SIST EN ISO 11608-3:2022
(Main)Needle-based injection systems for medical use - Requirements and test methods - Part 3: Containers and integrated fluid paths (ISO 11608-3:2022)
Needle-based injection systems for medical use - Requirements and test methods - Part 3: Containers and integrated fluid paths (ISO 11608-3:2022)
This document specifies requirements and test methods for design verification of containers and
integrated fluid paths used with Needle-Based Injection Systems (NISs) according to ISO 11608-1.
It is applicable to single and multi-dose containers either filled by the manufacturer (primary container
closure) or by the end-user (reservoir) (e.g. cartridges, syringes) and fluid paths that are integrated
with the NIS at the point of manufacture.
This document is also applicable to prefilled syringes (see ISO 11040-8) when used with a NIS (see also
scope of ISO 11608-1:2022).
This document is not applicable to the following products:
— sterile hypodermic needles;
— sterile hypodermic syringes;
— sterile single-use syringes, with or without needle, for insulin;
— containers that can be refilled multiple times;
— containers intended for dental use;
— catheters or infusion sets that are attached or assembled separately by the user
Kanülenbasierte Injektionssysteme zur medizinischen Verwendung - Anforderungen und Prüfverfahren - Teil 3: NIS-Behälter und integrierte Flüssigkeitspfade (ISO 11608-3:2022)
Dieses Dokument legt Anforderungen und Prüfverfahren für die Designverifizierung von Behältern und integrierten Flüssigkeitsbahnen fest, die mit kanülenbasierten Injektionssystemen (NISs, en: needle-based injection systems) nach ISO 11608 1 verwendet werden.
Es ist anwendbar auf Einzeldosis- und Mehrfachdosisbehälter, die entweder vom Hersteller (Primärbehälter) oder vom Endanwender befüllt (Vorratsbehälter) (z. B. Karpulen, Spritzen) werden, sowie für Flüssigkeitsbahnen, die am Ort der Herstellung in das NIS integriert werden.
Dieses Dokument ist auch anzuwenden für vorgefüllte Spritzen (siehe ISO 11040 8), wenn sie zusammen mit einem NIS verwendet werden (siehe auch den Anwendungsbereich von ISO 11608 1:2022).
Dieses Dokument ist für folgende Produkte nicht anzuwenden:
— sterile Subkutankanülen;
— sterile Injektionsspritzen;
— sterile Spritzen zum Einmalgebrauch, mit oder ohne Kanüle, für Insulin;
— Behälter, die mehrere Male befüllt werden können;
— zum zahnärztlichen Gebrauch vorgesehene Behälter;
— Katheter oder Infusionssets, die vom Benutzer angebracht oder separat zusammengesetzt werden.
Systèmes d'injection à aiguille pour usage médical - Exigences et méthodes d'essai - Partie 3: Conteneurs et chemins de fluide intégrés (ISO 11608-3:2022)
Le présent document spécifie les exigences et les méthodes d'essai pour vérification de la conception des conteneurs et des chemins de fluide intégrés utilisés avec les systèmes d'injection à aiguille (NIS) conformément à l'ISO 11608-1.
Il est applicable aux conteneurs à dose unique et multidoses, soit remplis par le fabricant (conditionnement primaire) soit par l'utilisateur final (réservoir) (par exemple, cartouches, seringues) et aux chemins de fluide intégrés au NIS au stade de fabrication.
Le présent document est également applicable aux seringues préremplies (voir l'ISO 11040-8) lorsqu'elles sont utilisées avec un NIS (voir également le domaine d'application de l'ISO 11608-1:2022).
Le présent document ne s'applique pas aux produits suivants:
— aux aiguilles hypodermiques stériles;
— aux seringues hypodermiques stériles;
— aux seringues à insuline, stériles, non réutilisables, avec ou sans aiguille;
— aux conteneurs pouvant être remplis plusieurs fois;
— aux conteneurs à usage dentaire;
— aux cathéters ou appareils de perfusion attachés ou assemblés séparément par l'utilisateur.
Peresa za injiciranje za uporabo v medicini - Zahteve in preskusne metode - 3. del: Vsebniki in integrirane fluidne poti (ISO 11608-3:2022)
Ta dokument določa zahteve in preskusne metode za overjanje zasnove vsebnikov in integriranih poti tekočine, ki se uporabljajo skupaj s peresi za injiciranje (NIS) v skladu s standardom ISO 11608-1. Uporablja se za vsebnike za enega ali več odmerkov, ki jih napolni proizvajalec (primarni sistem zapiranja vsebnika) ali končni uporabnik (rezervoar) (npr. ampule, brizge), ter za poti tekočine, integrirane v peresa za injiciranje v času njihove proizvodnje. Ta dokument se uporablja tudi za predhodno napolnjene brizge (glej standard ISO 11040-8), kadar se te uporabljajo skupaj s peresom za injiciranje (glej tudi področje uporabe standarda ISO 11608-1:2022). Ta dokument se ne uporablja za naslednje izdelke: – sterilne podkožne igle; – sterilne podkožne injekcijske brizge; – sterilne injekcijske brizge za inzulin za enkratno uporabo, z iglo ali brez nje; – vsebniki, ki jih je mogoče napolniti večkrat; – vsebniki za zobozdravstveno uporabo; – katetri in infuzijski seti, ki jih uporabnik pritrdi ali sestavi posebej.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 11608-3:2022
01-julij-2022
Nadomešča:
SIST EN ISO 11608-3:2013
Peresa za injiciranje za uporabo v medicini - Zahteve in preskusne metode - 3. del:
Vsebniki in integrirane fluidne poti (ISO 11608-3:2022)
Needle-based injection systems for medical use - Requirements and test methods - Part
3: Containers and integrated fluid paths (ISO 11608-3:2022)
Kanülenbasierte Injektionssysteme zur medizinischen Verwendung - Anforderungen und
Prüfverfahren - Teil 3: NIS-Behälter und integrierte Flüssigkeitspfade (ISO 11608-
3:2022)
Systèmes d'injection à aiguille pour usage médical - Exigences et méthodes d'essai -
Partie 3: Conteneurs et chemins de fluide intégrés (ISO 11608-3:2022)
Ta slovenski standard je istoveten z: EN ISO 11608-3:2022
ICS:
11.040.25 Injekcijske brizge, igle in Syringes, needles an
katetri catheters
SIST EN ISO 11608-3:2022 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 11608-3:2022
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SIST EN ISO 11608-3:2022
EN ISO 11608-3
EUROPEAN STANDARD
NORME EUROPÉENNE
May 2022
EUROPÄISCHE NORM
ICS 11.040.25 Supersedes EN ISO 11608-3:2012
English Version
Needle-based injection systems for medical use -
Requirements and test methods - Part 3: Containers and
integrated fluid paths (ISO 11608-3:2022)
Systèmes d'injection à aiguille pour usage médical - Kanülenbasierte Injektionssysteme zur medizinischen
Exigences et méthodes d'essai - Partie 3: Conteneurs et Verwendung - Anforderungen und Prüfverfahren - Teil
chemins de fluide intégrés (ISO 11608-3:2022) 3: NIS-Behälter und integrierte Flüssigkeitspfade (ISO
11608-3:2022)
This European Standard was approved by CEN on 2 January 2022.
CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this
European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references
concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN
member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by
translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management
Centre has the same status as the official versions.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,
Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2022 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 11608-3:2022 E
worldwide for CEN national Members.
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SIST EN ISO 11608-3:2022
EN ISO 11608-3:2022 (E)
Contents Page
European foreword . 3
2
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SIST EN ISO 11608-3:2022
EN ISO 11608-3:2022 (E)
European foreword
This document (EN ISO 11608-3:2022) has been prepared by Technical Committee ISO/TC 84 "Devices
for administration of medicinal products and catheters" in collaboration with Technical Committee
CEN/TC 205 “Non-active medical devices” the secretariat of which is held by DIN.
This European Standard shall be given the status of a national standard, either by publication of an
identical text or by endorsement, at the latest by November 2022, and conflicting national standards
shall be withdrawn at the latest by November 2022.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 11608-3:2012.
Any feedback and questions on this document should be directed to the users’ national standards
body/national committee. A complete listing of these bodies can be found on the CEN website.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,
Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the
United Kingdom.
Endorsement notice
The text of ISO 11608-3:2022 has been approved by CEN as EN ISO 11608-3:2022 without any
modification.
3
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SIST EN ISO 11608-3:2022
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SIST EN ISO 11608-3:2022
INTERNATIONAL ISO
STANDARD 11608-3
Third edition
2022-04
Needle-based injection systems for
medical use — Requirements and test
methods —
Part 3:
Containers and integrated fluid paths
Systèmes d'injection à aiguille pour usage médical — Exigences et
méthodes d'essai —
Partie 3: Conteneurs et chemins de fluide intégrés
Reference number
ISO 11608-3:2022(E)
© ISO 2022
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SIST EN ISO 11608-3:2022
ISO 11608-3:2022(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2022
All rights reserved. Unless otherwise specified, or required in the context of its implementation, 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
or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
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SIST EN ISO 11608-3:2022
ISO 11608-3:2022(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Requirements . 3
4.1 General . 3
4.2 Container integrity . 4
4.2.1 Container Closure Integrity (CCI) . 4
4.2.2 Resealability — All multi-dose cartridges or reservoirs with discs . 4
4.2.3 Fragmentation (disc coring) – cartridges or reservoirs with discs. 4
4.3 Cannula requirements (as part of the fluid path) . 5
4.3.1 Rigid needles . 5
4.3.2 Soft cannulas . 5
4.4 Fluid line connections . 5
4.5 Medicinal product compatibility . 5
4.5.1 General . 5
4.5.2 Medicinal product compatibility with reservoir and integrated fluid path
materials . 6
4.5.3 Reservoir and integrated fluid path particulate matter . 6
4.5.4 Reservoir and fluid path pyrogenicity . 6
4.5.5 Reservoir and integrated fluid path leachables. 7
4.5.6 Sterilization of the reservoir and/or integrated fluid path . 7
4.6 Medicinal product leakage . 8
5 Test methods . 8
5.1 Resealability for multi-dose cartridges or reservoirs . 8
5.2 Fragmentation (disc coring) – cartridges or reservoirs . 9
5.3 Sub-visible particulates . 10
5.4 Visible particulates . 10
6 Information supplied with the container .10
6.1 General . 10
6.2 Marking on the unit packaging . 10
Annex A (informative) Medicinal product compatibility references – Requirements,
guidance, standards or compendia material .11
Annex B (informative) Historical references to previous editions .14
Annex C (informative) Theoretical support for resealability requirements .17
Annex D (informative) Reservoir and integrated fluid path leachables .20
Annex E (informative) Medicinal product compatibility .22
Annex F (informative) Primary container closure as compared to reservoir and fluid path .24
Bibliography .27
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SIST EN ISO 11608-3:2022
ISO 11608-3:2022(E)
Foreword
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 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 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 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 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 document 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 of the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to
the World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT), see
www.iso.org/iso/foreword.html.
This document was prepared by Technical Committee ISO/TC 84, Devices for administration of medicinal
products and catheters, in collaboration with the European Committee for Standardization (CEN)
Technical Committee CEN/TC 205, Non-active medical devices, in accordance with the Agreement on
technical cooperation between ISO and CEN (Vienna Agreement).
This third edition cancels and replaces the second edition (ISO 11608-3:2012), which has been
technically revised.
The main changes are as follows:
— test methods and dimensions specific to traditional pen-injector “Type A” cartridges have been
removed.
A list of all parts in the ISO 11608 series can be found on the ISO website.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www.iso.org/members.html.
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SIST EN ISO 11608-3:2022
ISO 11608-3:2022(E)
Introduction
Developers and manufacturers of NIS are encouraged to investigate and determine if there are any
other requirements relevant to the safety of their products.
Previous editions of this document focused on multi-dose pen-injector cartridges, important
dimensions (e.g. inner diameter) and related attributes (e.g., disc seal eccentricity, meniscus) deemed
critical for pen-injector form, fit, and function. The previous edition (i.e. ISO 11608-3:2012) included
a more general discussion of "other containers" like syringes given their role in single dose NIS with
automated functions (commonly referred to as auto-injectors).
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SIST EN ISO 11608-3:2022
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SIST EN ISO 11608-3:2022
INTERNATIONAL STANDARD ISO 11608-3:2022(E)
Needle-based injection systems for medical use —
Requirements and test methods —
Part 3:
Containers and integrated fluid paths
1 Scope
This document specifies requirements and test methods for design verification of containers and
integrated fluid paths used with Needle-Based Injection Systems (NISs) according to ISO 11608-1.
It is applicable to single and multi-dose containers either filled by the manufacturer (primary container
closure) or by the end-user (reservoir) (e.g. cartridges, syringes) and fluid paths that are integrated
with the NIS at the point of manufacture.
This document is also applicable to prefilled syringes (see ISO 11040-8) when used with a NIS (see also
scope of ISO 11608-1:2022).
This document is not applicable to the following products:
— sterile hypodermic needles;
— sterile hypodermic syringes;
— sterile single-use syringes, with or without needle, for insulin;
— containers that can be refilled multiple times;
— containers intended for dental use;
— catheters or infusion sets that are attached or assembled separately by the user.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements 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 7864:2016, Sterile hypodermic needles for single use — Requirements and test methods
ISO 8872, Aluminium caps for transfusion, infusion and injection bottles — General requirements and test
methods
ISO 9626:2016, Stainless steel needle tubing for the manufacture of medical devices — Requirements and
test methods
ISO 10555-1:2013, Intravascular catheters — Sterile and single-use catheters — Part 1: General
requirements
ISO 10555-5:2013, Intravascular catheters — Sterile and single-use catheters — Part 5: Over-needle
peripheral catheters
ISO 10993-11, Biological evaluation of medical devices — Part 11: Tests for systemic toxicity
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SIST EN ISO 11608-3:2022
ISO 11608-3:2022(E)
ISO 10993-17, Biological evaluation of medical devices — Part 17: Establishment of allowable limits for
leachable substances
ISO 11040-4, Prefilled syringes — Part 4: Glass barrels for injectables and sterilized subassembled syringes
ready for filling
ISO 11040-5, Prefilled syringes — Part 5: Plunger stoppers for injectables
ISO 11040-6, Prefilled syringes — Part 6: Plastic barrels for injectables and sterilized subassembled
syringes ready for filling
ISO 11040-8, Prefilled syringes — Part 8: Requirements and test methods for finished prefilled syringes
ISO 11607-1, Packaging for terminally sterilized medical devices — Part 1: Requirements for materials,
sterile barrier systems and packaging systems
ISO 11608-1:2022, Needle-based injection systems for medical use — Requirements and test methods —
Part 1: Needle-based injection systems
ISO 13926-1, Pen systems — Part 1: Glass cylinders for pen-injectors for medical use
ISO 13926-2, Pen systems — Part 2: Plunger stoppers for pen-injectors for medical use
ISO 13926-3, Pen systems — Part 3: Seals for pen-injectors for medical use
ISO 21881, Sterile packaged ready for filling glass cartridges
ISO 80369-7, Small-bore connectors for liquids and gases in healthcare applications — Part 7: Connectors
for intravascular or hypodermic applications
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 11608-1 and the following
apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1
cartridge
container for the medicinal product that is closed on one end with a cartridge cap (3.2) and disc (3.5),
and on the other end with a plunger stopper (3.8)
3.2
cartridge cap
component that attaches the disc (3.5) to the cartridge (3.1)
3.3
container closure integrity
CCI
adequacy of primary container closure to maintain a sterile barrier (3.10) against potential contaminants
until the labelled expiration date or first intentional user interaction
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SIST EN ISO 11608-3:2022
ISO 11608-3:2022(E)
3.4
fragmentation
formation of elastomeric particles that are generated when the disc (3.5) or other elastomeric
components that forms part of the primary container closure is pierced by a needle, spike or other
access device for filling or delivery
Note 1 to entry: Disc coring is one mechanism to generate fragments.
3.5
disc
septum
elastomeric closure
component of a container [typically a cartridge (3.1)], which seals the end of the container through
which the medicinal product is accessed
3.6
integrated fluid path
needle-based injection system pathway (NIS), integrated into the NIS at the time of manufacture, that
the medicinal product follows from the container or reservoir to the targeted delivery site
3.7
medicinal product compatibility
evaluation of the medicinal product quality based on combined use with the needle-based injection
system
Note 1 to entry: Impact of medicinal product on device is covered in ISO 11608-1.
3.8
plunger stopper
component that seals one end of the container and moves within the container to cause or accommodate
movement of the medicinal product
3.9
sterility assurance level
SAL
probability of a single viable microorganism occurring after sterilization
Note 1 to entry: It is expressed as the negative exponent to the base 10.
[SOURCE: ISO 11139:2018, 3.275 — modified, "on an item" has been deleted.]
3.10
sterile barrier
system of components that provide a barrier to microbial ingress
4 Requirements
4.1 General
These requirements apply to containers or integrated fluid paths intended to be used with a NIS. When
test methods and specifications are noted, they are included to assist manufacturers and suppliers in
supporting conformity with design specification of the NIS.
Annex F provides illustrated examples of Primary Container Closures (PCC), reservoirs and fluid path
configurations for manufacturer filled and user filled NIS.
Specific requirements for NIS primary container closure system components are:
a) glass syringes (including integrated needles) shall conform with applicable requirements of
ISO 11040-4 and ISO 11040-8;
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SIST EN ISO 11608-3:2022
ISO 11608-3:2022(E)
b) plastic syringes (including integrated needles) shall conform with applicable requirements of
ISO 11040-6 and ISO 11040-8;
c) prefilled syringes (including integrated needles) shall conform with applicable requirements of
ISO 11040-8;
d) syringe plunger stoppers shall conform with applicable requirements of ISO 11040-5;
e) glass cartridges shall conform with applicable requirements of ISO 13926-1 and ISO 21881;
f) cartridge plunger stoppers shall conform with applicable requirements of ISO 13926-2;
g) cartridge discs shall conform with applicable requirements of ISO 13926-3;
h) cartridge caps shall conform with applicable requirements of ISO 8872;
i) all reservoirs provided empty to the user shall be free of droplets of fluid (lubrication) on the
outside or inside surfaces when inspected in accordance with ISO 11608-1:2022, 11.3.
4.2 Container integrity
4.2.1 Container Closure Integrity (CCI)
Container closure integrity shall be ensured until the expiration date or the first intentional user
interaction that breaks CCI.
If the NIS is manufacturer-assembled with a primary container closure to form a single integral unit,
the manufacturing processes, including assembly, shall be shown to not adversely impact container
closure integrity, in accordance with applicable pharmacopeia.
4.2.2 Resealability — All multi-dose cartridges or reservoirs with discs
For all cartridges or reservoirs with discs intended for multiple penetrations, after having been
penetrated in accordance with the test method specified in 5.1, the penetrated discs of 20 cartridges or
reservoirs shall not leak from the penetration site when the cartridge is pressurized.
The disc of the cartridge or reservoir shall be punctured a minimum of 1,0 times the maximum
number of penetrations expected during its intended use. Risk assessment shall assess the impact of
resealability on the function of the NIS to determine if a greater safety factor is required.
4.2.3 Fragmentation (disc coring) – cartridges or reservoirs with discs
Cartridges or reservoirs that are accessed through an elastomeric disc with a needle, spike or other
access device for delivery shall not exceed six elastomeric disc fragments in the visible range (>150 µm
in diameter) per 100 punctures in accordance with the method described in 5.2, collected from both
coring (ejected from the needle) and fragmentation (collected from the liquid expelled from the
container or reservoir).
For single-dose cartridges, a single penetration on each cartridge or reservoir shall be performed.
For multi-dose cartridges or reservoirs, each disc (barrier) shall be punctured a minimum of 1,0 times
the maximum number of penetrations expected during its intended use.
Risk assessment shall assess the impact of fragments on the function of the NIS to determine if a greater
safety factor, additional mitigations or lowering the limit of allowed fragments shall be required.
NOTE The impact of any fragments on the function of the NIS can be assessed through dose accuracy testing.
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SIST EN ISO 11608-3:2022
ISO 11608-3:2022(E)
4.3 Cannula requirements (as part of the fluid path)
4.3.1 Rigid needles
If the integrated fluid path contains a rigid needle, the strength of union between the needle at its
connection point to the NIS shall not break when subjected to the minimum force given in ISO 7864:2016,
Table 2 when tested according to ISO 7864:2016, Annex B. The directions of force shall be applied as the
needle would encounter during removal from the injection site.
For tapered needles, the minimum force given in ISO 7864:2016, Table 2 shall be determined by the
outer diameter at the hub as indicated in ISO 7864:2016, Figure 1.
The performance of the rigid needle part shall fulfil the requirements in ISO 9626:2016, Clause 5 and
ISO 7864:2016, 4.10.4 (paragraph 1), 4.11, 4.12 and 4.13, or an equivalent and applicable standard for
tubing suited to medical use but fabricated in materials other than stainless steel, to ensure the rigid
needle performs as intended for the specific design.
4.3.2 Soft cannulas
If the integrated fluid path contains a soft cannula and an introducer needle, the strength of union
between the soft cannula and NIS, or the introducer needle and the NIS, shall meet the requirements
of ISO 10555-5:2013, 4.3.3.4 to ensure the soft cannula and/or introducer needle remains affixed to the
NIS throughout its intended use. The testing shall consider and address the forces and vectors that the
introducer needle and cannula would encounter during removal from the injection site.
In addition, the soft cannula shall meet the requirements of ISO 10555-1:2013, 4.6 to ensure the soft
cannula performs as intended for the specific design. Additional physical and functional evaluations to
be considered can include flexural fatigue, compression force, kink resistance, burst testing, etc. Risk
assessment shall be relied upon to determine appropriate evaluations.
In addition, Annex A can also be of assistance.
4.4 Fluid line connections
If the NIS requires a separate external fluid line to connect the functional core of the NIS to a distant
injection site, any connections along that fluid line shall withstand a static tensile force of not less than
15 N for 15 s.
If any connection uses a Luer connection, the connector shall conform with ISO 80369-7.
4.5 Medicinal product compatibility
4.5.1 General
All materials of the NIS in direct contact with the medicinal product shall be compatible with the
medicinal product.
When the NIS
...
SLOVENSKI STANDARD
oSIST prEN ISO 11608-3:2020
01-april-2020
Peresa za injiciranje za uporabo v medicini - Zahteve in preskusne metode - 3. del:
Končna embalaža (ISO/DIS 11608-3:2020)
Needle-based injection systems for medical use - Requirements and test methods - Part
3: NIS containers and integrated fluid paths (ISO/DIS 11608-3:2020)
Kanülenbasierte Injektionssysteme zur medizinischen Verwendung - Anforderungen und
Prüfverfahren - Teil 3: Fertigbehälter (ISO/DIS 11608-3:2020)
Systèmes d'injection à aiguille pour usage médical - Exigences et méthodes d'essai -
Partie 3: Conteneurs NIS et chemins de fluide intégrés (ISO/DIS 11608-3:2020)
Ta slovenski standard je istoveten z: prEN ISO 11608-3
ICS:
11.040.25 Injekcijske brizge, igle in Syringes, needles an
katetri catheters
oSIST prEN ISO 11608-3:2020 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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oSIST prEN ISO 11608-3:2020
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oSIST prEN ISO 11608-3:2020
DRAFT INTERNATIONAL STANDARD
ISO/DIS 11608-3
ISO/TC 84 Secretariat: DS
Voting begins on: Voting terminates on:
2020-02-18 2020-05-12
Needle-based injection systems for medical use —
Requirements and test methods —
Part 3:
NIS containers and integrated fluid paths
ICS: 11.040.25
THIS DOCUMENT IS A DRAFT CIRCULATED
This document is circulated as received from the committee secretariat.
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
IN ADDITION TO THEIR EVALUATION AS
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STANDARDS MAY ON OCCASION HAVE TO
BE CONSIDERED IN THE LIGHT OF THEIR
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WHICH REFERENCE MAY BE MADE IN
Reference number
NATIONAL REGULATIONS.
ISO/DIS 11608-3:2020(E)
RECIPIENTS OF THIS DRAFT ARE INVITED
TO SUBMIT, WITH THEIR COMMENTS,
NOTIFICATION OF ANY RELEVANT PATENT
RIGHTS OF WHICH THEY ARE AWARE AND TO
©
PROVIDE SUPPORTING DOCUMENTATION. ISO 2020
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oSIST prEN ISO 11608-3:2020
ISO/DIS 11608-3:2020(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2020
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
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oSIST prEN ISO 11608-3:2020
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Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Requirements . 3
4.1 General . 3
4.2 Container integrity . 4
4.2.1 Container Closure Integrity (CCI) . 4
4.2.2 Resealability — All multi-dose cartridges or reservoirs with discs . 4
4.2.3 Fragmentation (disc coring) – cartridges or reservoirs with discs. 4
4.3 Cannula requirements (as part of the fluid path) . 4
4.3.1 Rigid needles . 4
4.3.2 Soft cannulas . 5
4.4 Fluid line connections . 5
4.5 Medicinal product compatibility . 5
4.5.1 General. 5
4.5.2 Medicinal product compatibility with reservoir and integrated fluid path
materials . 5
4.5.3 Reservoir and integrated fluid path particulate matter . 5
4.5.4 Reservoir and fluid path pyrogenicity . 6
4.5.5 Reservoir and integrated fluid path leachables . 6
4.5.6 Sterility of the reservoir and/or integrated fluid path . 7
4.6 Medicinal product leakage . 7
5 Test methods . 8
5.1 Resealability for multi-dose cartridges or reservoirs . 8
5.2 Fragmentation (disc coring) – cartridges or reservoirs . 8
5.3 Sub-visible particulates . 9
5.4 Visible particulates . 9
6 Information supplied by the manufacturer . 9
6.1 General . 9
6.2 Marking on the unit packaging . 9
Annex A (informative) Pharmaceutical and medicinal product compatibility references
for medicinal product contacting surfaces – Regulations, guidance, standards or
compendia material .10
Annex B (informative) Historical references to ISO 11608-3:2012, Pen-injector cartridges
dimensions and test methods (Clauses 4 and 5) .14
Annex C (informative) Theoretical support for resealability requirements .17
Annex D (informative) Reservoir and integrated fluid path leachables .20
Annex E (informative) Medicinal product compatibility .22
Annex F (informative) Primary container closure .24
Bibliography .26
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oSIST prEN ISO 11608-3:2020
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Foreword
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 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 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 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 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 document 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 of the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's 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.
This document was prepared by Technical Committee ISO/TC 84, Devices for administration of medicinal
products and catheters.
This third edition cancels and replaces the second edition (ISO 11608-3:2012), which has been
technically revised.
The main changes compared to the previous editions are specified in Annex B.
A list of all parts in the ISO 11608 series can be found on the ISO website.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www .iso .org/ members .html.
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Introduction
This document is applicable to containers (e.g. cartridges, syringes) and their integrated fluid paths
intended for use with Needle-based Injection Systems (NIS) covered by the umbrella standard,
ISO 11608-1. Containers may be provided pre-filled from the manufacturer (i.e. primary container
closure) or empty for filling by the user (i.e. reservoir).
Prior versions focused on multi-dose pen-injector cartridges, important dimensions (e.g. inner
diameter) and related attributes (e.g. disc seal eccentricity, meniscus) deemed critical for pen-injector
form, fit, and function. The prior edition also included a more general discussion of "other containers"
like syringes given their role in single dose NIS with automated functions (commonly referred to as
auto-injectors).
The scope of the latest revision of ISO 11608 (all parts) has been expanded to include on-body delivery
devices (ISO 11608-6), resulting in additional possibilities for future container types. This expansion
of 11608-3 to include evolving NIS technologies requires a broader discussion of containers, integrated
fluid paths, and test methods.
Given the expansion in scope of this document, test methods and dimensions specific to traditional pen-
injector “Type A” cartridges have been removed and, for historical reference, that information has been
preserved in informative Annex B.
There are other international and national standards, guidance materials and, in some countries,
national regulations that are applicable to medical devices and pharmaceuticals; their requirements
might supersede or complement this document. Developers and manufacturers of NIS are encouraged
to investigate and determine if there are any other requirements relevant to the safety of their products.
ISO 11608-1 is the umbrella document of the ISO 11608 series. All other parts, including this document,
are to be used in conjunction with ISO 11608-1.
Guidance on transition periods for implementing the requirements of this document is given in
ISO/TR 19244.
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oSIST prEN ISO 11608-3:2020
DRAFT INTERNATIONAL STANDARD ISO/DIS 11608-3:2020(E)
Needle-based injection systems for medical use —
Requirements and test methods —
Part 3:
NIS containers and integrated fluid paths
1 Scope
This document specifies requirements and test methods for design verification of containers and
integrated fluid paths to be used with Needle-Based Injection Systems (NIS) that fulfil the requirements
of ISO 11608-1 (and other subparts as appropriate). It is applicable to single and multi-dose containers
(either filled by the manufacturer [primary container closure] or by the end-user [reservoir]) and fluid
paths that are integrated with the NIS at the point of manufacture.
NOTE Prefilled syringes (ISO 11040-8) are included in the scope when used with a NIS; see also scope of
ISO 11608-1:20xx.
Products excluded from scope are:
— sterile hypodermic needles for single use;
— sterile hypodermic syringes for single use;
— sterile single-use syringes, with or without needle, for insulin;
— containers that can be refilled multiple times;
— containers intended for dental use;
— catheters or infusion sets that are attached or assembled separately by the user.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements 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 7864:2016, Sterile hypodermic needles for single use — Requirements and test methods
ISO 8872, Aluminium caps for transfusion, infusion and injection bottles — General requirements and
test methods
ISO 9626:2016, Stainless steel needle tubing for the manufacture of medical devices — Requirements and
test methods
1)
ISO 10555-1:2013, Intravascular catheters — Sterile and single-use catheters — Part 1: General
requirements
ISO 10555-5:2013, Intravascular catheters — Sterile and single-use catheters — Part 5: Over-needle
peripheral catheters
ISO 10993-11, Biological evaluation of medical devices — Part 11: Tests for systemic toxicity
1) To be published (revises ISO 10555-1:2013). Stage at time of publication ISO/PWI 10555-1:2019.
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ISO 10993-17, Biological evaluation of medical devices — Part 17: Establishment of allowable limits for
leachable substances
ISO 11040-4, Prefilled syringes — Part 4: Glass barrels for injectables and sterilized subassembled syringes
ready for filling
ISO 11040-5, Prefilled syringes — Part 5: Plunger stoppers for injectables
ISO 11040-6, Prefilled syringes — Part 6: Plastic barrels for injectables and sterilized subassembled
syringes ready for filling
ISO 11040-8, Prefilled syringes — Part 8: Requirements and test methods for finished prefilled syringes
ISO 11607-1, Packaging for terminally sterilized medical devices — Part 1: Requirements for materials,
sterile barrier systems and packaging systems
2)
ISO 11608-1, Needle-based injection systems for medical use — Requirements and test methods — Part 1:
Needle-based injection systems
ISO 13926-1, Pen systems — Part 1: Glass cylinders for pen-injectors for medical use
ISO 13926-2, Pen systems — Part 2: Plunger stoppers for pen-injectors for medical use
ISO 13926-3, Pen systems — Part 3: Seals for pen-injectors for medical use
ISO 21881:2019, Sterile packaged ready for filling glass cartridges
ISO 80369-7, Small-bore connectors for liquids and gases in healthcare applications — Part 7: Connectors
for intravascular or hypodermic applications
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 11608-1 and the following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— IEC Electropedia: available at http:// www .electropedia .org/
— ISO Online browsing platform: available at https:// www .iso .org/ obp
3.1
cartridge
container for the medicinal product which is closed on one end with a cartridge cap (3.2) and disc (3.5),
and on the other end with a plunger stopper (3.8)
3.2
cartridge cap
component which attaches the disc (3.5) to the cartridge (3.1)
3.3
container closure integrity
CCI
adequacy of Primary Container Closure (PCC) to maintain a sterile barrier against potential
contaminants until first intentional user interaction
Note 1 to entry: See definition for PCC in ISO 11608-1:20##.
2) To be published (revises ISO 11608-1:2012). Stage at time of publication: ISO/DIS 11608-1:2020.
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3.4
fragmentation
formation of elastomeric particles which are generated when the disc is pierced by a needle, spike or
other access device for filling or delivery
Note 1 to entry: Disc coring is one mechanism to generate fragments
[SOURCE: ISO 8871-5:2016, 3.2 - modified]
3.5
disc
component of a container (typically a cartridge (3.1)), which seals the end of the container through
which the medicinal product is accessed
Note 1 to entry: E.g. disc septum or elastomeric closure.
3.6
fluid path
pathway the medicinal product follows from the container or reservoir to the targeted delivery site
3.7
medicinal product compatibility
impact of the device on the quality of the medicinal product
Note 1 to entry: Impact of medicinal product on device is covered in ISO 11608-1.
3.8
plunger stopper
component that seals one end of the container and interfaces with the delivery device
3.9
sterility assurance level
SAL
probability of a single viable microorganism occurring after sterilization
Note 1 to entry: It is expressed as the negative exponent to the base 10.
[SOURCE: ISO 11139:2018, 3.275 - modified]
3.10
sterile barrier system
system of components that provide a barrier to microbial ingress
4 Requirements
4.1 General
These requirements apply to containers or integrated fluid paths intended to be used with a NIS. When
test methods and specifications are noted, they are included to assist manufacturers and suppliers in
supporting compliance with design specification of the NIS in accordance with the applicable parts of
ISO 11608.
Specific requirements for NIS primary container closure system components are:
a) glass syringes (including integrated needles) shall comply with applicable clauses of ISO 11040-4
and ISO 11040-8;
b) plastic syringes (including integrated needles) shall comply with applicable clauses of ISO 11040-6
and ISO 11040-8;
c) syringe plunger stoppers shall comply with applicable clauses of ISO 11040-5;
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d) glass cartridges shall comply with applicable clauses of ISO 13926-1 and ISO 21881;
e) cartridge plunger stoppers shall comply with applicable clauses of ISO 13926-2;
f) cartridge discs shall comply with applicable clauses of ISO 13926-3;
g) cartridge caps shall comply with applicable clauses of ISO 8872;
h) all reservoirs provided empty to the user shall be free of droplets of fluid (lubrication) on the
outside or inside surfaces when viewed under normal or corrected-to-normal vision.
4.2 Container integrity
4.2.1 Container Closure Integrity (CCI)
Container closure integrity shall be ensured until first intentional user interaction which breaks CCI.
If the NIS is manufacturer-assembled with a Primary Container Closure (PCC) to form a single integral
unit, the manufacturing processes, including assembly, shall be shown to not adversely impact container
closure integrity, in accordance with applicable pharmacopeia.
4.2.2 Resealability — All multi-dose cartridges or reservoirs with discs
For all cartridges or reservoirs with discs intended for multiple penetrations, after having been
penetrated in accordance with the test method specified in 5.1, the penetrated discs of 20 cartridges or
reservoirs shall not leak from the penetration site when the cartridge is pressurized.
The resealable disc of the cartridge or reservoir shall be punctured 1,0 times the maximum number of
penetrations expected during its intended use.
4.2.3 Fragmentation (disc coring) – cartridges or reservoirs with discs
Cartridges or reservoirs that are accessed through an elastomeric disc (barrier) with a needle, spike
or other access device for delivery shall not exceed six elastomeric disc fragments in the visible range
(>150 µm in diameter) per 100 punctures in accordance with the method described in 5.2, collected
from both coring (ejected from the needle) and fragmentation (collected from the liquid in the container
or reservoir).
For multi-dose cartridges or reservoirs, each disc (barrier) shall be punctured 1.0 times the maximum
number of penetrations expected during its intended use.
Risk assessment shall assess the impact of fragments on the function of the NIS to determine if
additional mitigations or lowering the limit of allowed fragments are required.
NOTE The impact of any fragments on the function of the NIS can be assessed through dose accuracy testing.
4.3 Cannula requirements (as part of the fluid path)
4.3.1 Rigid needles
If the integrated fluid path contains a rigid needle, the strength of union between the needle at its
connection point to the NIS shall not break when an attachment force given in ISO 7864:2016, Table
2 is applied as tension. The directions of force shall be applied as the needle would encounter during
removal from the injection site.
For tapered needles, the minimum force given in ISO 7864:2016, Table 2 is determined by the outer
diameter at the hub as indicated in ISO 7864:2016, Figure 1.
The performance of the rigid needle part shall fulfil the requirements in ISO 9626:2016, Clause 5 and
ISO 7864:2016, 4.10.4, 4.11, 4.12 and 4.13, or an equivalent and applicable standard for tubing suited to
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medical use but fabricated in materials other than stainless steel, to ensure the rigid needle performs
as intended for the specific design.
4.3.2 Soft cannulas
If the integrated fluid path contains a soft cannula and an introducer needle, the strength of union
between the soft cannula and NIS, or the introducer needle and the NIS, shall meet the requirements
of ISO 10555-5:2013, 4.3.3.4 to ensure the soft cannula and/or introducer needle remains affixed to the
NIS throughout its intended use. The testing shall consider and address the forces and vectors that the
introducer needle and cannula would encounter during removal from the injection site.
In addition, the soft cannula shall meet the requirements of ISO 10555-1:2013, 4.6 to ensure the soft
cannula performs as intended for the specific design. Additional physical and functional evaluations to
be considered may include flexural fatigue, compression force, kink resistance, burst testing, etc. Risk
assessment shall be relied upon to determine appropriate evaluations.
In addition, Annex A of this document may also be of assistance.
4.4 Fluid line connections
If the NIS requires a separate external fluid line to connect the functional core of the NIS to a distant
injection site, any connections along that fluid line shall withstand a static tensile force of not less than
15N for 15 seconds.
If the connection uses a standard luer lock connection, the connector shall comply with ISO 80369-7.
4.5 Medicinal product compatibility
4.5.1 General
All materials of the NIS in direct contact with the medicinal product shall be compatible with the
medicinal product to be delivered with the NIS.
When the NIS is filled by the manufacturer, and the container and/or the integrated fluid path are
designed to protect the medicinal product through shipment and storage, it is considered part of the
primary container closure. The requirements for assessing the adequacy of the PCC is covered by
pharmacopeia and ICH Guidance and are not addressed within this document.
Annex A provides a reference to some relevant regulations, guidance, standards or compendia material
for each topic below.
4.5.2 Medicinal product compatibility with reservoir and integrated fluid path materials
Reservoir and integrated fluid path materials that come into contact with the medicinal product
shall not adversely affect the quality of the medicinal product for the intended time of contact. These
requirements apply to the medicinal product after delivery through the NIS. Annex E provides a
discussion of medicinal product compatibility.
4.5.3 Reservoir and integrated fluid path particulate matter
4.5.3.1 General
The reservoir and/or integrated fluid path shall be assessed for sub-visible and visible particulate matter.
Applicable pharmacopeia establishes limits for the size and number of particulates allowed for
the medicinal product. A portion or subset of the particulate matter limit may be generated by the
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reservoir and/or fluid path during delivery. Manufacturers shall establish particulate matter limits of
the reservoir and/or fluid path based on risk assessment and applicable pharmacopeia.
NOTE 1 It is recommended that the manufacturer and the customer agree upon the test methods to be used
and the allocation of size and number of sub-visible and visible particulate matter permissible for the NIS.
Particulates, which, due to their size, nature and/or quantity interfere with the function of the NIS,
medicinal product compatibility or have a negative impact to patient safety, are not acceptable.
NOTE 2 The impact of any particulates on the function of the NIS can be assessed through dose accuracy
testing.
4.5.3.2 Sub-visible
Unless otherwise justified, limits for the NIS reservoir and/or integrated fluid path shall be:
— Particles ≥10µm: 600 max. per NIS
— Particles ≥25µm: 60 max. per NIS
when tested, for example, in accordance with the method described in 5.3.
NOTE These above listed limits are taken from ISO 11040-4:2015.
4.5.3.3 Visible
Visible particulate matter (>150µm in diameter) for the NIS reservoir and/or integrated fluid path shall
not be present when teste
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