EN ISO 11608-1:2022
(Main)Needle-based injection systems for medical use - Requirements and test methods - Part 1: Needle-based injection systems (ISO 11608-1:2022)
Needle-based injection systems for medical use - Requirements and test methods - Part 1: Needle-based injection systems (ISO 11608-1:2022)
This document specifies requirements and test methods for Needle-Based Injection Systems (NISs) for single-patient use intended to deliver discrete volumes (bolus) of medicinal product, which can be delivered through needles or soft cannulas for intradermal, subcutaneous and/or intramuscular delivery, incorporating pre-filled or user-filled, replaceable or non-replaceable containers.
This document applies in cases where the NIS incorporates a prefilled syringe. However, stand-alone prefilled syringes defined by ISO 11040-8 are not covered by this document (see exclusions below).
It is important to note that other functions and characteristics of the prefilled syringe, such as dose accuracy, are subject to the requirements (delivered volume) in ISO 11040-8 and not this document, unless the addition impacts the delivery function (e.g. a mechanism that intends to restrict or stop the plunger movement, which would limit the dose delivered). In that case, the system is completely covered by this document and applicable requirements of the ISO 11608 series.
Excluded from the scope are:
— stand-alone prefilled syringes defined by ISO 11040-8 (with noted exceptions above);
— NISs that provide continuous delivery and require a delivery rate clinically specified in the medicinal product labelling or determined by a physician based on clinical relevance (i.e. medication efficacy) as would be the case with insulin patch pumps or traditional infusion pumps (e.g. IEC 60601-2-24, ISO 28620) associated with continuous delivery of medicinal products (e.g. insulin);
— NISs with containers that can be refilled multiple times;
— requirements relating to methods or equipment associated with user filling of containers unless they are dedicated accessories (a component necessary for primary function, whether included in the original kitted product or not);
— NISs intended for dental use;
— NISs intended for different routes of administration (e.g. intravenous, intrathecal, intraocular).
NOTE These products that are excluded might benefit from elements in this document but might not completely fulfil the basic safety and effectiveness of such products.
Kanülenbasierte Injektionssysteme zur medizinischen Verwendung - Anforderungen und Prüfverfahren - Teil 1: Kanülenbasierte Injektionssysteme (ISO 11608-1:2022)
Dieses Dokument legt Anforderungen und Prüfverfahren für kanülenbasierte Injektionssysteme (en: needle-based injections systems, NISs) fest, die zur Verwendung bei nur einem Patienten zur Abgabe eines diskreten Volumens (Bolus) eines Arzneimittels vorgesehen sind; die Abgabe kann dabei mit Kanülen oder weichen Kanülen für die intradermale, subkutane und/oder intramuskuläre Abgabe erfolgen und in den Systemen sind vorgefüllte oder durch den Benutzer befüllte, austauschbare oder nicht austauschbare Behälter eingebaut.
Dieses Dokument ist anwendbar für Fälle, bei denen eine vorgefüllte Spritze im NIS eingebaut ist. Allerdings sind eigenständige vorgefüllte Spritzen, wie durch ISO 11040 8 definiert, nicht durch dieses Dokument abgedeckt (siehe die unten aufgeführten Ausschlüsse).
Es ist wichtig zu beachten, dass andere Funktionen und Merkmale der vorgefüllten Spritze, beispielsweise die Dosiergenauigkeit, den Anforderungen (an das abgegebene Volumen) in ISO 11040 8 und nicht dieses Dokuments unterliegen, es sei denn, die Ergänzung wirkt sich auf die Abgabefunktion aus (z. B. ein Mechanismus, der bestimmungsgemäß die Kolbenbewegung einschränkt oder stoppt, wodurch die abgegebene Dosis begrenzt würde). In diesem Fall fällt das System vollständig unter dieses Dokument und die anwendbaren Anforderungen der Normenreihe ISO 11608.
Ausgeschlossen vom Anwendungsbereich sind:
— eigenständige vorgefüllte Spritzen, wie durch ISO 11040 8 definiert (mit den oben erwähnten Ausnahmen);
— NISs, die eine kontinuierliche Abgabe liefern und eine Abgaberate erfordern, die in der vom Hersteller bereitgestellten Information des Arzneimittels klinisch festgelegt oder von einem Arzt, beruhend auf der klinischen Relevanz (d. h. der Wirksamkeit der Medikation), bestimmt wird, wie dies bei Insulin-Patch-Pumpen oder herkömmlichen Infusionspumpen (z. B. IEC 60601 2 24, ISO 28620), die mit einer kontinuierlichen Abgabe von Arzneimitteln (z. B. von Insulin) verbunden sind, der Fall wäre;
— NISs mit Behältern, die mehrere Male befüllt werden können;
— Anforderungen in Bezug auf Verfahren oder Vorrichtungen im Zusammenhang mit dem Füllen von Behältern durch den Benutzer, es sei denn es handelt sich um vorgesehene Zubehörteile (eine für die Primärfunktion notwendige Komponente, die in der Ausstattung des Originalprodukts enthalten ist oder nicht);
— zum zahnärztlichen Gebrauch vorgesehene NISs;
— NISs, die für andere Verabreichungswege (z. B. intravenös, intrathekal, intraokular) bestimmt sind.
ANMERKUNG Diese ausgeschlossenen Produkte könnten von Elementen in diesem Dokument profitieren, könnten aber auch die Basissicherheit und Wirksamkeit solcher Produkte nicht vollständig erfüllen.
Systèmes d'injection à aiguille pour usage médical - Exigences et méthodes d'essai - Partie 1: Systèmes d'injection à aiguille (ISO 11608-1:2022)
Le présent document spécifie les exigences et les méthodes d'essai relatives aux systèmes d'injection à aiguille (NIS) à usage unique destinés à administrer des volumes discrets (bolus) de médicament, qui peuvent être administrés au moyen d'aiguilles ou de canules souples pour l'administration intradermique, sous-cutanée et/ou intramusculaire, comprenant des conteneurs préremplis ou remplis par l'utilisateur, remplaçables ou non remplaçables.
Le présent document s'applique dans les cas où le NIS intègre une seringue préremplie. Toutefois, les seringues préremplies autonomes définies par l'ISO 11040-8 ne sont pas couvertes par le présent document (voir les exclusions ci-dessous).
Il est important de noter que les autres fonctions et caractéristiques de la seringue préremplie, comme la précision de dosage, sont soumises aux exigences (volume administré) de l'ISO 11040-8 et non à celles du présent document, à moins que l'ajout n'affecte la fonction d'administration (par exemple, un mécanisme destiné à restreindre ou à arrêter le mouvement du piston, limitant ainsi la dose administrée). Dans ce cas, le système est entièrement couvert par le présent document et les exigences applicables de la série de normes ISO 11608.
Les éléments suivants sont exclus du domaine d'application:
— les seringues préremplies autonomes définies par l'ISO 11040-8 (à l'exception des éléments mentionnés ci-dessus);
— les NIS qui permettent une administration en continu et nécessitent un débit d'administration cliniquement spécifié sur l'étiquetage du médicament ou déterminé par un médecin sur la base de la pertinence clinique (c'est-à-dire l'efficacité du médicament), comme ce serait le cas avec des pompes «patch» à insuline ou des pompes à perfusion traditionnelles (par exemple l'IEC 60601-2-24, l'ISO 28620) associées à une administration en continu (par exemple, insuline);
— les NIS avec des conteneurs qui peuvent être remplis plusieurs fois;
— les exigences relatives aux méthodes ou à l'équipement associés au remplissage des conteneurs par l'utilisateur, à moins qu'il ne s'agisse d'accessoires dédiés (un composant nécessaire à une fonction principale, qu'il soit inclus ou non dans le produit en kit d'origine);
— les NIS destinés à un usage dentaire;
— les NIS destinés à des voies d'administration différentes (par exemple, intraveineuses, intrathécales, intraoculaires).
NOTE Ces produits exclus peuvent bénéficier d'éléments issus du présent document, mais peuvent ne pas répondre entièrement aux exigences de base en matière de sécurité et d'efficacité pour les produits concernés.
Peresa za injiciranje za uporabo v medicini - Zahteve in preskusne metode - 1. del: Peresa za injiciranje (ISO 11608-1:2022)
Ta dokument določa zahteve in preskusne metode za peresa za injiciranje (NIS) za uporabo pri enem bolniku, ki so namenjena ločenemu dovajanju odmerkov (bolusov) zdravila, ki ga je mogoče dovajati prek igle ali mehke kanile za intradermalno, subkutano in/ali intramuskularno injiciranje, ter vključujejo predhodno napolnjene vsebnike, vsebnike, ki jih polni uporabnik, zamenljive ali nezamenljive vsebnike.
Ta dokument se uporablja v primerih, ko peresa za injiciranje vključujejo predhodno napolnjeno injekcijsko brizgo. Ne obravnava pa samostojnih predhodno napolnjenih injekcijskih brizg, opredeljenih v standardu ISO 11040-8 (glej spodnje izključitve). Poudariti je treba, da za druge funkcije in lastnosti predhodno napolnjene injekcijske brizge, kot je natančnost odmerka, veljajo zahteve (dovedena količina) iz standarda ISO 11040-8 in ne zahteve iz tega dokumenta, razen če dodatna lastnost vpliva na funkcijo dovajanja zdravila (npr. mehanizem, predviden za zaustavljanje bata, ki omejuje dovedeni odmerek). V tem primeru se za sistem v celoti uporabljajo ta dokument in ustrezne zahteve skupine standardov ISO 11608.
Na področje uporabe tega dokumenta ne spadajo:
– samostojne predhodno napolnjene injekcijske brizge, opredeljene v standardu ISO 11040-8 (razen zgoraj navedenih izjem);
– peresa za injiciranje, ki zagotavljajo neprekinjeno dovajanje in za katere se zahteva hitrost dovajanja, ki je klinično določena na
oznakah zdravila ali jo določi zdravnik na podlagi klinične ustreznosti (tj. učinkovitost zdravila),
kot je to na primer predvideno za inzulinske črpalke z obližem ali običajne infuzijske črpalke (npr. IEC 60601-2-24,
ISO 28620), na katere se navezuje neprekinjeno dovajanje zdravil (npr. inzulina);
– peresa za injiciranje z vsebniki, ki jih je mogoče napolniti večkrat;
– zahteve v zvezi z metodami ali opremo, ki se navezujejo na polnjenje vsebnikov s strani uporabnikov, razen če
gre za namenske pripomočke (npr. sestavni del, ki je potreben za zagotavljanje primarne funkcije, ne glede na to, ali je priložen
v izvornem kompletu proizvoda ali ne);
– peresa za injiciranje, namenjena zobozdravstveni uporabi;
– peresa za injiciranje, namenjena za druge poti dovajanja (npr. intravenozno, intratekalno, intraokularno).
OPOMBA: Nekateri elementi tega dokumenta bi lahko bili uporabni za proizvode, ki so izključeni s področja njegove uporabe, vendar
pa ne zajemajo vseh osnovnih zahtev za varnost in učinkovitost takih proizvodov.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
01-julij-2022
Nadomešča:
SIST EN ISO 11608-1:2015
Peresa za injiciranje za uporabo v medicini - Zahteve in preskusne metode - 1. del:
Peresa za injiciranje (ISO 11608-1:2022)
Needle-based injection systems for medical use - Requirements and test methods - Part
1: Needle-based injection systems (ISO 11608-1:2022)
Kanülenbasierte Injektionssysteme zur medizinischen Verwendung - Anforderungen und
Prüfverfahren - Teil 1: Kanülenbasierte Injektionssysteme (ISO 11608-1:2022)
Systèmes d'injection à aiguille pour usage médical - Exigences et méthodes d'essai -
Partie 1: Systèmes d'injection à aiguille (ISO 11608-1:2022)
Ta slovenski standard je istoveten z: EN ISO 11608-1:2022
ICS:
11.040.25 Injekcijske brizge, igle in Syringes, needles an
katetri catheters
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
EN ISO 11608-1
EUROPEAN STANDARD
NORME EUROPÉENNE
May 2022
EUROPÄISCHE NORM
ICS 11.040.25 Supersedes EN ISO 11608-1:2015
English Version
Needle-based injection systems for medical use -
Requirements and test methods - Part 1: Needle-based
injection systems (ISO 11608-1:2022)
Systèmes d'injection à aiguille pour usage médical - Kanülenbasierte Injektionssysteme zur medizinischen
Exigences et méthodes d'essai - Partie 1: Systèmes Verwendung - Anforderungen und Prüfverfahren - Teil
d'injection à aiguille (ISO 11608-1:2022) 1: Kanülenbasierte Injektionssysteme (ISO 11608-
1:2022)
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 11608-1:2022 E
worldwide for CEN national Members.
Contents Page
European foreword . 3
European foreword
This document (EN ISO 11608-1:2022) 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 May 2025.
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 11608-1:2015.
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 11608-1:2022 has been approved by CEN as EN ISO 11608-1:2022 without any
modification.
INTERNATIONAL ISO
STANDARD 11608-1
Fourth edition
2022-04
Needle-based injection systems for
medical use — Requirements and test
methods —
Part 1:
Needle-based injection systems
Systèmes d'injection à aiguille pour usage médical — Exigences et
méthodes d'essai —
Partie 1: Systèmes d'injection à aiguille
Reference number
ISO 11608-1:2022(E)
ISO 11608-1:2022(E)
© 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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ISO 11608-1:2022(E)
Contents Page
Foreword .v
Introduction .vii
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Symbols . 5
5 Requirements . 6
5.1 General . 6
5.2 System designations . 7
5.3 Risk approach . 8
5.4 Usability engineering . . 8
5.5 Uncertainty of measurement and conformance with specifications . 8
5.6 General design requirements . 9
5.7 Design verification . 11
5.7.1 General . 11
5.7.2 Primary functions requirements. 11
6 Reagent and apparatus .12
6.1 General .12
6.2 Test liquid .13
6.3 Test surface for free-fall testing . 13
7 Assessment of dose accuracy and other primary functions .13
7.1 General .13
7.2 Dose accuracy .13
7.2.1 General .13
7.2.2 Dosing regions . 14
7.2.3 Dose settings . 14
7.3 Sampling for other primary functions . 16
7.4 Assessment . 16
7.4.1 General . 16
7.4.2 Determination of dose accuracy limits . 16
7.4.3 Determination of last-dose error and last-dose accuracy limits (system
designations A and C) . 18
7.4.4 Calculation of dose delivery efficiency (system designations B1 and D1,
user-filled). 19
7.4.5 Acceptance criteria . 19
8 Preparation and operation of NISs .20
9 Test case matrix .20
10 Testing procedures .22
10.1 General .22
10.2 Normal/anticipated condition test cases . 22
10.2.1 Cool, standard and warm atmosphere in-use testing .22
10.2.2 Last-dose accuracy testing (system designations A and C only) .23
10.2.3 Life-cycle testing (systems designations A and B only) — Preconditioning .23
10.3 Stressed/challenge condition test cases . 23
10.3.1 Free fall testing – Preconditioning . 23
10.3.2 Dry-heat storage – Preconditioning . 25
10.3.3 Cold-storage - Preconditioning . 25
10.3.4 Damp-heat testing (system designations A and B only) — Preconditioning .26
10.3.5 Cyclical testing (system designations A and B only) — Preconditioning .26
10.3.6 Vibration testing — Preconditioning . 26
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ISO 11608-1:2022(E)
10.3.7 Transport – Preconditioning . 27
10.3.8 Functional stability – Preconditioning . 27
10.3.9 Fluid leakage (system designations A and B only) - Preconditioning . 27
11 Inspection .28
11.1 General .28
11.2 Legibility of markings .28
11.3 Freedom from defects .28
12 Information supplied with the NIS .29
12.1 General .29
Annex A (informative) Testing rationale .30
Annex B (normative) One- and two-sided tolerance limit factors, k (for normally distributed
data) . .35
Annex C (informative) Biological evaluation according to ISO 10993-1 .46
Annex D (informative) Functional stability .48
Annex E (normative) Instructions for use, marking and age warning .50
Annex F (informative) Rationale for recommended sample sizes .52
Annex G (informative) Considerations for assessing impact on primary functions due to
exposure to or contact with medicinal product .57
Annex H (informative) Introduction of primary functions .59
Bibliography .68
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ISO 11608-1:2022(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 fourth edition cancels and replaces the third edition (ISO 11608-1:2014), which has been
technically revised.
The main changes are as follows:
— relocation of content to the other parts of the ISO 11608 series, as appropriate (see Figure 1);
— added language to address the case when a platform NIS is applied for different therapeutics or
users;
— clarified that the “user” referenced in this document is the patient receiving the therapeutic, and not
the health care professional who prescribes the medication (see Clause 1);
— defined “bolus”, and confirmed that this document is focused on bolus (fixed dose) delivery (not
basal bolus), so as to distinguish from the definition in IEC 60601-2-24 (see Clause 1);
— clarified the references to ISO 13485, ISO 14971 and IEC 62366-1 (see 5.1.2, 5.3 and 5.4, respectively)
and exclude any reference to an equivalent standard;
— elimination of the term “essential performance” and defined “primary functions” - those functions
for which failure would “directly” result in “new and unacceptable harm”. This is to eliminate
confusion with use of the term essential performance in IEC 60601-1 (see 5.7.2, Clause 7 and
Annex H). Further, there is a focus on “unacceptable harm” and not just “risk”;
— clarification of the recommendations for sample sizes for primary functions (Clause 7), simplified
the number of rules from 3 to 2 (see 7.4.2.1), and updated the recommended sample sizes (see
Table 3), but confirmed that different sample sizes can be chosen, if justified [see Clause 9 g)];
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ISO 11608-1:2022(E)
— the rationale for different sample sizes for free fall testing between system designations A/B and
C/D was clarified (see 10.3.1 and Annex A);
— differentiated lighting levels for user legibility – the ability of the user to read the labelling in normal
use conditions (see 11.2) and inspection for defects (see 11.3);
— rationales in Annex A were expanded to address clauses throughout the document.
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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ISO 11608-1:2022(E)
Introduction
This document covers needle-based injection systems (referred to as NISs) intended for human
use. It provides performance requirements and characteristics so that variations of design are not
unnecessarily restricted. The document does not cover needle-free injectors.
Because of the anticipated variation in the designs of NISs, this document tends to specify the results of
the design effort instead of the physical and construction requirements used as the basis for NIS design.
The ISO 11608 series deals with “hand-held” or “on-body” delivery systems (OBDSs). By hand-held,
users (patients or caregivers) control and stabilize the NIS at the injection site during administration
of a discrete volume. Delivery times for this type of NIS would, therefore, be limited to avoid instability
and the potential for injection site trauma. For NISs with larger delivery volumes or physical properties
requiring a longer time to deliver, OBDS might be more practical. The OBDS would likely exist as either
“body-worn” (directly anchored to the body, e.g. using adhesive) or “patient-worn” (indirectly anchored,
e.g. catheter attached to OBDS contained in a back-pack or pocket). In either configuration, the time or
speed employed to deliver a discrete volume would be based upon tolerability or convenience rather
than clinical relevance (e.g. medication efficacy) as would be the case with insulin patch pumps or
traditional infusion pumps (e.g. IEC 60601-2-24, ISO 28620) associated with continuous delivery (e.g.
insulin). However, while this document is not intended to directly apply to these pump products, it does
contain requirements and tests methods that can be used to help design and evaluate them.
The ISO 11608 series includes requirements for design verification of the NIS’s conformance with
its design specification. The sampling plans, preconditioning criteria and other aspects of testing
specified in these documents are intended to verify the design at a high confidence level. They are not
intended to stipulate lot release acceptance criteria (AQL, p-content, probability, etc.) associated with
a manufacturing process. The ISO 11608 series includes other aspects beyond dose accuracy. Finally, it
develops the requirement for functional stability and offers additional statistical approaches (e.g. use of
variable and attribute data) in satisfying the various NIS design verification requirements.
Figure 1 illustrates the correlations between the different parts in the ISO 11608 series and other
applicable standards.
vii
ISO 11608-1:2022(E)
Figure 1 — ISO 11608 series road map
The design requirements related to system function are presented as to assist manufacturers during
the design phase. However, these design requirements do not replace system testing of the components
viii
ISO 11608-1:2022(E)
and, where possible, direct communication and/or quality agreements between system component
manufacturers.
Materials to be used for construction are not specified, as their selection will depend on the design, the
intended use and the process of manufacture used by individual manufacturers.
There are other international and national standards, guidance publications and, in some countries,
national regulations that are applicable to medical devices and pharmaceuticals. Developers and
manufacturers of NISs are encouraged to investigate and determine whether there are any other
requirements relevant to the suitability and safety of their products.
This document is written with the understanding that each system will be verified and validated for
each therapeutic or medicinal product for which it is intended to be used. If the same system is able to,
with no or minimal changes, deliver more than one therapeutic or medicinal product, due to the nature
and uniqueness of the combination of the delivery system and therapeutic or medicinal product, it will
be considered another product and each combination should be addressed individually in accordance
with the requirements of this document. This does not preclude leveraging information and data across
systems as long as there is sufficient information to support the unique combination under development.
Finally, manufacturers are expected to follow a risk-based approach during the design, development,
and manufacture of the NIS. Given that each product can deliver different medicinal products and/or
have a different intended use, this can result in product-specific requirements and test methods that
differ from what is outlined in this document. It is expected that a risk management process is applied
to justify and document:
— any exclusions/deviations from requirements, specifications, methods or limits contained in
or referenced in this document when they are not directly applicable and/or appropriate to the
system. These new or modified requirements can be more or less restrictive as they are unique to
the specific NIS (including the medicinal product); and
— any substitutions or omissions of requirements, specifications, methods or limits unique to each
specific NIS (including the medicinal product), when those provided in this document are not
applicable and/or appropriate to the NIS.
The flexibility provided in this document allows it to be applied to many different device and medicinal
product combinations. However, it makes it difficult to make a general declaration of conformance to
the document. As such, when making any declaration of conformance to this document, specify these
deviations, exclusions, substitutions, and omissions supported by adequate justification in the design
file.
ix
INTERNATIONAL STANDARD ISO 11608-1:2022(E)
Needle-based injection systems for medical use —
Requirements and test methods —
Part 1:
Needle-based injection systems
1 Scope
This document specifies requirements and test methods for Needle-Based Injection Systems (NISs)
for single-patient use intended to deliver discrete volumes (bolus) of medicinal product, which can
be delivered through needles or soft cannulas for intradermal, subcutaneous and/or intramuscular
delivery, incorporating pre-filled or user-filled, replaceable or non-replaceable containers.
This document applies in cases where the NIS incorporates a prefilled syringe. However, stand-alone
prefilled syringes defined by ISO 11040-8 are not covered by this document (see exclusions below).
It is important to note that other functions and characteristics of the prefilled syringe, such as dose
accuracy, are subject to the requirements (delivered volume) in ISO 11040-8 and not this document,
unless the addition impacts the delivery function (e.g. a mechanism that intends to restrict or stop
the plunger movement, which would limit the dose delivered). In that case, the system is completely
covered by this document and applicable requirements of the ISO 11608 series.
Excluded from the scope are:
— stand-alone prefilled syringes defined by ISO 11040-8 (with noted exceptions above);
— NISs that provide continuous delivery and require a delivery rate clinically specified in the medicinal
product labelling or determined by a physician based on clinical relevance (i.e. medication efficacy)
as would be the case with insulin patch pumps or traditional infusion pumps (e.g. IEC 60601-2-24,
ISO 28620) associated with continuous delivery of medicinal products (e.g. insulin);
— NISs with containers that can be refilled multiple times;
— requirements relating to methods or equipment associated with user filling of containers unless
they are dedicated accessories (a component necessary for primary function, whether included in
the original kitted product or not);
— NISs intended for dental use;
— NISs intended for different routes of administration (e.g. intravenous, intrathecal, intraocular).
NOTE These products that are excluded might benefit from elements in this document but might not
completely fulfil the basic safety and effectiveness of such products.
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 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
ISO 14971:2019, Medical devices — Application of risk management to medical devices
ISO 11608-1:2022(E)
ISO 16269-6, Statistical interpretation of data — Part 6: Determination of statistical tolerance intervals
ISO 23908, Sharps injury protection — Requirements and test methods — Sharps protection features for
single-use hypodermic needles, introducers for catheters and needles used for blood sampling
IEC 60529, Degrees of protection provided by enclosures (IP Code)
IEC 62366-1, Medical devices — Part 1: Application of usability engineering to medical devices
IEC 60068-2-6:2007, Environmental testing – Part 2-6: Tests – Test Fc: Vibration (sinusoidal)
3 Terms and definitions
For the purposes of this document, the following terms and definitions 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
accessory
article or supplementary part used in conjunction with a needle-based injection system (3.15)
3.2
bolus
discrete quantity of medicinal product
3.3
container
component(s) of the needle-based injection system (3.15) used to hold the medicinal product
Note 1 to entry: Containers can be integrated into the needle-based injection system (3.15) at the point of
manufacture or assembled into the needle-based injection system (3.15) at the time of use.
Note 2 to entry: The container can be the primary container closure (3.17) if provided pre-filled by the
manufacturer or a reservoir (3.20) if filled at the time of use.
3.4
deliverable volume
contents of the container (3.3) that can be expelled by operating the needle-based injection system (3.15)
in according to the instructions for use (3.10)
Note 1 to entry: Deliverable volume can be less than the fill volume.
3.5
design specification
functional, performance, usability or safety characteristic of a needle-based injection system (3.15),
developed from design inputs, that is confirmed during design verification
Note 1 to entry: The focus of this document is design verification; it does not specify how to perform design
validation.
3.6
dose delivery efficiency
ratio of expelled volume to fill volume
Note 1 to entry: Delivery efficiency can be used to evaluate dose accuracy (3.7) for needle-based injection systems
(3.15) designed to fully empty single-dose containers (3.3) filled by the user.
ISO 11608-1:2022(E)
3.7
dose accuracy
difference between the intended dose and the delivered dose
3.8
fluid path
pathway the medicinal product follows from the container (3.3) to the targeted delivery site
Note 1 to entry: This can include a reservoir (3.20).
3.9
functional stability
ability of a needle-based injection system (3.15) to maintain its primary function (3.18) over a specified
period of time and/or number of actuations
Note 1 to entry: See Annex D for further information.
3.10
instructions for use
IFU
directions provided by the manufacturer for the correct handling and operation of the needle-based
injection system (3.15)
3.11
intended dose
amount of medicinal product intended to be delivered at one time
3.12
in-use life
period of time or number of actuations during which the needle-based injection system (3.15) maintains
primary functions (3.18), when used according to the instructions for use (3.10)
Note 1 to entry: For system designations A and B, this might be defined by battery life, total number of doses
delivered or a combination of these or other factors.
Note 2 to entry: For system designations C and D from first breach of sterility/primary container closure (3.17)
through its last dose delivered.
3.13
manufacturer-filled
pre-filled with the medicinal product by the manufacturer
Note 1 to entry: See also primary container closure (3.17). See ISO 11608-3:2022, Annex F.
Note 2 to entry: This medicinal product can be in liquid form or lyophilized form with diluent.
3.14
minimum deliverable dose
for needle-based injection system (3.15) with system designations B1 and D1 filled by the manufacturer,
the minimum dose the system is capable of delivering
3.15
needle-based injection system
NIS
injection system intended for parenteral administration of medicinal products using a needle or
cannula and a multi-dose or single-dose container
ISO 11608-1:2022(E)
3.16
pre-set dose
individual amount of medicinal product selected for injection ahead of the use of the needle-based
injection system (3.15)
Note 1 to entry: The doses can be pre-set by the manufacturer or the user.
3.17
primary container closure
PCC
container (3.3) in direct contact with the medicinal product whose primary purpose is to contain and
protect the medicinal product during transportation, storage and use
Note 1 to entry: The PCC is manufacturer-filled (3.13).
3.18
primary function
function or operation of the needle-based injection system (3.15), which, if it does not perform to
specifications during use, would directly result in a failure to accurately deliver the medicinal product
via the correct route and/or directly result in unacceptable harm to the patient
Note 1 to entry: At a minimum, this includes the dose delivery function, achieved through assessment of dose
accuracy (3.7). See also 5.7.2.
Note 2 to entry: Primary function is related to the definition of "essential performance" in IEC 60601-1, but
differs in the following ways:
— accurate delivery of the medicinal product via the correct route, i.e. clinical function, independent of the
potential for harm to the patient; and
— functions and operations where a failure can cause a situation where the product can directly cause
unacceptable harm to the patient, even if these would be considered “basic safety” in IEC 60601-1.
Note 3 to entry: See Annex H.
3.19
priming
actions that make the dosing mechanism of the needle-based injection system (3.15) ready for use
EXAMPLE Removing air from the fluid path.
3.20
reservoir
container (3.3) supplied empty that is in direct contact with the medicinal product once filled by the
user
Note 1 to entry: The reservoir's primary purpose is to contain the medicinal product prior to the initiation of
delivery.
Note 2 to entry: See ISO 11608-3:2022, Annex F.
3.21
residual volume
volume of medicinal product remaining within the needle-based injection system (3.15), after dose
delivery has been completed
Note 1 to entry: In the case of a needle-based injection system (3.15) that incorporates a connecting pathway to a
separate, non-integral needle or cannula, the residual volume will include the volume within the said connecting
pathway [this applies to both single-use and re-usable needle-based injection systems (3.15)].
3.22
residual scale
scale that indicates the remainder of medicinal product in the container (3.3)
ISO 11608-1:2022(E)
3.23
shelf life
maximum length of time (usually measured in months or years) from the point of manufacture to
release into the supply chain up to the point of first use
3.24
system designation
means of delineating different types of needle-based injection system (3.15) by whether the (medication)
container (3.3) is replaceable or non-replaceable, and if that container is intended to contain multiple
doses or a single dose
Note 1 to entry: See Table 1 for system designations.
3.25
user-filled
filled via a manual or automated process by the user from a separate medicinal product or diluent
container, or reconstituted (e.g. if in lyophilized form)
4 Symbols
P Measured value of parameter of interest other than dose accuracy
meas
P Parameter of interest other than dose accuracy (e.g. dialling torque)
set
V One of any pre-set doses (expressed as a volume, in millilitres) used in determining the dose
set
accuracy for a given NIS
V The volumetric measurement value for a given V , expressed in millilitres
meas set
G The gravimetric measurement value for a given V , expressed in grams
meas set
ρ Density, expressed in grams per millilitre
p Probability content
Y Number of NISs required for a given test
R Replicate, a random sequence of different dose volumes tested
n Number of measurements
x
The sample mean; when based on a random sample, an estimate of the true mean
s The sample standard deviation; when based on a random sample, an estimate of the true stand-
ard deviation
k k value, or tolerance limit factor, determined from the confidence level (95 %), probability content,
p, and number of measurements, n, conducted. The k-value is found in Annex B
R Dialling resolution, the minimum dose setting increment of the NIS
D
α Absolute error, in millilitres, used to define the upper and lower specification limits for a pre-set
dose in absolute terms
β Relative error, as a percentage, used to define the upper and lower specification limits for a pre-
set dose in relative terms
P The transition point volume, in millilitres, at which the upper and lower specification limits for
T
V change from absolute terms to relative terms:
set
ISO 11608-1:2022(E)
P = (100 ×α)/β
T
P Upper specification limit for a given P
USL set
P Lower specification limit for a given P
LSL set
V Upper specification limit for a given V
USL set
V Lower specification limit for a given V
LSL set
5 Requirements
5.1 General
5.1.1 This document addresses requirements for the NIS as a system.
5.1.2 For the design and development of the NIS, a QMS such as ISO 13485:2016, 7.3 can be used.
5.1.3 Prior to design verification, the manufacturer shall establish the NIS design specification by
considering the characteristics required for both the NIS (e.g. actuation spring force, material selection)
and medicinal product (e.g. shear, formulation viscosity, storage temperature, expiration dating). Once
the design specification is established and representative samples have been fabricated, NIS design
verification, in accordance with this document, shall be conducted.
Figure 2 represents the relationship of this document with the design and development processes.
ISO 11608-1:2022(E)
Figure 2 — Design verification flow
5.1.4 The manufacturer shall confirm that the materials of construction are appropriate for use by
the intended user population and materials selected are compatible with the medicinal product.
NOTE Assessment of compatibility of materials of construction is addressed in other documents.
5.2 System designations
Given the differences in NIS designs and containers (e.g. multi-dose, single-dose with partial
evacuation, and single-dose with full evacuation), the following system designations are provided
to clearly associate the appropriate test and dose accuracy method with the injection system under
consideration. Containers can be either manufacturer-filled or user-filled. Table 1 shows the various
NIS system designations.
ISO 11608-1:2022(E)
Table 1 — System designations
Multi-dose container Single-dose container
NIS with replaceable container A B1
Each container holds multiple doses, Each container holds a single dose,
the size of which may be fixed or and the entire deliverable volume is
variable (set by the user) ex
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