BS ISO 11040-4-2015 Prefilled syringes Glass barrels for injectables and sterilized subassembled syringes ready for filling《预灌装注射器 待灌装可注射和无菌子组装注射器用玻璃筒》.pdf

1、BSI Standards PublicationBS ISO 11040-4:2015Prefilled syringesPart 4: Glass barrels for injectables andsterilized subassembled syringes ready forfillingBS ISO 11040-4:2015 BRITISH STANDARDNational forewordThis British Standard is the UK implementation of ISO 11040-4:2015.It supersedes BS ISO 11040-4

2、:2007 which is withdrawn.The UK participation in its preparation was entrusted to TechnicalCommittee CH/212, IVDs.A list of organizations represented on this committee can beobtained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. U

3、sers are responsible for its correctapplication. The British Standards Institution 2015. Published by BSI StandardsLimited 2015ISBN 978 0 580 81075 6ICS 11.040.25Compliance with a British Standard cannot confer immunity fromlegal obligations.This British Standard was published under the authority of

4、 theStandards Policy and Strategy Committee on 30 April 2015.Amendments issued since publicationDate Text affectedBS ISO 11040-4:2015 ISO 2015Prefilled syringes Part 4: Glass barrels for injectables and sterilized subassembled syringes ready for fillingSeringues prremplies Partie 4: Cylindres en ver

5、re pour produits injectables et seringues pr-assembles strilises prremplissablesINTERNATIONAL STANDARDISO11040-4Third edition2015-04-01Reference numberISO 11040-4:2015(E)BS ISO 11040-4:2015ISO 11040-4:2015(E)ii ISO 2015 All rights reservedCOPYRIGHT PROTECTED DOCUMENT ISO 2015All rights reserved. Unl

6、ess otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the

7、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.orgWeb www.iso.orgPublished in SwitzerlandBS ISO 11040-4:2015ISO 11040-4:2015(E)Foreword ivIntroduction vi1 Scope .12

8、Normative references 13 Terms and definitions .24 General requirements .34.1 Quality systems . 34.2 Testing 34.3 Documentation . 35 Syringe barrel 45.1 Design including dimensions 45.2 Functional testing of Luer connection 75.3 Material . 75.4 Performance requirements 75.4.1 Hydrolytic resistance .

9、75.4.2 Annealing quality 75.4.3 Lubrication of the inner surface . 75.4.4 Flange breakage resistance. 75.4.5 Luer cone breakage resistance 86 Sterilized subassembled syringes ready for filling.86.1 General . 86.2 Sterility 86.3 Pyrogenicity/endotoxins 96.4 Particles . 96.5 Additional requirements to

10、 specific components of sterilized subassembled syringes ready for filling . 96.5.1 Barrel . 96.5.2 Needle 106.5.3 Closure system 116.6 Closure system barrel integrity . 127 Packaging 128 Labelling .12Annex A (informative) Examples of types of sterilized subassembled syringes ready for filling 13Ann

11、ex B (informative) Head designs .15Annex C (normative) Test methods for syringe barrels 17Annex D (informative) Sample preparation for endotoxin and particulate determination 23Annex E (informative) Glide force test method to evaluate syringe lubrication 27Annex F (informative) Needle penetration te

12、st 30Annex G (normative) Test methods for closure systems 33Annex H (informative) Dye solution tightness test48Bibliography .50 ISO 2015 All rights reserved iiiContents PageBS ISO 11040-4:2015ISO 11040-4:2015(E)ForewordISO (the International Organization for Standardization) is a worldwide federatio

13、n of national standards bodies (ISO member bodies). The work of preparing International Standards is normally carried out through 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.

14、 International organizations, governmental and non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.The procedures used to develop this document and thos

15、e intended for its further maintenance are described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the different types of ISO documents should be noted. This document was drafted in accordance with the editorial rules of the ISO/IEC Directives, Part 2 (s

16、ee www.iso.org/directives).Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of any patent rights identified during the development of the docu

17、ment will be in the Introduction and/or on the ISO list of patent declarations received (see www.iso.org/patents).Any trade name used in this document is information given for the convenience of users and does not constitute an endorsement.For an explanation on the meaning of ISO specific terms and

18、expressions related to conformity assessment, as well as information about ISOs adherence to the WTO principles in the Technical Barriers to Trade (TBT) see the following URL: Foreword - Supplementary informationThe committee responsible for this document is ISO/TC 76, Transfusion, infusion and inje

19、ction, and blood processing equipment for medical and pharmaceutical use.This third edition cancels and replaces the second edition (ISO 11040-4:2007), which has been technically revised and contains the following changes: Scope has been extended by adding sterilized subassembled syringes ready for

20、filling and appropriate requirements, as well as test methods, have been included; general requirements have been added on quality systems, testing, and documentation; requirements on labelling have been revised; requirements on packaging have been added; requirements on syringes barrels have been r

21、evised by adding requirements and related test methods for flange breakage resistance and Luer cone breakage resistance, adding requirements on lubrication, adding requirements and guidance on tolerances for Luer conical fittings, as well as on functional testing of Luer connections, and deleting th

22、e clause on designation.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 Part 3: Seals for dental local anaesthetic cartridgesiv ISO

23、2015 All rights reservedBS ISO 11040-4:2015ISO 11040-4:2015(E) Part 4: Glass barrels for injectables and sterilized subassembled syringes ready for filling Part 5: Plunger stoppers for injectables Part 6: Plastics barrels for injectables Part 7: Packaging systems for sterilized subassembled syringes

24、 ready for filling Part 8: Requirements and test methods for finished prefilled syringes ISO 2015 All rights reserved vBS ISO 11040-4:2015ISO 11040-4:2015(E)IntroductionIn the past, ampoules and injection vials were mainly used for (parenteral) injectable products. However, for the injection of the

25、products contained in those ampoules and vials, a hypodermic syringe combined with the appropriate injection needle is also needed. This means the injectable product has to be transferred by the user into the hypodermic syringe before its final use. This procedure is not only time-consuming, but als

26、o presents a great number of possibilities for contamination.To ensure safe use of an injectable product, prefilled syringes for single use are on the market for many years. Without a doubt, such prefilled syringes permit immediate injection of the product contained after relatively simple handling.

27、 These syringes can also be used in injectors with automated functions where further and particular requirements apply.Based on the diameter of the prefilled syringes, appropriate components, such as rubber plungers, tip caps, needle shields, and other closure systems can also be standardized. In co

28、njunction with the right sealing components, they offer a system for (parenteral) injectable use. The producers of filling machines can apply this part of ISO 11040 to achieve a degree of standardization in the equipment of the machines.At the start of prefilled syringe processing by the pharmaceuti

29、cal industry, syringes made of tubing glass were delivered to the pharmaceutical companies in the form of so called non-sterile “bulkware” only. The process steps washing, drying, inner lubrication, sealing the syringe with a closure system, sterilization, as well as filling and closing, were then p

30、erformed in the pharmaceutical companies. Processing of “bulkware” is performed like this until today. Sterilized subassembled syringes have partially replaced non-sterile “bulkware”.In the case of sterilized subassembled syringes ready for filling, responsibility for the aforementioned process step

31、s relevant to the injectable product lies with the manufacturer of the primary packaging material. Following the assembly of the needle shield on syringes with a staked needle or tip caps for the Luer cone version, the subassembled syringes are placed into so called nests. The nests, in turn, are pl

32、aced into a plastic tub. The syringes in the nest are protected by means of an insert liner and the tub itself is sealed by a sealing lid (which is currently and, so far, primarily achieved using a porous material). Thus, the tub properly sealed with the sealing lid represents the “sterile barrier s

33、ystem”. The sealed tub is then wrapped into a sealable bag and, thus, ready for sterilization which is currently and, so far, primarily performed using ethylene oxide.In this form, the sterilized subassembled syringes ready for filling are delivered to the pharmaceutical companies in a sterile condi

34、tion, where they are processed on suitable machines.vi ISO 2015 All rights reservedBS ISO 11040-4:2015Prefilled syringes Part 4: Glass barrels for injectables and sterilized subassembled syringes ready for filling1 ScopeThis part of ISO 11040 applies to tubing-glass barrels (single-chamber design) f

35、or injection preparations, and sterilized subassembled syringes ready for filling.It specifies materials, dimensions, quality, and performance requirements, as well as relevant test methods.This part of ISO 11040 also specifies those components that are part of the sterilized subassembled syringe re

36、ady for filling.Glass barrels and sterilized subassembled syringes ready for filling in accordance with this part of ISO 11040 are intended for single use only.Components to complete the subassembled syringe, such as plunger and rod, are not specified in this part of ISO 11040.NOTE Attention is draw

37、n to applicable national or regional regulations such as Ph. Eur., USP, or JP. Where relevant, specific references to Ph. Eur., USP, and JP have been given in specific clauses or subclauses of this part of ISO 11040.2 Normative referencesThe following documents, in whole or in part, are normatively

38、referenced in this document and are indispensable for its application. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies.ISO 594-1,1)Conical fittings with a 6 % (Luer) taper for syringes, nee

39、dles and certain other medical equipment Part 1: General requirementsISO 594-2,1)Conical fittings with 6 % (Luer) taper for syringes, needles and certain other medical equipment Part 2: Lock fittingsISO 720:1985, Glass Hydrolytic resistance of glass grains at 121 degrees C Method of test and classif

40、icationISO 4802-1, Glassware Hydrolytic resistance of the interior surfaces of glass containers Part 1: Determination by titration method and classificationISO 4802-2, Glassware Hydrolytic resistance of the interior surfaces of glass containers Part 2: Determination by flame spectrometry and classif

41、icationISO 7864, Sterile hypodermic needles for single useISO 7886-1:1993, Sterile hypodermic syringes for single use Part 1: Syringes for manual use1) ISO 594-1 and ISO 594-2 will be replaced by ISO 80369-7 (currently in preparation by ISO/TC 210).INTERNATIONAL STANDARD ISO 11040-4:2015(E) ISO 2015

42、 All rights reserved 1BS ISO 11040-4:2015ISO 11040-4:2015(E)ISO 8871-1, Elastomeric parts for parenterals and for devices for pharmaceutical use Part 1: Extractables in aqueous autoclavatesISO 9626, Stainless steel needle tubing for the manufacture of medical devicesISO 10993-7, Biological evaluatio

43、n of medical devices Part 7: Ethylene oxide sterilization residualsISO 11040-5, Prefilled syringes Part 5: Plunger stoppers for injectablesISO 80369-1, Small-bore connectors for liquids and gases in healthcare applications Part 1: General requirements3 Terms and definitionsFor the purposes of this d

44、ocument, the following terms and definitions apply.3.1customerbusiness entity which purchases syringe barrels or sterilized subassembled syringes ready for filling and conducts further processing or filling as appropriate3.2manufacturerbusiness entity which performs or is otherwise responsible for t

45、he manufacturing of the syringe barrels (bulkware) or for the sterilized subassembled syringes ready for filling by the customer3.3needle shieldsyringe closure used with staked needle subassembled syringes that is designed to protect the needle point/bevel from damage, to allow sterilization of the

46、needle, and to maintain sterility of the contents of the syringe and of the needle up to the time of injection3.4prefilled syringecontainer system filled with the injectable product ready for injectionNote 1 to entry: Components of syringes are barrel, needle, closure system, plunger, and rod. Examp

47、les of sterilized subassembled syringes ready for filling including components are illustrated in Annex A.3.5syringe barrelcylindrical glass body with front end and finger flangeNote 1 to entry: See Figure 1.Note 2 to entry: The syringe barrel can be equipped with a staked needle.3.6sterilized subas

48、sembled syringe ready for fillingsubassembly that has been pre-treated, consisting of a syringe barrel and a closure systemNote 1 to entry: The subassembly has been pre-treated by applying the following processes, as applicable: assembling/lubricating a needle; final washing/pyrogen reduction; dryin

49、g; applying lubricant to the inner surface; sealing the syringe with a closure system;2 ISO 2015 All rights reservedBS ISO 11040-4:2015ISO 11040-4:2015(E) packing (see ISO 11040-7); sterilization.Note 2 to entry: Examples of sterilized subassembled syringes ready for filling including components are illustrated in Annex A.3.7syringe closure systemcomponent or multi-component system designed to close the syringe system at the front end that is designed to allow sterilization of the glass tip and mainta