1、raising standards worldwideNO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAWBSI Standards PublicationBS ISO 11040-6:2012Prefilled syringesPart 6: Plastic barrels for injectablesBS ISO 11040-6:2012 BRITISH STANDARDNational forewordThis British Standard is the UK implementation of
2、 ISO 11040-6:2012.The UK participation in its preparation was entrusted to TechnicalCommittee CH/212, IVDs.A list of organizations represented on this committee can beobtained on request to its secretary.This publication does not purport to include all the necessaryprovisions of a contract. Users ar
3、e responsible for its correctapplication. The British Standards Institution 2012. Published by BSI StandardsLimited 2012ISBN 978 0 580 69635 0ICS 11.040.25Compliance with a British Standard cannot confer immunity fromlegal obligations.This British Standard was published under the authority of theSta
4、ndards Policy and Strategy Committee on 30 April 2012.Amendments issued since publicationDate Text affectedBS ISO 11040-6:2012 ISO 2012Prefilled syringes Part 6: Plastic barrels for injectablesSeringues prremplies Partie 6: Cylindres en plastique pour produits injectablesINTERNATIONAL STANDARDISO110
5、40-6First edition 2012-04-01Reference number ISO 11040-6:2012(E)BS ISO 11040-6:2012ISO 11040-6:2012(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 m
6、eans, electronic 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 copyrigh
7、tiso.orgWeb www.iso.orgPublished in SwitzerlandBS ISO 11040-6:2012ISO 11040-6:2012(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 thro
8、ugh ISO technical 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 collabor
9、ates closely 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 Standard
10、s. Draft 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
11、 document may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights.ISO 11040-6 was prepared by Technical Committee ISO/TC 76, Transfusion, infusion and injection, and blood processing equipment for medical and pharmaceutical use.ISO 11040 c
12、onsists 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 Part 3: Seals for dental local anaesthetic cartridges Part 4: Glass barrels for injectables Par
13、t 5: Plunger stoppers for injectables Part 6: Plastic barrels for injectablesThe following parts are under preparation: Part 7: Packaging systems for prefillable ready-to-use syringes ISO 2012 All rights reserved iiiBS ISO 11040-6:2012ISO 11040-6:2012(E)IntroductionUntil now, ampoules and injection
14、bottles have been mainly used as primary packaging material for the administration of injectables. However, for the injection of the liquid medicinal products stored in these containers, a hypodermic syringe combined with the appropriate injection cannula is also needed. This requires that the medic
15、inal product be transferred into the hypodermic syringe before its final use. This procedure is not only time-consuming; it can also easily result in mix-ups and possible contamination.In conjunction with the appropriate sealing components, pre-filled single use syringes conforming to this part of I
16、SO 11040 form a safe system for the transport, storage and administration of medicine. Due to relatively simple handling procedures, they permit fast injection of the medicinal products contained within them.This part of ISO 11040 can also be used by engineers as a basis for the development and mark
17、eting of standardized filling and processing equipment, e.g. so-called tub and nest filling presentations. Manufacturers of filling equipment and ancillary processing equipment can use this part of ISO 11040 to achieve a certain degree of unification with regard to the design of these standardized i
18、tems of equipment.NOTE Primary packaging materials are an integral part of medicinal products. Thus, the principles of the current Good Manufacturing Practices (cGMP) apply to the manufacturing of these components (see ISO 15378).iv ISO 2012 All rights reservedBS ISO 11040-6:2012Prefilled syringes P
19、art 6: Plastic barrels for injectables1 ScopeThis part of ISO 11040 specifies the materials, dimensions and requirements for plastic barrels (single-chamber design) for injection preparations, which are to be subsequently filled and assembled on standardized processing equipment.It is applicable to
20、pre-filled plastic syringes intended for single use only.Pre-filled syringes can be produced on dedicated and specifically designed processing equipment. This part of ISO 11040 is not applicable to such dedicated pre-filled syringes.Before the final approval for human use is granted, compatibility t
21、ests applying the intended pharmaceuticals are carried out. This part of ISO 11040 does not specify the procedures for such compatibility tests.2 Normative referencesThe following referenced documents are indispensable for the application of this document. For dated references, only the edition cite
22、d applies. For undated references, the latest edition of the referenced document (including any amendments) applies.ISO 594-1, Conical fittings with a 6 % (Luer) taper for syringes, needles and certain other medical equipment Part 1: General requirements1)ISO 594-2, Conical fittings with 6 % (Luer)
23、taper for syringes, needles and certain other medical equipment Part 2: Lock fittings2)ISO 7886-1:1993, Sterile hypodermic syringes for single use Part 1: Syringes for manual useISO 10993-1, Biological evaluation of medical devices Part 1: Evaluation and testing within a risk management processISO 1
24、1040-5, Prefilled syringes Part 5: Plunger stoppers for injectablesISO 15223-1:3), Medical devices Symbols to be used with medical device labels, labelling and information to be supplied Part 1: General requirementsISO 15378:2011, Primary packaging materials for medicinal products Particular require
25、ments for the application of ISO 9001:2000, with reference to Good Manufacturing Practice (GMP)European Pharmacopoeia 7, available at http:/www.edqm.eu 1) To be replaced by ISO 80369-7, Small-bore connectors for liquids and gases in healthcare applications Part 7: Connectors with 6 % (Luer) taper fo
26、r intravascular or hypodermic applications, which is under preparation.2) To be replaced by ISO 80369-7, Small-bore connectors for liquids and gases in healthcare applications Part 7: Connectors with 6 % (Luer) taper for intravascular or hypodermic applications, which is under preparation.3) To be p
27、ublished.INTERNATIONAL STANDARD ISO 11040-6:2012(E) ISO 2012 All rights reserved 1BS ISO 11040-6:2012ISO 11040-6:2012(E)3 Dimensions and designation3.1 Dimensions of the barrelThe dimensions of the barrel shall be in accordance with Figure 1 and Table 1. These are the minimum required dimensions. De
28、pending on the application, any other dimensions should be agreed between the manufacturer and the customer. Head designs of plastic barrels are shown in Annex A.Table 1 Barrel dimensionsDimensions in millimetresNominal volumeNominal dimension tolerancesml d1d2aL L1h1d3d40,56,8 to 8,2 0,16,8 to 9,4
29、0,1b4,6 to 4,8 0,157,0 to 64,8 0,247,5 to 54,1 0,21,8 to 2,1 0,113,4 to 13,8 0,110,5 to 11,0 0,11c8,1 to 9,4 0,16,3 to 6,5 0,164,0 to 64,5 0,254,0 to 54,5 0,21,9 to 2,3 0,113,7 to 13,8 0,110,5 to 11,0 0,11d10,8 to 11,4 0,18,5 to 8,75 0,145,9 to 46,9 0,235,2 to 35,9 0,21,9 to 2,3 0,117,75 0,1 14,70 0
30、,12,2510,8 to 11,4 0,18,5 to 8,75 0,164,4 to 66,8 0,253,9 to 54,6 0,21,9 to 2,3 0,117,75 0,1 14,70 0,1310,8 to 11,4 0,18,5 to 8,75 0,182,4 to 84,6 0,271,7 to 72,4 0,21,9 to 2,3 0,117,75 0,1 14,70 0,1514,4 to 15,0 0,111,7 to 12,2 0,176,5 to 80,0 0,264,3 to 66,7 0,22,0 to 2,4 0,122,9 to 23,1 0,119,40
31、to 19,9 0,11016,6 to 18,0 0,114,1 to 14,7 0,197,7 to 100,5 0,286,2 to 87,3 0,22,0 to 2,4 0,126,9 to 27,4 0,121,50 to 21,9 0,12021,2 to 22,7 0,1518,9 to 19,1 0,15107,3 to 114,9 0,295,6 to 96,8 0,22,7 to 3,1 0,1532,25 to 38,8 0,1525,15 to 25,9 0,155029,2 to 32,3 0,226,4 to 29,3 0,2128,8 to 151,2e 0,51
32、18,7 to 128,2e 0,52,7 to 3,1 0,245,00 to 50,0 0,233,2 to 39,10 0,210035,2 to 35,5 0,231,8 to 32,2 0,2169,8 0,5 156,4 0,52,7 to 3,1 0,247,65 0,2 41,45 0,2aFor the specification of the inner diameter, the specification of the plunger shall be considered with regard to break loose force and sustaining
33、force. The size of the inner diameter also depends on the plastics material. bThis range is dedicated to barrels with an integrated Luer lock.cLong.dShort or standard.eThis range is required in order to consider particular applications, such as pumps and injectors.NOTE When there are particular dime
34、nsional requirements, which is common when a syringe is used in combination with injectors, it is recommended that these requirements be agreed between the supplier and the customer.2 ISO 2012 All rights reservedBS ISO 11040-6:2012ISO 11040-6:2012(E)Dimensions in millimetresForm A Form B Form CNOTE
35、1 Edges can be slightly rounded.NOTE 2 The design of the finger flange is agreed between the manufacturer and the customer.Figure 1 Typical example of a barrel and plastic finger flange for a pre-filled syringe ISO 2012 All rights reserved 3BS ISO 11040-6:2012ISO 11040-6:2012(E)3.2 Design3.2.1 Head
36、designThe type of head design shall be agreed upon between the provider of the barrel component and the company responsible for filling and finishing the plastic pre-filled syringe. For the Luer and the Luer lock design, ISO 594-1 and ISO 594-2 shall apply. Annex A includes certain examples of head
37、designs.3.2.2 Dead spaceWhen tested in combination with the selected piston in accordance with ISO 11040-5, the dead space in the barrel and the nozzle with the piston fully inserted shall be as given in ISO 7886-1:1993, Table 1.4 Requirements4.1 GeneralThe attention of the provider of the barrel co
38、mponent and the company responsible for filling and finishing the plastic pre-filled syringe is drawn to applicable performance requirements in monographs of, for example, the European Pharmacopoeia (Ph. Eur.), the United States Pharmacopoeia (USP) or the Japanese Pharmacopoeia (JP).4.2 Material4.2.
39、1 GeneralFor the manufacturing of the barrels, suitable polymers shall be selected and used, based upon the intended application and processing techniques, which include, for example, the method of sterilization or the method of decontamination. The material shall exhibit the appropriate performance
40、 properties, e.g. oxygen and water permeability.NOTE For guidance on materials, as well as polymer material codification, see Annex B.4.2.2 Duty of notification concerning modifications to polymersFor change control and notification procedures between the company transforming the polymer into a prim
41、ary packaging material and the pharmaceutical company using it for injectable drug products, requirements given in ISO 15378:2011, 7.3.7 and 7.5.1.2 shall apply.NOTE Particular attention is drawn to change control procedures and notification of changes by suppliers of raw material.4.3 Physical requi
42、rements4.3.1 SterilizationIf the syringes are delivered sterile, they shall be sterilized using a suitable validated sterilization method. Suitable methods are given in ISO 11135-1, ISO 17665-1, ISO 11137 or ISO 14937.4.3.2 Clarity and transparencyThe requirements and test method given in the Ph. Eu
43、r. 7, Section 3.2.8 shall apply.Any possible colouring, for example regarding light shielding, shall be agreed between the user and the manufacturer of the primary packaging material.4 ISO 2012 All rights reservedBS ISO 11040-6:2012ISO 11040-6:2012(E)4.3.3 Particulate contaminationsSyringes shall be
44、 manufactured such that any particulate contamination is avoided.Current pharmacopoeias identify visible particulates as undesirable but do not define the size or put a limit on the allowable number. It is recommended that the supplier and the customer agree upon the size and number of visible parti
45、cles and the test method. NOTE See Ph. Eur. 7, 2.9.19, Particulate contamination: sub-visible particles and 2.9.20, Particulate contamination: visible particles; USP, General Chapter Particulate Matter in Injections16; and JP, 6.06 Foreign Insoluble Matter Test for Injections and 6.07 Insoluble Part
46、iculate Matter Test for Injections17.4.3.4 LubricantsFor silicone oil, attention is drawn to applicable quality and quantity requirements in respective pharmacopoeias. For other lubricants, appropriate in-house monographs shall be applied.If the interior surfaces of the syringe barrel are lubricated
47、, the lubricant shall not be visible, under normal or corrected-to-normal vision, as droplets or particles.4.4 Chemical requirementsThe materials used for manufacturing the syringes shall be chosen such that the risk of them releasing chemical constituents that can migrate into the injectables is mi
48、nimized. NOTE For limit values and test methods, see regional or national pharmacopoeias or the EMA Guideline for chemical constituents of extracts18.For investigation of leachables and extractables of the syringe barrel, all packaging materials thereof in the same head space as the syringe barrel s
49、hall be considered. It shall be ensured that printing inks or adhesive labels used on the plastic syringes do not affect the performance of the syringe and its content.4.5 Biological requirementsThe material shall comply with biological requirements, i.e. toxic, cytotoxic, bacteriostatic, bactericidal, pyrogenic or haemolytic reactions, in accordance with relevant national or regi
