SIST EN ISO 21649:2023
(Main)Needle-free injection systems for medical use - Requirements and test methods (ISO 21649:2023)
Needle-free injection systems for medical use - Requirements and test methods (ISO 21649:2023)
This document applies to safety and performance and testing requirements for single-use and multiple-use Needle-Free Injection Systems (NFISs) intended for human use in clinics and other medical settings and for personal use by patients.
The dose chamber of the NFIS is often disposable and intended to be replaced after either a single use or a limited number of uses. It is sometimes separable from the injection mechanism and often termed a “cartridge”, “ampoule”, “syringe”, “capsule” or “disc”. In contrast, the dose chamber can also incorporate a permanent internal chamber designed to last through the claimed life of the device, and an additional member or members which eliminate the risk of cross-contamination.
Excluded from this document are drug delivery methods which:
— involve penetration of a part of the device itself into or through skin or mucous membranes (such as needles, tines, micro-needles, implantable slow-release drug devices);
— generate aerosols, droplets, powders or other formulations for inhalation, insufflation, intranasal or oral deposition (such as sprays, inhalers, misters);
— deposit liquids, powders, or other substances on the surface of skin or mucosal surfaces for passive diffusion or ingestion into the body (such as transdermal patches, liquid drops);
— apply sonic or electromagnetic energy (such as ultrasonic or iontophoretic devices);
— infusion systems for adding or metering medication into or through systems of artificial tubes, catheters, and/or needles which themselves enter the body.
Kanülenlose Injektionsgeräte zur medizinischen Anwendung - Anforderungen und Prüfverfahren (ISO 21649:2023)
Dieses Dokument ist anwendbar für die Sicherheits-, Leistungs- und Prüfanforderungen für kanülenlose Injektionssysteme (NFIS) zum Einmalgebrauch und zur Wiederverwendung, die für die Anwendung am Menschen in Kliniken und anderen medizinischen Einrichtungen sowie für die persönliche Anwendung durch Patienten vorgesehen sind.
Die Dosierkammer des NFIS ist oft ein Wegwerfartikel und dafür vorgesehen, nach einem einzigen Gebrauch oder einer begrenzten Anzahl von Verwendungen ersetzt zu werden. Sie ist manchmal vom Injektionsmechanismus abnehmbar und wird oft als „Patrone“, „Ampulle“, „Spritze“, „Kapsel“ oder „Scheibe“ bezeichnet. Im Gegensatz dazu kann die Dosierkammer auch eine dauerhafte innere Kammer, die so ausgelegt ist, dass sie über die festgelegte Lebensdauer des Geräts haltbar ist, sowie ein zusätzliches oder mehrere zusätzliche Teile, die das Risiko der Kreuzkontamination ausschließen, enthalten.
Von diesem Dokument ausgeschlossen sind Verfahren zur Medikamentenabgabe, die:
mit einer Durchbohrung eines Teils des Geräts selbst in die oder durch die Haut oder Schleimhäute einher gehen (wie Kanülen, Nadeln, Mikrokanülen, implantierbare Geräte zur langsamen Medikamentenabgabe);
Aerosole, Tröpfchen, Pulver oder andere Rezepturen für die Inhalation, das Einblasen oder die Ablagerung im Nasen- und Mundbereich erzeugen (wie Sprays, Inhalatoren, Vernebler);
Flüssigkeiten, Pulver oder andere Substanzen auf der Oberfläche von Haut oder Schleimhäuten zur passiven Diffusion oder Aufnahme in den Körper ablagern (wie Transkutanpflaster, Flüssigkeitstropfen);
Schall- oder elektromagnetische Energie anwenden (wie Ultraschall- oder Iontophoresegeräte);
Infusionssysteme zur Verabreichung oder Dosierung von Medikamenten in oder durch Systeme künstlicher Schläuche, Katheter und/oder Kanülen sind, die in den Körper eintreten.
Systèmes d'injection sans aiguille pour usage médical - Exigences et méthodes d'essai (ISO 21649:2023)
Le présent document s'applique aux exigences de sécurité, de performance et d'essai relatives aux systèmes d'injection sans aiguille (NFIS), à usage unique et réutilisables, destinés à être utilisés sur des êtres humains dans des cliniques et autres établissements médicaux, ou à l'usage personnel des patients.
La chambre à dose du NFIS est souvent jetable et destinée à être remplacée après un usage unique ou un nombre limité d'utilisations. Elle est parfois distincte du mécanisme d'injection et est souvent appelée «cartouche», «ampoule», «seringue», «capsule» ou «disque». Mais, elle peut également comporter une chambre interne permanente conçue pour être utilisée pendant la durée de vie revendiquée du dispositif, et un ou plusieurs éléments supplémentaires qui éliminent le risque de contamination croisée.
Les méthodes d'administration de médicaments exclues du présent document sont celles qui:
— impliquent la pénétration d'une partie du dispositif proprement dit dans ou à travers la peau ou les muqueuses (comme les aiguilles, les dents, les micro aiguilles, les dispositifs médicaux implantables à libération prolongée);
— génèrent des aérosols, des gouttelettes, des poudres ou d'autres formulations destinées à une inhalation, une insufflation ou à une pulvérisation orale ou intranasale (comme les sprays, les inhalateurs, les nébulisateurs);
— déposent des liquides, des poudres ou d'autres substances à la surface de la peau ou des muqueuses pour une diffusion passive ou ingestion dans le corps (comme les timbres transdermiques, les gouttes liquides);
— appliquent une énergie sonique ou électromagnétique (comme les dispositifs à ultrasons ou iontophorétiques);
— permettent d'ajouter ou de doser le médicament (systèmes de perfusion) dans ou à travers des systèmes ou des tubes artificiels, des cathéters et/ou des aiguilles qui pénètrent eux-mêmes le corps.
Injektorji brez igle za uporabo v medicini - Zahteve in preskusne metode (ISO 21649:2023)
Ta dokument se uporablja za varnost in učinkovitost in zahteve glede preskušanja sistemov za injiciranje brez peres (NFIS) za enkratno in večkratno uporabo, ki so namenjeni za uporabo pri ljudeh v klinikah ali in drugih zdravstvenih okoljih in za osebno uporabo pri bolnikih.
Dozirna posoda sistema NFIS je pogosto namenjena enkratni uporabi in se zamenja po eni uporabi oziroma omejenem številu uporab. Včasih jo je mogoče ločiti od mehanizma za injiciranje in jo pogosto imenujemo »kartuša«, »ampula«, »brizga«, »kapsula« ali »disk«. Dozirna posoda lahko namreč vključuje tudi stalno notranjo posodo, zasnovano za uporabo v celotni življenjski dobi naprave, in dodatni element ali elemente, ki odpravljajo tveganje navzkrižne kontaminacije.
Ta dokument ne zajema metod za dajanje zdravil, ki:
– vključujejo penetracijo dela same naprave v ali skozi kožo ali sluznico (npr. igle, zobci, mikro igle, vsadne naprave za počasno sproščanje zdravila);
– ustvarjajo aerosole, kapljice, praške ali druge oblike za vdihavanje, vpihavanje, nosno ali ustno odmerjanje (npr. pršila, inhalatorji, naprave za ustvarjanje meglice);
– odlagajo tekočine, praške ali druge snovi na površino kože ali sluznice za pasivno difuzijo ali vpijanje v telo (npr. transdermalni obliži, tekočinske kapljice);
– uporabljajo zvočno ali elektromagnetno energijo (npr. ultrazvočne ali iontoforetične naprave);
– uporabljajo infuzijske sisteme za dodajanje ali odmerjanje zdravila v ali prek sistemov umetnih cevk, katetrov in/ali igel, ki vstopajo v telo.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 21649:2023
01-maj-2023
Nadomešča:
SIST EN ISO 21649:2010
Injektorji brez igle za uporabo v medicini - Zahteve in preskusne metode (ISO
21649:2023)
Needle-free injection systems for medical use - Requirements and test methods (ISO
21649:2023)
Kanülenlose Injektionsgeräte zur medizinischen Anwendung - Anforderungen und
Prüfverfahren (ISO 21649:2023)
Systèmes d'injection sans aiguille pour usage médical - Exigences et méthodes d'essai
(ISO 21649:2023)
Ta slovenski standard je istoveten z: EN ISO 21649:2023
ICS:
11.040.20 Transfuzijska, infuzijska in Transfusion, infusion and
injekcijska oprema injection equipment
SIST EN ISO 21649:2023 en,fr,de
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 21649:2023
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SIST EN ISO 21649:2023
EN ISO 21649
EUROPEAN STANDARD
NORME EUROPÉENNE
February 2023
EUROPÄISCHE NORM
ICS 11.040.20 Supersedes EN ISO 21649:2009
English Version
Needle-free injection systems for medical use -
Requirements and test methods (ISO 21649:2023)
Systèmes d'injection sans aiguille pour usage médical - Kanülenlose Injektionsgeräte zur medizinischen
Exigences et méthodes d'essai (ISO 21649:2023) Anwendung - Anforderungen und Prüfverfahren (ISO
21649:2023)
This European Standard was approved by CEN on 23 January 2023.
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, Türkiye 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
© 2023 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 21649:2023 E
worldwide for CEN national Members.
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SIST EN ISO 21649:2023
EN ISO 21649:2023 (E)
Contents Page
European foreword . 3
2
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SIST EN ISO 21649:2023
EN ISO 21649:2023 (E)
European foreword
This document (EN ISO 21649:2023) has been prepared by Technical Committee ISO/TC 84 "Devices
for administration of medicinal products and catheters" in collaboration with Technical Committee
CEN/SS S03 “Syringes” the secretariat of which is held by CCMC.
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 August 2023, and conflicting national standards shall
be withdrawn at the latest by August 2023.
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 21649:2009.
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, Türkiye and the
United Kingdom.
Endorsement notice
The text of ISO 21649:2023 has been approved by CEN as EN ISO 21649:2023 without any modification.
3
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SIST EN ISO 21649:2023
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SIST EN ISO 21649:2023
INTERNATIONAL ISO
STANDARD 21649
Second edition
2023-01
Needle-free injection systems for
medical use — Requirements and test
methods
Systèmes d'injection sans aiguille pour usage médical — Exigences et
méthodes d'essai
Reference number
ISO 21649:2023(E)
© ISO 2023
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SIST EN ISO 21649:2023
ISO 21649:2023(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2023
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 21649:2023
ISO 21649:2023(E)
Contents Page
Foreword .v
Introduction .vii
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Symbols . 4
5 Requirements . 5
5.1 General requirements . 5
5.2 Noise requirements . 6
5.3 Dose accuracy specification requirements . 7
5.4 Usability engineering . . 7
5.5 Risk approach . 7
5.6 Uncertainty of measurements and conformance with specifications . 7
5.7 Performance profile requirements . 8
5.8 Test requirements. 8
5.8.1 NFISs subjected to standard, cool and hot atmospheres and after claimed
lifetime testing (in-use conditions) . 8
5.8.2 Dry heat storage - Preconditioning . 9
5.8.3 Damp heat storage – Preconditioning . 9
5.8.4 Cold storage - Preconditioning . 9
5.8.5 Cyclical testing - Preconditioning . 10
5.8.6 Free fall - Preconditioning . 10
5.8.7 Vibration and shock – Preconditioning . 10
5.8.8 Transport – Preconditioning . 10
5.8.9 NFISs with electrical components subjected to electromagnetic
compatibility (EMC) . 11
5.8.10 Water and dust resistance . 11
5.8.11 Auto-disable feature . 11
6 Test methods .12
6.1 General .12
6.2 Test procedures . 13
6.2.1 General .13
6.2.2 NFISs subjected to standard, cool and hot atmospheres and claimed
lifetime test . 14
6.2.3 NFISs subjected to dry heat storage atmosphere . 16
6.2.4 NFISs subjected to damp-heat storage atmosphere . 16
6.2.5 NFISs subjected to cold storage atmosphere . 17
6.2.6 NFISs subjected to a cyclical atmosphere . 17
6.2.7 NFISs subjected to free fall . 17
6.2.8 NFISs subjected to vibration and shock . . 18
6.2.9 NFISs with electrical components subjected to electromagnetic
compatibility (EMC) testing . 19
6.2.10 Noise testing .20
6.2.11 Water and dust resistance . 21
6.2.12 Auto-disable feature .22
6.3 Test evaluations . 22
6.3.1 Dose accuracy .22
6.3.2 Inspection .23
7 Test report .24
8 Information supplied with the NFIS .24
8.1 General . 24
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SIST EN ISO 21649:2023
ISO 21649:2023(E)
8.2 Marking . 25
8.3 Instructions for use . 25
Annex A (informative) Two-sided tolerance limit factors (k) .26
Annex B (informative) Examples of accuracy limit calculations and random settings.32
Annex C (normative) Instructions for use, marking and age warning .33
Annex D (informative) Example for k factor .35
Bibliography .36
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SIST EN ISO 21649:2023
ISO 21649:2023(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/SS S03, Syringes, in accordance with the Agreement on technical cooperation
between ISO and CEN (Vienna Agreement).
This second edition cancels and replaces the first edition (ISO 21649:2006), which has been technically
revised.
The main changes are as follows:
— changes to update the document to be consistent with the approach and requirements currently in
the ISO 11608 series. This includes:
— use of a risk-based approach to specifications and testing;
— damp heat testing;
— water and dust intrusion;
— transport and lifetime testing.
— changes to address requirements for mass vaccinations such as:
— requirements to reduce the potential for cross contaminations, such as a requirement for a
re-use prevention feature/auto-disable feature for the patient contact portion of a re-usable/
multi-use device;
— changes to address robustness requirements including long-term repetitive use and for use in
harsh environments;
— inclusion of specific requirement and a test method to address potential transfer of pathogens
between patients.
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SIST EN ISO 21649:2023
ISO 21649:2023(E)
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 21649:2023
ISO 21649:2023(E)
Introduction
This document specifies the results of the design effort instead of the physical and construction
requirements used as the basis for device design, so that innovation in achieving the intended purposes
is not unnecessarily restricted.
Standards of this nature intentionally avoid addressing more than the most basic elements regarding
the safety and performance of NFISs in humans. Any intended labelling of such devices indicating
their use to deliver medicinal products into the body or into specified tissue compartments thereof
(e.g. intramuscular, subcutaneous or intradermal), or for the administration of specific pharmaceutical
drugs or vaccines, falls under the authority of national governments or supranational agencies
regulating the manufacture and marketing of medical devices and pharmaceutical products. Despite
certain advantages for intentional interchangeability for dose chambers designed for different NFISs,
as well as the potential risks of inadvertent interchangeability, these standards avoid setting forth
design specifications for the uniform size, shape and interface of such dose chambers.
The sampling plans for inspection selected for this document are intended to verify the design, at a
high confidence level, i.e. the manufacturer's ability to manufacture one “lot” of NFISs, which conforms
to the critical product attributes. The sampling plan does not replace the more general manufacturing
quality systems, including lot release, which appear in standards on quality systems, e.g. ISO 9001or
ISO 13485.
This document assumes 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 according to 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.
Manufacturers are expected to follow a risk-based approach during the design, development, and
manufacture of the NFIS. 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 NFIS (including the medicinal product);
— any substitutions or omissions of requirements, specifications, methods or limits unique to each
specific NFIS (including the medicinal product), when those provided in this document are not
applicable and/or appropriate to the NFIS.
The flexibility provided in this document allows it to be applied to many different device and medicinal
product combinations. However, this makes it difficult to make a general declaration of conformance to
the document. As such, when making any declaration of conformance to this document, such deviations,
exclusions, substitutions, and omissions should be specified and supported by adequate justification in
the design file.
vii
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SIST EN ISO 21649:2023
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SIST EN ISO 21649:2023
INTERNATIONAL STANDARD ISO 21649:2023(E)
Needle-free injection systems for medical use —
Requirements and test methods
1 Scope
This document applies to safety and performance and testing requirements for single-use and multiple-
use Needle-Free Injection Systems (NFISs) intended for human use in clinics and other medical settings
and for personal use by patients.
The dose chamber of the NFIS is often disposable and intended to be replaced after either a single use
or a limited number of uses. It is sometimes separable from the injection mechanism and often termed a
“cartridge”, “ampoule”, “syringe”, “capsule” or “disc”. In contrast, the dose chamber can also incorporate
a permanent internal chamber designed to last through the claimed life of the device, and an additional
member or members which eliminate the risk of cross-contamination.
Excluded from this document are drug delivery methods which:
— involve penetration of a part of the device itself into or through skin or mucous membranes (such as
needles, tines, micro-needles, implantable slow-release drug devices);
— generate aerosols, droplets, powders or other formulations for inhalation, insufflation, intranasal
or oral deposition (such as sprays, inhalers, misters);
— deposit liquids, powders, or other substances on the surface of skin or mucosal surfaces for passive
diffusion or ingestion into the body (such as transdermal patches, liquid drops);
— apply sonic or electromagnetic energy (such as ultrasonic or iontophoretic devices);
— infusion systems for adding or metering medication into or through systems of artificial tubes,
catheters, and/or needles which themselves enter the body.
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 7886-3:2020, Sterile hypodermic syringes for single use — Part 3: Auto-disabled syringes for fixed-dose
immunization
ISO 10993 (all parts), — Biological evaluation of medical devices
ISO 11201, Acoustics — Noise emitted by machinery and equipment — Determination of emission sound
pressure levels at a work station and at other specified positions in an essentially free field over a reflecting
plane with negligible environmental corrections
ISO 11202, Acoustics — Noise emitted by machinery and equipment — Determination of emission sound
pressure levels at a work station and at other specified positions applying approximate environmental
corrections
ISO 11204, Acoustics — Noise emitted by machinery and equipment — Determination of emission sound
pressure levels at a work station and at other specified positions applying accurate environmental
corrections
ISO 14155, Clinical investigation of medical devices for human subjects — Good clinical practice
1
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SIST EN ISO 21649:2023
ISO 21649:2023(E)
ISO 14971:2019, Medical devices — Application of risk management to medical devices
IEC 60068-2-27, Environmental testing — Part 2: Tests. Test Ea and guidance: Shock
IEC 60068-2-31, Environmental testing — Part 2-31: Tests. Test Ec: Rough handling shocks, primarily for
equipment-type specimens
IEC 60068-2-64, Environmental testing — Part 2-64: Tests — Test Fh: Vibration, broad-band random and
guidance
IEC 60529, Degrees of protection provided by enclosures (IP Code)
IEC 60721-3-7:1995+AMD1: 1996, Classification of environmental conditions — Part 3-7: Classification of
groups of environmental parameters and their severities — Portable and non-stationary use
IEC 61000-4-2:2008, Electromagnetic compatibility (EMC) — Part 4-2: Testing and measurement
techniques — Electrostatic discharge immunity test
IEC 61000-4-3:2020, Electromagnetic compatibility (EMC) — Part 4-3: Testing and measurement
techniques — Radiated, radio-frequency, electromagnetic field immunity test
IEC 61672-1, Electroacoustics — Sound level meters — Part 1: Specifications
IEC 62366-1, Medical devices — Part 1: Application of usability engineering to medical devices
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
claimed lifetime
total number of injection strokes that a needle-free injection system (3.8), in normal use with
recommended user maintenance and before manufacturer overhaul or refurbishment of parts, is
expected to administer within its performance profile (3.11) specified by the manufacturer
Note 1 to entry: This number may also be expressed as a period of time (e.g. number of days, weeks, months or
years) at a corresponding frequency of expected usage (e.g. number of injections per day, week, month or year).
3.2
dose chamber
enclosure that contains and is in direct contact with the pharmaceutical product, and from which the
pharmaceutical product is administered to the patient by the needle-free injection system
3.3
dose accuracy
difference between the intended dose and the delivered dose
2
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SIST EN ISO 21649:2023
ISO 21649:2023(E)
3.4
injection mechanism
components of the needle-free injection system (3.8) which are designated to harness, store, regulate,
control and transfer to the dose chamber (3.2) and/or its contained medicinal product the e
...
SLOVENSKI STANDARD
oSIST prEN ISO 21649:2022
01-april-2022
Injektorji brez igle za uporabo v medicini - Zahteve in preskusne metode (ISO/DIS
21649:2022)
Needle-free injection systems for medical use - Requirements and test methods
(ISO/DIS 21649:2022)
Kanülenlose Injektionsgeräte zur medizinischen Anwendung – Anforderungen und
Prüfverfahren (ISO/DIS 21649:2022)
Systèmes d'injection sans aiguille pour usage médical - Exigences et méthodes d'essai
(ISO/DIS 21649:2022)
Ta slovenski standard je istoveten z: prEN ISO 21649
ICS:
11.040.20 Transfuzijska, infuzijska in Transfusion, infusion and
injekcijska oprema injection equipment
oSIST prEN ISO 21649:2022 en,fr,de
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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oSIST prEN ISO 21649:2022
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oSIST prEN ISO 21649:2022
DRAFT INTERNATIONAL STANDARD
ISO/DIS 21649
ISO/TC 84 Secretariat: DS
Voting begins on: Voting terminates on:
2022-02-14 2022-05-09
Needle-free injection systems for medical use —
Requirements and test methods
ICS: 11.040.20
This document is circulated as received from the committee secretariat.
THIS DOCUMENT IS A DRAFT CIRCULATED
FOR COMMENT AND APPROVAL. IT IS
ISO/CEN PARALLEL PROCESSING
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
IN ADDITION TO THEIR EVALUATION AS
BEING ACCEPTABLE FOR INDUSTRIAL,
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
STANDARDS MAY ON OCCASION HAVE TO
BE CONSIDERED IN THE LIGHT OF THEIR
POTENTIAL TO BECOME STANDARDS TO
WHICH REFERENCE MAY BE MADE IN
Reference number
NATIONAL REGULATIONS.
ISO/DIS 21649:2022(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 2022
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oSIST prEN ISO 21649:2022
ISO/DIS 21649:2022(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
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oSIST prEN ISO 21649:2022
ISO/DIS 21649:2022(E)
Contents Page
Foreword .v
Introduction . vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Symbols and abbreviated terms.4
5 Requirements . 5
5.1 General requirements . 5
5.2 Noise requirements . 6
5.3 Dose accuracy specification requirements . 7
5.4 Usability engineering . . 7
5.5 Risk approach . 7
5.6 Uncertainty of measurements and conformance with specifications . 8
5.7 Performance profile requirements . 8
5.8 Test requirements. 9
5.8.1 NFISs subjected to standard, cool and hot atmospheres and after claimed
lifetime testing (in-use conditions) . 9
5.8.2 Dry heat storage - Preconditioning . 9
5.8.3 Damp heat storage – Preconditioning . 9
5.8.4 Cold storage - Preconditioning . 10
5.8.5 Cyclical testing - Preconditioning . 10
5.8.6 Free fall - Preconditioning . 10
5.8.7 Vibration and shock - Preconditioning . 10
5.8.8 Transport – Preconditioning . 11
5.8.9 NFISs with electrical components subjected to electromagnetic
compatibility (EMC) . 11
5.8.10 Water and dust resistance .12
5.8.11 Auto-disable feature .12
6 Test methods .12
6.1 General .12
6.2 Test procedures . 13
6.2.1 General .13
6.2.2 NFISs subjected to standard, cool and hot atmospheres and claimed
lifetime test . 14
6.2.3 NFISs subjected to dry heat storage atmosphere . 16
6.2.4 NFISs subjected to damp-heat storage atmosphere . 16
6.2.5 NFISs subjected to cold storage atmosphere . 17
6.2.6 NFISs subjected to a cyclical atmosphere . 17
6.2.7 NFISs subjected to free fall . 18
6.2.8 NFISs subjected to vibration and shock . . 19
6.2.9 NFISs with electrical components subjected to electromagnetic
compatibility (EMC) testing . 20
6.2.10 Noise testing .20
6.2.11 Water and dust resistance . 22
6.2.12 Auto-disable feature . 22
6.3 Test evaluations . 23
6.3.1 Dose accuracy .23
6.3.2 Inspection . 24
7 Test report .25
8 Information supplied with the NFIS .25
8.1 General . 25
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8.2 Marking . 25
8.3 Instructions for use . 26
Annex A (informative) Two-sided tolerance limit factors (k) .27
Annex B (informative) Examples of accuracy limit calculations and random settings.33
Annex C (normative) Instructions for use, marking and age warning symbol .34
Annex D (informative) Example for k factor .37
Bibliography .38
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oSIST prEN ISO 21649:2022
ISO/DIS 21649:2022(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.
This second edition cancels and replaces the first edition (ISO 21649:2006), which has been technically
revised.
The main changes compared to the previous edition are as follows:
— Changes to update the document to be consistent with the approach and requirements currently in
the updated ISO 11608 series. This includes:
— Use of a risk-based approach to specifications and testing;
— Damp heat testing;
— Water and dust intrusion;
— Transport and lifetime testing.
— Changes to address requirements for mass vaccinations such as :
— Requirements to reduce the potential for cross contaminations, such as a requirement for a
re-use prevention feature/auto-disable feature for the patient contact portion of a re-usable/
multi-use device;
— Address robustness requirements of the WHO PQ specification into the document, including
long-term repetitive use and for use in harsh environments;
— Include specific requirement and a test method to address potential transfer of pathogens
between patients.
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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oSIST prEN ISO 21649:2022
ISO/DIS 21649:2022(E)
Introduction
This document applies to needle-free injection systems (NFISs) primarily intended to administer
medicinal products to humans. Because of the anticipated variation in the designs of such a broad
array of devices, this document is promulgated more as a “horizontal” rather than a “vertical” one.
Thus, it will tend to specify the results of the design effort instead of the physical and construction
requirements used as the basis for device design, so that innovation in achieving the intended purposes
is not unnecessarily restricted.
Standards of this nature intentionally avoid addressing more than the most basic elements regarding
the safety and performance of NFISs in humans. Any intended labelling of such devices indicating their
use to deliver medicinal products into the body or into specified tissue compartments thereof (e.g.
intramuscular, subcutaneous or intradermal), or for the administration of specific pharmaceutical drugs
or vaccines, shall fall under the authority of national governments or supranational agencies regulating
the manufacture and marketing of medical devices and pharmaceutical products. Such standards are
expected to be supplemented by additional requirements and may occasionally be superseded by such
regulatory authorities. Despite certain advantages for intentional interchangeability for dose chambers
designed for different NFISs, as well as the potential risks of inadvertent interchangeability, these
standards avoid setting forth design specifications for the uniform size, shape and interface of such
dose chambers. This issue is left for future initiatives to build upon the standards promulgated herein.
The sampling plans for inspection selected for this document are intended to verify the design, at a
high confidence level, i.e. the manufacturer's ability to manufacture one “lot” of NFISs, which conforms
to the critical product attributes. The sampling plan does not replace the more general manufacturing
quality systems, including lot release, which appear in standards on quality systems, e.g. the ISO 9000
series or ISO 13485.
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 shall be addressed individually according to 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.
Manufacturers are expected to follow a risk-based approach during the design, development, and
manufacture of the NFIS. Given that each product may 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 NFIS (including the medicinal product); and
— any substitutions or omissions of requirements, specifications, methods or limits unique to each
specific NFIS (including the medicinal product), when those provided in this document are not
applicable and/or appropriate to the NFIS.
The flexibility provided in this document allows it to be applied to many different device and medicinal
product combinations. However, this makes it difficult to make a general declaration of conformance to
the document. As such, when making any declaration of conformance to this document, such deviations,
exclusions, substitutions, and omissions must be specified and supported by adequate justification in
the design file.
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oSIST prEN ISO 21649:2022
DRAFT INTERNATIONAL STANDARD ISO/DIS 21649:2022(E)
Needle-free injection systems for medical use —
Requirements and test methods
1 Scope
This document applies to safety and performance and testing requirements for single-use and multiple-
use Needle-Free Injection Systems (NFISs) intended for human use in clinics and other medical settings
and for personal use by patients.
The dose chamber of the NFIS is often disposable and intended to be replaced after either a single
use or a limited number of uses. It is sometimes separable from the injection mechanism and often
termed a “cartridge”, “ampoule”, “syringe”, “capsule” or “disc”. In contrast, the dose chamber may also
incorporate a permanent internal chamber designed to last through the claimed life of the device, and
an additional member or members which eliminate the risk of cross-contamination.
Excluded from this document are drug delivery methods which:
— involve penetration of a part of the device itself into or through skin or mucous membranes (such as
needles, tines, micro-needles, implantable slow-release drug devices);
— generate aerosols, droplets, powders or other formulations for inhalation, insufflation, intranasal
or oral deposition (such as sprays, inhalers, misters);
— deposit liquids, powders, or other substances on the surface of skin or mucosal surfaces for passive
diffusion or ingestion into the body (such as transdermal patches, liquid drops);
— apply sonic or electromagnetic energy (such as ultrasonic or iontophoretic devices);
— infusion systems for adding or metering medication into or through systems of artificial tubes,
catheters, and/or needles which themselves enter the body.
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 7886-3:2020, Sterile hypodermic syringes for single use — Part 3: Auto-disabled syringes for fixed-dose
immunization
ISO 10993 (all parts), — Biological evaluation of medical devices
ISO 11201, Acoustics — Noise emitted by machinery and equipment — Determination of emission sound
pressure levels at a work station and at other specified positions in an essentially free field over a reflecting
plane with negligible environmental corrections
ISO 11202, Acoustics — Noise emitted by machinery and equipment — Determination of emission sound
pressure levels at a work station and at other specified positions applying approximate environmental
corrections
ISO 11204, Acoustics — Noise emitted by machinery and equipment — Determination of emission sound
pressure levels at a work station and at other specified positions applying accurate environmental
corrections
ISO 14155-1, Clinical investigation of medical devices for human subjects — Good clinical practice
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ISO 14253-1, Geometrical product specifications (GPS) — Inspection by measurement of workpieces and
measuring equipment — Part 1: Decision rules for verifying conformity or nonconformity with specifications
IEC 60068-2-27, Environmental testing — Part 2: Tests. Test Ea and guidance: Shock
IEC 60068-2-30:2005, Environmental testing — Part 2-30: Tests. Test Db and guidance: Damp heat, cyclic
(12 h + 12 h cycle)
IEC 60068-2-31, Environmental testing — Part 2-31: Tests. Test Ec: Rough handling shocks, primarily for
equipment-type specimens
IEC 60068-2-64, Environmental testing — Part 2-64: Tests — Test Fh: Vibration, broad-band random and
guidance
IEC 60529, Degrees of protection provided by enclosures (IP Code)
I EC 6 0721-3-7:19 95+A M D1: 19 96 , CSV (Consolidated version), Classification of environmental conditions —
Part 3-7: Classification of groups of environmental parameters and their severities — Portable and non-
stationary use
IEC 61000-4-2:2008, Electromagnetic compatibility (EMC) — Part 4-2: Testing and measurement
techniques — Electrostatic discharge immunity test
IEC 61000-4-3:2020, Electromagnetic compatibility (EMC) — Part 4-3: Testing and measurement
techniques — Radiated, radio-frequency, electromagnetic field immunity test
IEC 61672-1, Electroacoustics — Sound level meters — Part 1: Specifications
IEC 62366-1, Medical devices — Part 1: Application of usability engineering to medical devices
ISO/IEC Guide 98-3, Uncertainty of measurement — Part 3: Guide to the expression of uncertainty in
measurement (GUM: 1995)
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological 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
claimed lifetime
total number of injection strokes that a needle-free injection system (3.9), in normal use with
recommended user maintenance and before manufacturer overhaul or refurbishment of parts, is
expected to administer within its performance profile (3.12) specified by the manufacturer
Note 1 to entry: This number may also be expressed as a period of time (e.g. number of days, weeks, months or
years) at a corresponding frequency of expected usage (e.g. number of injections per day, week, month or year).
3.2
dose chamber
enclosure which contains and is in direct contact with the pharmaceutical product, and from which the
pharmaceutical product is administered to the patient by the NFIS
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oSIST prEN ISO 21649:2022
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3.3
dose indicator
component of a needle-free injection system (3.9) showing the intended dose (3.6) to be delivered
Note 1 to entry: Depending on the device design, such indication may or may not be apparent before the dose
chamber (3.2) is filled.
3.4
dose accuracy
difference between the intended dose and the delivered dose
3.5
injection mechanism
components of the needle-free injection system (3.9) which are designated to harness, store, regulate,
control and transfer to the dose chamber (3.2) and/or its contained medicinal product the energies
required for the injection to occur, including means to prevent release of such energies, such as a "safety
latch"
Note 1 to entry: This term is not used to refer to separate accessories which transfer energy into the NFIS but
which are separated from the NFIS at the time of the injection (such as a separate spring-cocking mechanism,
a gas pressurizing tank, a foot pump or other separate device using electricity, muscle power or other energy
source).
3.6
intended dose
amount (volume or mass) of medicinal product intended to be expelled at one time
3.7
maximum dose
volumes, masses or number of units representing the largest quantities, which the manufacturer
designates the needle-free injection system (3.9) is capable of expelling by one injection
3.8
minimum dose
volumes, masses or number of units representing the smallest quantities, which the manufacturer
designates the needle-free injection system (3.9) is capable of expelling by one injection
3.9
needle-free injection system
NFIS
injector and its components and accessories that administer a medicinal product to a patient by using
mechanical motion (such as movement of a piston or flow of a gas, but not to exclude other means) to
impart kinetic energy to the medicinal product, without any part of the system penetrating the skin or
mucous membranes
Note 1 to entry: Such components and accessories may include:
— disposable or re-usable dose chambers (3.2);
— separable mechanisms that obtain, transfer, convert, or store energy (using hydraulic, pneumatic, mechanical,
electrical, chemical or other means);
— filling devices to hold dose chambers (3.2) and feed them into the injector or vessels to capture and dispose of
used containers;
— instructions and educational materials for end-users.
3.10
nozzle
component of an injector through which the medicinal product is expelled
Note 1 to entry: The nozzle may or may not, depending on the device design, make physical contact with the skin
or other membranes of the patient.
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3.11
orifice
hole at the end of the nozzle (3.10), through which the medicinal product is expelled
3.12
performance profile
manufacturer-specified set of measurable and quantitative values and tolerance intervals which
describes the proper functioning of a needle-free injection system (3.9)
3.13
reservoir
intermediate enclosure that holds
...
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