclaimer This PDF file may contain embedded typefaces. In accordance with Adobes licensing policy, this file may be printed or viewed but shall not be edited unless the typefaces
3、 which are embedded are licensed to and installed on the computer performing the editing. In downloading this file, parties accept therein the responsibility of not infringing Adobes licensing policy. The ISO Central Secretariat accepts no liability in this area. Adobe is a trademark of Adobe System
4、s Incorporated. Details of the software products used to create this PDF file can be found in the General Info relative to the file; the PDF-creation parameters were optimized for printing. Every care has been taken to ensure that the file is suitable for use by ISO member bodies. In the unlikely ev
5、ent that a problem relating to it is found, please inform the Central Secretariat at the address given below. ISO 2005 All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopy
6、ing 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 office Case postale 56 CH-1211 Geneva 20 Tel. + 41 22 749 01 11 Fax + 41 22 749 09 47 E-mail copyrightiso.org Web www.iso.org Published in Switzerl
7、and ii ISO 2005 All rights reservedISO 15759:2005(E) ISO 2005 All rights reserved iiiContents Page Foreword iv Introduction v 1 Scope 1 2 Normative references . 1 3 Dimensions and designation . 2 3.1 Plastics cap for attachment by welding technique (Form A) . 2 3.2 Plastics cap for attachment by col
8、lar technique (Form B) . 3 3.3 Elastomeric liner . 4 4 Materials for cap and liner 4 5 Plastics cap Physical requirements and testing. 5 5.1 Leak-resistance test 5 5.2 Opening force 5 6 Liner Physical requirements and testing.5 6.1 General requirements . 5 6.2 Hardness 5 6.3 Fragmentation (coring).
9、5 6.4 Penetration force. 5 6.5 Dynamic spike-retention capability. 5 6.6 Static spike-retention capability of the liner and leak resistance of the piercing area 5 6.7 Resealability 5 7 Plastics cap Chemical requirements and testing . 5 8 Liner Chemical requirements and testing 6 9 Biological require
10、ments for plastics cap and liner . 6 10 Packaging 6 11 Storage. 6 12 Marking. 6 Annex A (normative) Leak-resistance test. 7 Annex B (normative) Opening force needed to expose the piercing area . 8 Annex C (normative) Fragmentation (coring) 9 Annex D (normative) Penetration force 10 Annex E (normativ
11、e) Dynamic spike retention capability 12 Annex F (normative) Static spike-retention capability of the liner and leak resistance of the piercing area 13 Annex G (normative) Resealability . 14 Annex H (normative) Holding device for elastomeric liner 15 Annex I (normative) Reference spike . 16 Bibliogr
12、aphy . 17 ISO 15759:2005(E) iv ISO 2005 All rights reservedForeword ISO (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 technical committ
13、ees. 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 closely with the Int
14、ernational 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 International
15、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 may be the s
16、ubject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. ISO 15759 was prepared by Technical Committee ISO/TC 76, Transfusion, infusion and injection equipment for medical and pharmaceutical use. This second edition cancels and replaces the first edit
17、ion (ISO 15759:2002), which has been technically revised. ISO 15759:2005(E) ISO 2005 All rights reserved vIntroduction The materials used to manufacture blowfillseal (BFS) containers are primary packaging materials suitable for storing infusion solutions until they are administered. This Internation
18、al Standard deals with plastics caps with inserted elastomeric liners for use with blowfillseal containers and describes their dimensional and functional requirements. This International Standard takes into account that the cap is not a primary packaging component. INTERNATIONAL STANDARD ISO 15759:2
19、005(E) ISO 2005 All rights reserved 1Medical infusion equipment Plastics caps with inserted elastomeric liner for containers manufactured by the blowfill seal (BFS) process 1 Scope This International Standard specifies the dimensional and functional requirements for plastics caps with inserted elast
20、omeric liners, attached to the infusion container (BFS container) by welding or by collar technique. These caps are intended for use in the packaging and handling of liquid drugs for parenteral delivery. 2 Normative references The following referenced documents are indispensable for the application
21、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 48, Rubber, vulcanized or thermoplastic Determination of hardness (hardness between 10 IRHD and 100 IRHD) ISO 2230, Ru
22、bber products Guidelines for storage ISO 2768-1, General tolerances Part 1: Tolerances for linear and angular dimensions without individual tolerance indications ISO 3302-1, Rubber Tolerances for products Part 1: Dimensional tolerances ISO 7500-1, Metallic materials Verification of static uniaxial t
23、esting machines Part 1: Tension/ compression testing machines Verification and calibration of the force-measuring system ISO 7864, Sterile hypodermic needles for single use ISO 8871-1, Elastomeric parts for parenterals and for devices for pharmaceutical use Part 1: Extractables in aqueous autoclavat
24、es ISO 15759:2005(E) 2 ISO 2005 All rights reserved3 Dimensions and designation 3.1 Plastics cap for attachment by welding technique (Form A) General tolerances for Form A plastics caps shall be in accordance with ISO 2768-1; dimensions shall be in accordance with Figure 1. Elastomeric liners for su
25、ch caps shall be in accordance with ISO 3302-1. Plastics cap(s) of Form A in accordance with this International Standard shall be designated as follows: Cap ISO 15759-BFS-A Dimensions in millimetres Key 1 measuring point at the centre aDiameter of score line. Figure 1 Dimensions for Form A plastics
26、caps ISO 15759:2005(E) ISO 2005 All rights reserved 33.2 Plastics cap for attachment by collar technique (Form B) Dimensions for Form B plastics caps shall be in accordance with Figure 2. Plastics cap(s) of Form B in accordance with this International Standard shall be designated as follows: Cap ISO
27、 15759-BFS-B Dimensions in millimetres Key 1 measuring point at the centre a Diameter of score line. Figure 2 Dimensions for Form B plastics caps ISO 15759:2005(E) 4 ISO 2005 All rights reserved3.3 Elastomeric liner Dimensions for elastomeric liners for plastics caps of Form A or Form B shall be in
28、accordance with Figure 3. Elastomeric liners in accordance with this International Standard shall be designated as follows: Elastomeric liner ISO 15759 Figure 3 illustrates a typical liner design. Other liner designs are permitted. Dimensions in millimetres Key 1 trimming edge max. 30,2 aTarget area
29、. Figure 3 Dimensions for elastomeric liners for plastics caps of Form A or Form B 4 Materials for cap and liner 4.1 Materials shall be in accordance with the requirements in Clauses 6, 7, 8 and 9. The choice of plastics and elastomeric materials shall be subject to agreement between manufacturer an
30、d customer. 4.2 Resistance to ageing depends largely on pre-sterilization techniques, storage and handling conditions. The period during which cap and liner shall comply with the requirements of this International Standard is subject to agreement between manufacturer and customer. 4.3 Compatibility
31、of the drug with the liner shall be assessed by the user. 4.4 ISO 2230 describes storage guidelines for vulcanized elastomeric parts. ISO 15759:2005(E) ISO 2005 All rights reserved 55 Plastics cap Physical requirements and testing 5.1 Leak-resistance test When performing the leak-resistance test of
32、the covered piercing area in accordance with Annex A, no leakage shall be observed. 5.2 Opening force When testing the opening force needed to expose the piercing area in accordance with Annex B, the required force shall not exceed 80 N and shall not tear the cap outside the piercing area. 6 Liner P
33、hysical requirements and testing 6.1 General requirements 6.1.1 Injection gates and sprues are not allowed in the sealing area, i.e. between cap and liner. 6.1.2 Marks, indentations and spacers are allowed. The height of spacers shall not exceed 0,3 mm. 6.2 Hardness Hardness requirements shall be ag
34、reed between manufacturer and customer. The hardness shall not differ from the nominal value by more than when 5 IRHD tested in accordance with ISO 48. 6.3 Fragmentation (coring) When testing for fragmentation in accordance with Annex C, no more than seven fragments of diameter equal to or greater t
35、han 50 m shall be observed per ten piercings. 6.4 Penetration force When testing for penetration in accordance with Annex D, the force required to penetrate the liner shall not exceed 80 N. The average value shall not exceed 75 N. 6.5 Dynamic spike-retention capability When tested in accordance with
36、 Annex E, the measured retention force shall not fall below 15 N. 6.6 Static spike-retention capability of the liner and leak resistance of the piercing area When tested in accordance with Annex F, no leakage shall be observed between the spike and liner during a period of 4 h and the spike shall no
37、t fall out. 6.7 Resealability When performing the test in accordance with Annex G, no air shall escape. 7 Plastics cap Chemical requirements and testing The plastics material used to manufacture the cap shall be physiologically harmless. ISO 15759:2005(E) 6 ISO 2005 All rights reserved8 Liner Chemic
38、al requirements and testing The liners shall fulfil the minimum requirements for Type II materials in accordance with ISO 8871-1. 9 Biological requirements for plastics cap and liner Biological requirements are not part of this International Standard; however, since biological tests are required by
39、most of the national Pharmacopoeia or other health authority regulations, they are mandatory for manufacturers and users in countries where such regulations exist. Where none exist, reference should be made to biological tests, e.g. as described in the United States Pharmacopeia or other pharmacopoe
40、ia. 10 Packaging The packaging shall protect the plastics caps and liners during transportation and storage in such a way that their function is not impaired and they remain clean. 11 Storage The plastics caps and liners shall be stored as specified in ISO 2230 and shall not be exposed to UV radiati
41、on. Under these conditions they shall maintain compliant with the requirements of this International Standard throughout a storage period agreed on between manufacturer and customer. 12 Marking The packaging of plastics caps and liners, which comply with the requirements of this International Standa
42、rd, shall be marked as specified in Clause 3, e.g. Cap ISO 15759-BFS-B ISO 15759:2005(E) ISO 2005 All rights reserved 7Annex A (normative) Leak-resistance test A.1 Principle The resistance of the covered piercing area to penetration by surface-active penetrant is determined. A.2 Reagent A.2.1 Surfac
43、e-active penetrant, comprising a mixture of aliphatic hydrocarbons with surface-active substances and colorants. A.3 Preparation Autoclave ten liners at sterilization conditions agreed on between manufacturer and customer (typically 106 C for 50 min or 121 C for 30 min) and cool down to ambient temp
44、erature. A.4 Procedure A.4.1 Carefully remove the liners from the ten caps and cover the piercing area with penetrant. A.4.2 Leave the penetrant on the piercing area for 60 min. A.4.3 Count the number of samples penetrated by the penetrant. A.5 Expression of results Record the number of leak failure
45、s. ISO 15759:2005(E) 8 ISO 2005 All rights reservedAnnex B (normative) Opening force needed to expose the piercing area B.1 Principle The force needed to remove the lid of the plastics cap in order to expose the piercing area is determined. B.2 Apparatus B.2.1 Tensile testing machine, Class 1, in ac
46、cordance with ISO 7500-1, with a suitable holding device. B.3 Preparation Autoclave ten liners at sterilization conditions agreed on between manufacturer and customer (typically 106 C for 50 min or 121 C for 30 min) and cool down to ambient temperature. B.4 Procedure B.4.1 Fix the cap securely on th
47、e tensile testing machine. B.4.2 Remove the lid axially at a speed of 200 mm/min. B.4.3 Record the force, with a tolerance of 2 N. B.4.4 Repeat B.4.1 to B.4.3 with the remaining samples. B.5 Expression of results Calculate the average from ten measurements. Indicate the maximum value. ISO 15759:2005
48、(E) ISO 2005 All rights reserved 9Annex C (normative) Fragmentation (coring) C.1 Principle Liners to be tested are pierced with a spike. Fragments resulting from piercing the liner are collected and counted in order to assess the relative tendency of the liner to fragment. C.2 Apparatus C.2.1 Holdin
49、g device, for liner in accordance with Annex H. Other suitable holding devices may be used provided equivalent results are obtained. C.2.2 Spike, in accordance with Annex I. C.2.3 Membrane filter set. C.3 Preparation C.3.1 Autoclave ten liners at sterilization conditions agreed on between manufacturer and customer (typically 106 C for 50 min or 121 C for 30 min) and cool down to ambient temperature. C.4 Procedure C.4.1 Fill the holding device with distill
