1、BSI Standards PublicationBS ISO 11040-7:2015Prefilled syringesPart 7: Packaging systems for sterilizedsubassembled syringes ready for fillingBS ISO 11040-7:2015 BRITISH STANDARDNational forewordThis British Standard is the UK implementation of ISO 11040-7:2015.The UK participation in its preparation
2、 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 are responsible for its correctapplication. The British Sta
3、ndards Institution 2015. Published by BSI StandardsLimited 2015ISBN 978 0 580 76968 9ICS 11.040.25Compliance with a British Standard cannot confer immunity fromlegal obligations.This British Standard was published under the authority of theStandards Policy and Strategy Committee on 30 April 2015.Ame
4、ndments issued since publicationDate Text affectedBS ISO 11040-7:2015 ISO 2015Prefilled syringes Part 7: Packaging systems for sterilized subassembled syringes ready for fillingSeringues prremplies Partie 7: Systmes demballage pour les seringues strilises prtes lemploi prremplissablesINTERNATIONAL S
5、TANDARDISO11040-7First edition2015-04-01Reference numberISO 11040-7:2015(E)BS ISO 11040-7:2015ISO 11040-7:2015(E)ii ISO 2015 All rights reservedCOPYRIGHT PROTECTED DOCUMENT ISO 2015All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in
6、 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 address below or ISOs member body in the country of the requester.ISO copyright officeCase post
7、ale 56 CH-1211 Geneva 20Tel. + 41 22 749 01 11Fax + 41 22 749 09 47E-mail copyrightiso.orgWeb www.iso.orgPublished in SwitzerlandBS ISO 11040-7:2015ISO 11040-7:2015(E)Foreword ivIntroduction v1 Scope .12 Normative references 13 Terms and definitions .14 Requirements for the packaging system .24.1 Ge
8、neral . 24.2 Nest . 34.3 Tub . 44.4 Insert liner 44.5 Sealing lid 44.6 Protective bag 55 Information to be provided by the manufacturer 56 Marking of the tub .57 Packaging of tubs in trading units/bundles .6Annex A (informative) Design of nests .7Annex B (informative) Determination of nest deflectio
9、n.14Annex C (informative) Design of tubs .17Annex D (informative) Schematic illustrations of examples for the orientation of tubs within the protective bag 19Annex E (informative) Design and dimensions of the protective bag .21Annex F (informative) Test method to determine the distance between the e
10、dge of the protective bag to the rear end of the tub 24Bibliography .27 ISO 2015 All rights reserved iiiContents PageBS ISO 11040-7:2015ISO 11040-7:2015(E)ForewordISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO member bodies). The
11、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. International organizations, governmental and non-gover
12、nmental, 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 those intended for its further maintenance are described in
13、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 (see www.iso.org/directives).Attention is drawn to the pos
14、sibility 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 document will be in the Introduction and/or on the ISO list
15、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 expressions related to conformity assessment, as well as
16、 information about ISOs adherence to the WTO principles in the Technical Barriers to Trade (TBT) see the following URL: Foreword - Supplementary information.The committee responsible for this document is ISO/TC 76, Transfusion, infusion and injection, and blood processing equipment for medical and p
17、harmaceutical use.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 cartridges Part 4: Glas
18、s 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 ready for fillingThe following part is under preparation: Part 8: Requirem
19、ents and test methods for finished prefilled syringesiv ISO 2015 All rights reservedBS ISO 11040-7:2015ISO 11040-7:2015(E)IntroductionAt the start of prefilled syringe processing by the pharmaceutical industry, syringes made of tubing glass were delivered to the pharmaceutical companies in the form
20、of a so called non-sterile “bulkware” only. The process steps like washing, drying, inner lubrication, sealing the syringe with a closure system, sterilization, as well as filling, and closing were then performed in the pharmaceutical companies. Processing of “bulkware” is still performed like this
21、nowadays. Sterilized subassembled syringes have partially replaced the non-sterile “bulkware”.In the case of sterilized subassembled syringes ready for filling, responsibility for the aforementioned process steps relevant to the injectable product lies within the manufacturer of the primary packagin
22、g 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 placed into a plastic tub. The syringes in the nest are protected by means of an insert l
23、iner 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 system”. The sealed tub is then wrapped into a sealable bag and, thus, ready for sterili
24、zation 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 condition where they are processed on suitable machines.The packaging design and material ha
25、ve to ensure sterility and should be compatible with the process of the customer. The packaging characteristics, material, thickness, shape, and resistance to deformations among others are such that they maintain, up to the point of use, the integrity of the product and a validated barrier against p
26、articulate and bacterial contamination. The packaging materials have to fulfil regional and national regulatory requirements. ISO 2015 All rights reserved vBS ISO 11040-7:2015BS ISO 11040-7:2015Prefilled syringes Part 7: Packaging systems for sterilized subassembled syringes ready for filling1 Scope
27、This part of ISO 11040 specifies the packaging system that is used to deliver sterilized subassembled syringes ready for filling in tubs and nests.Downstream processes (processes after filling such as in house/outside transport, reprocessing) can result in specific requirements on the packaging syst
28、em used to deliver sterilized subassembled syringes ready for filling. However, these requirements are not within the scope of this part of ISO 11040.NOTE 1 Glass barrels and sterilized subassembled syringes ready for filling, plungers, and plastic barrels for injectables are specified in ISO 11040-
29、4, ISO 11040-5, and ISO 11040-6.NOTE 2 ISO 11607-2 addresses validation requirements of sealing and packaging processes for medical devices.2 Normative referencesThe following documents, in whole or in part, are normatively referenced in this document and are indispensable for its application. For d
30、ated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies.ISO 11607-1, Packaging for terminally sterilized medical devices Part 1: Requirements for materials, sterile barrier systems and packaging systems
31、3 Terms and definitionsFor the purposes of this document, 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 appropriate3.2insert linerfoil to cover t
32、he filled nest3.3manufacturerbusiness entity which performs or is otherwise responsible for the manufacturing of the syringe barrels (bulkware) or for the sterilized subassembled syringes ready for filling by the customer3.4nestplastic plate with a defined hole pattern for the suspension of the syri
33、nge bodiesINTERNATIONAL STANDARD ISO 11040-7:2015(E) ISO 2015 All rights reserved 1BS ISO 11040-7:2015ISO 11040-7:2015(E)3.5primary packaging materialpackaging materials used in pharmaceutical packaging which will contain, seal, or be used for dose application of a medicinal product and which will h
34、ave direct contact with the medicinal productSOURCE: ISO 15378:2011, definition 3.35.13.6protective bagplastic bag or sealing around the tub3.7sealing lidmicrobial barrier material for sealing the tub3.8packaging systemcombination of the sterile barrier system and protective packagingSOURCE: ISO/TS
35、11139:2006, definition 2.283.9protective packagingconfiguration of materials designed to prevent damage to the sterile barrier system and its contents from the time of their assembly until the point of useSOURCE: ISO/TS 11139:2006, definition 2.37 modified by adding “from the time of their assembly”
36、.3.10sterile barrier systemminimum package that prevents ingress of microorganisms and allows aseptic presentation of product at the point of useNote 1 to entry: For packaging systems for sterilized subassembled syringes ready for filling, the sterile barrier system is formed by the tub and sealing
37、lid.SOURCE: ISO/TS 11139:2006, definition 2.44 modified by adding Note 1 to entry.3.11tubplastic container to accommodate the filled nest4 Requirements for the packaging system4.1 General4.1.1 The introduction of sterilized packaged subassembled syringes into an aseptic filling environment poses a r
38、isk of microbiological and/or particulate contamination of the drug product. The packaging system shall have acceptable microbiological and particulate levels to support the introduction of the sterilized subassembled syringes into an aseptic filling environment. Requirements should be agreed upon b
39、y the manufacturer and the customer.4.1.2 The materials, the sterile barrier system, and the packaging system that enable sterilization and maintain sterility until the point of aseptic filling shall comply with the requirements of ISO 11607-1. The sterile barrier system shall ensure product sterili
40、ty over its shelf-life (i.e. the time sterility is ensured by the integrity of the sterile barrier system in recommended storage conditions). As a minimum, the protective bag protects the tub from external contaminants like dust or dirt. Ideally, it also maintains product sterility over its shelf-li
41、fe and allows for bioburden control at the time of use.2 ISO 2015 All rights reservedBS ISO 11040-7:2015ISO 11040-7:2015(E)4.1.3 Tubs, nests, and protective bags shall allow general processing and aseptic presentation of the sterilized subassembled syringes over their shelf-life. The process steps t
42、o be considered include, but are not limited to the following:a) for tubs including sealing lid and insert liner:1) lid sealing and lid opening;2) conveying;3) nest insertion and extraction;4) stacking and destacking;5) sterilization (e.g. ethylene oxide, gamma) and decontamination (e g. electron be
43、am).b) for nests:1) barrel insertion and extraction;2) filling;3) stoppering;4) stacking and destacking.c) for protective bag:1) sealing;2) folding;3) decontamination;4) cutting and opening.NOTE The process steps described include those at the premises of the manufacturer and of the customer.4.2 Nes
44、tNOTE This subclause covers nests used for sterilized subassembled syringes ready for filling. Nested formats can also be used for plunger stoppers/pistons.4.2.1 For the nest, the following information shall be provided (information on dimensions including tolerances): external dimensions; deflectio
45、n; holes for the syringes; centering openings/lifting openings; defined free space where the lifting tool can engage.Customer and manufacturer should agree upon the dimensions and tolerances of the finished product as delivered.NOTE For information on dimensions, see Annex A. This annex has the inte
46、nt to harmonize products coming to the market to facilitate the handling and processing of the prefilled syringes. ISO 2015 All rights reserved 3BS ISO 11040-7:2015ISO 11040-7:2015(E)4.2.2 The design of the nest shall facilitate the insertion and removal of the sterilized subassembled syringes ready
47、 for filling (e.g. Luer lock adapter (LLA)-syringes) by adding bevels or other means.NOTE For information on design, see Annex A.4.2.3 The maximum acceptable nest deflection should be agreed upon by the manufacturer and customer. The nest deflection can be determined using the test method as describ
48、ed in Annex B.4.3 Tub4.3.1 For tubs, the following information shall be provided (information on dimensions including tolerances): external dimensions including reinforcements/beads, radii, and indentations; dimensions of the reinforcement/bead below the sealing edge, as well the slope of the latera
49、l surfaces.NOTE For information on dimensions, see Annex C. This annex has the intent to harmonize products coming to the market to facilitate the handling and processing of the prefilled syringes.4.3.2 The tub shall allow the sealing of the lid.The tub flange shall be free of sharp edges to protect the integrity of various packaging layers.NOTE For information on design, see Annex C.4.3.3 If sterilization indicators are applied to the tubs, they shall comply with the appropriate International Standards (see ISO 11138 and IS
