1、BS ISO 11040-8:2016Prefilled syringesPart 8: Requirements and test methods forfinished prefilled syringesBSI Standards PublicationWB11885_BSI_StandardCovs_2013_AW.indd 1 15/05/2013 15:06BS ISO 11040-8:2016 BRITISH STANDARDNational forewordThis British Standard is the UK implementation of ISO 11040-8
2、:2016.The UK participation in its preparation was entrusted to Technical Committee CH/212, IVDs.A list of organizations represented on this committee can be obtained on request to its secretary.This publication does not purport to include all the necessary provisions of a contract. Users are respons
3、ible for its correct application. The British Standards Institution 2016.Published by BSI Standards Limited 2016ISBN 978 0 580 87310 2 ICS 11.040.25 Compliance with a British Standard cannot confer immunity from legal obligations.This British Standard was published under the authority of the Standar
4、ds Policy and Strategy Committee on 30 November 2016.Amendments/corrigenda issued since publicationDate T e x t a f f e c t e dBS ISO 11040-8:2016 ISO 2016Prefilled syringes Part 8: Requirements and test methods for finished prefilled syringesSeringues prremplies Partie 8: Exigences et mthodes dessa
5、i pour seringues prremplies prtes lemploiINTERNATIONAL STANDARDISO11040-8First edition2016-11-15Reference numberISO 11040-8:2016(E)BS ISO 11040-8:2016ISO 11040-8:2016(E)ii ISO 2016 All rights reservedCOPYRIGHT PROTECTED DOCUMENT ISO 2016, Published in SwitzerlandAll rights reserved. Unless otherwise
6、 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 address below
7、 or ISOs member body in the country of the requester.ISO copyright officeCh. de Blandonnet 8 CP 401CH-1214 Vernier, Geneva, SwitzerlandTel. +41 22 749 01 11Fax +41 22 749 09 47copyrightiso.orgwww.iso.orgBS ISO 11040-8:2016ISO 11040-8:2016(E)Foreword ivIntroduction v1 Scope .12 Normative references 1
8、3 Terms and definitions .24 User requirements24.1 Definition of intended use . 24.2 Risk management . 34.3 Application of usability engineering 35 System characterization .35.1 Critical dimensions 35.2 Description of components and materials 45.2.1 General 45.2.2 Barrel . 45.2.3 Plunger stoppers 55.
9、2.4 Additional components 55.3 Description of the content of the finished prefilled syringe 56 Performance requirements .56.1 General . 56.2 Break loose and extrusion forces 56.3 Burst resistance 66.4 Break resistance . 66.5 Closure system forces and torques 66.6 Connectivity with fluid path connect
10、ors . 66.7 Residual volume . 66.8 Needle penetration force 66.9 Needle pull-out force . 66.10 Sharps injury protection requirements . 66.11 Liquid leakage beyond plunger 76.12 Markings . 77 Pharmaceutical requirements .77.1 General . 77.2 Drug-container interaction 77.3 Biological requirements 77.4
11、Container closure integrity 77.5 Deliverable volume 87.6 Particles (visible and subvisible) 88 Documentation .8Bibliography 9 ISO 2016 All rights reserved iiiContents PageBS ISO 11040-8:2016ISO 11040-8:2016(E)ForewordISO (the International Organization for Standardization) is a worldwide federation
12、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. I
13、nternational 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 those
14、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 (see
15、 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 docume
16、nt 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 ex
17、pressions related to conformity assessment, as well as information about ISOs adherence to the World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see the following URL: www.iso.org/iso/foreword.html.The committee responsible for this document is ISO/TC 76, Transfusion
18、, infusion and injection, and blood processing equipment for medical and pharmaceutical 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 car
19、tridges Part 3: Seals for dental local anaesthetic cartridges Part 4: Glass barrels for injectables and sterilized subassembled syringes ready for filling Part 5: Plunger stoppers for injectables Part 6: Plastic barrels for injectables Part 7: Packaging systems for sterilized subassembled syringes r
20、eady for filling Part 8: Requirements and test methods for finished prefilled syringesiv ISO 2016 All rights reservedBS ISO 11040-8:2016ISO 11040-8:2016(E)IntroductionHistorically, injectable (parenteral) liquid pharmaceutical products have been mainly provided in primary containers (i.e. ampoules a
21、nd vials) which required the liquid to be transferred into a hypodermic syringe and combined with the appropriate injection needle before its final use. This procedure is not only time-consuming, but also presents a great number of possibilities for contamination and use errors.Over the past several
22、 years, the presentation of liquid pharmaceutical products in prefilled syringes for single use, many with staked needles, is becoming more prevalent. The simplicity of use that is provided not only benefits their use in the clinical setting, but also enables these to be used by lay users in a home
23、setting.The standardization of the requirements for prefilled syringes has been addressed by ISO/TC 76 in two ways: the specification of the components of the prefilled syringe prior to filling is included in the previous parts of the ISO 11040 series; the requirements for the final prefilled syring
24、e, presented to the user as a finished product, are addressed in this part of ISO 11040.Finished prefilled syringes require marketing authorization as a drug, in some regions as a combination product or as a medical device, depending on the content and the intended use. The syringe plays a dual role
25、 in the prefilled syringe product as a container closure system and as a delivery device. Safety, performance and usability need to be considered, as well in case of intended preassembly, copackaging or label reference for use with other devices and equipment. This part of ISO 11040 addresses the co
26、ntent and syringe as a system, with the intent to ensure the successful performance for its intended purpose.There are other international and national standards and guidance publications and, in some countries, national regulations that are applicable to medical devices and pharmaceuticals. Their r
27、equirements might supersede or complement this part of ISO 11040. Developers and manufacturers of finished prefilled syringes are encouraged to investigate and determine whether there are any other requirements relevant to the safety or marketability of their products. ISO 2016 All rights reserved v
28、BS ISO 11040-8:2016BS ISO 11040-8:2016Prefilled syringes Part 8: Requirements and test methods for finished prefilled syringes1 ScopeThis part of ISO 11040 is applicable to aseptically filled or terminally sterilized finished prefilled syringes (intended for single use only) based on ISO 11040-4 or
29、ISO 11040-6, together with ISO 11040-5, for parenteral injection preparations with focus on quality, functional performance and safety requirements, as well as relevant test methods.Finished prefilled syringes which have undergone an additional preparation step by the user before injection (e.g. dil
30、uent syringes that have been emptied for reconstitution and in which the reconstituted drug solution has been aspirated after reconstitution) are excluded from the scope of this part of ISO 11040.NOTE 1 This part of ISO 11040 can also be used as a guidance for other types, designs and/or sizes of pr
31、efilled syringes, e.g. dual chamber prefilled syringes.NOTE 2 In case the finished prefilled syringes are used in a needle-based injection system, see also ISO 11608-3.NOTE 3 Attention is drawn to applicable national or regional regulations such as Ph. Eur1), USP2)or JP3).NOTE 4 Finished prefilled s
32、yringes containing so-called borderline products, e.g. hyaluronic acid, are included in the scope of this part of ISO 11040, though they are not always regulated as a pharmaceutical product.2 Normative referencesThe following documents, in whole or in part, are normatively referenced in this documen
33、t 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 11040-4:2015, Prefilled syringes Part 4: Glass barrels for injectables and sterilized subass
34、embled syringes ready for fillingISO 11040-5, Prefilled syringes Part 5: Plunger stoppers for injectablesISO 11040-6, Prefilled syringes Part 6: Plastic barrels for injectablesISO 23908, Sharps injury protection Requirements and test methods Sharps protection features for single-use hypodermic needl
35、es, introducers for catheters and needles used for blood samplingISO 80369-1, Small-bore connectors for liquids and gases in healthcare applications Part 1: General requirementsISO 80369-7, Small-bore connectors for liquids and gases in healthcare applications Part 7: Connectors with 6% (Luer) taper
36、 for intravascular or hypodermic applications1) See http:/www.edqm.eu/.2) See http:/www.usp.org/.3) See http:/www.pmda.go.jp.INTERNATIONAL STANDARD ISO 11040-8:2016(E) ISO 2016 All rights reserved 1BS ISO 11040-8:2016ISO 11040-8:2016(E)ISO 80369-20, Small-bore connectors for liquids and gases in hea
37、lthcare applications Part 20: Common test methodsISO 7886-1:2015, Sterile hypodermic syringes for single use Part 1: Syringes for manual useIEC 62366, Medical devices Application of usability engineering to medical devices3 Terms and definitionsFor the purposes of this document, the following terms
38、and definitions apply.3.1finished prefilled syringeprefilled container closure system for parenteral injection preparations as it is marketed, including e.g. assembly of components, terminal sterilization and final packaging3.2manufacturernatural or legal person holding the licence for the pharmaceu
39、tical product with responsibility for the design, manufacture, packaging, and labelling of a finished prefilled syringe, before it is placed on the market or put into service, regardless of whether these operations are carried out by that person or on that persons behalf by a third party3.3risk mana
40、gementsystematic application of management policies, procedures and practices to the tasks of analysing, evaluating, controlling and monitoring riskSOURCE: ISO 14971:2007, 2.223.4userpatient or health care provider (clinical personnel, doctor, or lay person) who prepares and/or uses the finished pre
41、filled syringe4 User requirements4.1 Definition of intended useThe manufacturer shall define the intended use of the finished prefilled syringe. Aspects to be considered shall include the following: users including their health status; the route of administration; target tissue; additional medical d
42、evices or application aids that are used for application, e.g. needle-based injection systems, infusion tubes, reconstitution aids, sterile hypodermic needles, plunger rod/finger flange; characteristics of the environment during transport, storage and use; interactions between user, environment and
43、prefilled syringe; point of use, e.g. hospital, homecare; frequency of application; criticality of medication, e.g. medication for acute care or for chronic diseases.2 ISO 2016 All rights reservedBS ISO 11040-8:2016ISO 11040-8:2016(E)4.2 Risk managementManufacturers shall follow a risk-based approac
44、h during the design, development, manufacture and life cycle of the finished prefilled syringe like exemplary described by ISO 14971. Risk management shall consider the intended use, interactions between content and container, and environmental conditions. This can result in product-specific require
45、ments and test methods that differ from what is outlined in this part of ISO 11040.If the prefilled syringe is intended to be used in combination with preattached, copackaged or label referenced devices and equipment, the manufacturer shall ensure that the whole combination, including the connection
46、 system, is safe, usable and does not impair the specified performances of the devices.NOTE For filling process, see Reference 17.4.3 Application of usability engineeringThe usability of the prefilled syringe shall be considered and validated according to a process compliant with IEC 62366.NOTE 1 Fo
47、r further information, see Reference 16.NOTE 2 The instructions for use are part of the usability testing.5 System characterization5.1 Critical dimensionsCritical dimensions shall be defined considering the intended use of the finished prefilled syringe. Special focus shall be given to: interfaces w
48、ith other devices (e.g. sharp injury prevention features or needle-based injection systems, needleless connection devices), components and users; connectivity with other devices at the point of use (e.g. IV access systems or needles); plunger stopper position depending on the intended use (e.g. use
49、in needle-based injection systems).Figure 1 includes examples on how to measure the plunger stopper position on finished prefilled syringes. ISO 2016 All rights reserved 3BS ISO 11040-8:2016ISO 11040-8:2016(E)a) Example 1 b) Example 2Key1 plunger stopperl1distance from the plunger stopper to the top of the 90 cone (mechanical or optical gage)l2and l3distance from the plunger stopper to the back end of the syringeFigure 1 Examples for measuring plunger the stopper position for finished prefille
