EN ISO 27427:2023
(Main)Anaesthetic and respiratory equipment - Nebulizing systems and components (ISO 27427:2023)
Anaesthetic and respiratory equipment - Nebulizing systems and components (ISO 27427:2023)
This document specifies requirements for the safety and performance testing of general-purpose nebulizing systems intended for continuous or breath-actuated delivery of liquids, in aerosol form, to humans through the respiratory system.
This document includes gas-powered nebulizers (which can be powered by, e.g., compressors, pipeline systems, cylinders, etc.) and electrically powered nebulizers [e.g. spinning disc, ultrasonic, vibrating mesh (active and passive), and capillary devices] or manually powered nebulizers. This document does not specify the electrical requirements of electrically powered nebulizers.
This document does not specify the minimum performance of nebulizing systems.
This document does not apply to:
a) devices intended for nasal deposition;
b) devices intended solely to provide humidification or hydration by providing water in aerosol form.
NOTE 1 ISO 80601-2-74 and ISO 20789 cover these devices.
c) drug-specific nebulizers or their components (e.g. metered dose inhalers, metered liquid inhalers, dry powder inhalers).
NOTE 2 ISO 20072 covers these devices.
NOTE 3 See Annex A for rationale.
Atemtherapiegeräte - Verneblersysteme und deren Bauteile (ISO 27427:2023)
Dieses Dokument legt Anforderungen für die Prüfung der Sicherheit und Leistung von Mehrzweck-Verneblersystemen fest, die für die kontinuierliche oder atmungsaktivierte Ausgabe von Flüssigkeiten in Form von Aerosolen an Menschen durch das Atmungssystem vorgesehen sind.
Dieses Dokument schließt gasbetriebene Vernebler (die z. B. mit Kompressoren, Rohrleitungssystemen, Gasflaschen usw. betrieben werden können) und elektrisch betriebene Vernebler [z. B. Drehscheibe, Ultraschall, vibrierende Mesh-Vernebler (aktiv und passiv) und Kapillargeräte] oder von Hand betriebene Vernebler ein. Dieses Dokument legt keine elektrischen Anforderungen an elektrisch betriebene Vernebler fest.
Dieses Dokument legt keine Mindestangaben für die Leistung von Verneblersystemen fest.
Dieses Dokument ist nicht anwendbar für:
a) Geräte, die für die nasale Ablagerung vorgesehen sind,
b) Geräte, die ausschließlich für die Erzeugung von Feuchte oder für die Hydration durch Bereitstellung von Wasser in Form von Aerosolen vorgesehen sind.
ANMERKUNG 1 Diese Geräte werden von ISO 80601 2 74 und ISO 20789 abgedeckt.
c) Vernebler für bestimmte Medikamente oder ihre Bauteile (z. B. Inhaliergeräte mit Dosierungen nach dem metrischen System, Flüssigkeits-Dosierinhaliergeräte, Trockenpulver-Inhaliergeräte).
ANMERKUNG 2 Diese Geräte werden von ISO 20072 abgedeckt.
ANMERKUNG 3 Siehe Anhang A für die Begründung.
Matériel d'anesthésie et de réanimation respiratoire - Systèmes de nébulisation et leurs composants (ISO 27427:2023)
Le présent document spécifie les exigences relatives à la sécurité, aux performances et aux essais des systèmes de nébulisation à usage général destinés à l’administration continue ou déclenchée par la respiration, sous forme d’un aérosol, de liquides aux personnes, via le système respiratoire.
Le présent document inclut les nébuliseurs pneumatiques qui peuvent être alimentés, par exemple par compresseurs, par réseau de gaz médicaux, par bouteilles, etc. ainsi que les nébuliseurs électriques [par exemple les dispositifs à disque rotatif, ultrasoniques, à tamis vibrant (actif et passif) et à capillaire] ou les nébuliseurs manuels. Le présent document ne spécifie pas les exigences électriques pour les nébuliseurs électriques.
Le présent document ne spécifie pas de performance minimale pour les systèmes de nébulisation.
Le présent document ne s’applique pas aux:
a) dispositifs pour traitement nasal;
b) dispositifs uniquement destinés à assurer une humidification ou une hydratation en fournissant de l’eau sous forme d’aérosol.
NOTE 1 L’ISO 80601-2-74 et l’ISO 20789 couvrent ces dispositifs.
c) nébuliseurs spécifiques à des médicaments ou à leurs composants (par exemple aérosols doseurs, aérosols doseurs de liquide, inhalateurs à poudre sèche).
NOTE 2 L’ISO 20072 couvre ces dispositifs.
NOTE 3 Voir l’Annexe A pour les justifications.
Anestezijska in dihalna oprema - Razprševalni sistemi in sestavni deli (ISO 27427:2023)
Ta dokument določa zahteve glede varnosti in preskušanje učinkovitosti razprševalnih sistemov za splošno uporabo, ki so namenjeni stalnemu ali z vdihavanjem aktiviranemu dovajanju tekočin v aerosolni obliki prek dihalnega sistema.
Ta dokument vključuje nebulatorje s potisnim plinom, ki se lahko napajajo npr. prek kompresorjev, cevovodov, jeklenk itd., ter električne nebulatorje (npr. z vrtečim diskom, ultrazvočni, z vibrirajočo mrežico (aktivno ali pasivno) in kapilarne naprave) ali ročne nebulatorje. Ta dokument ne določa električnih zahtev za električne nebulatorje.
Ta dokument ne določa minimalne učinkovitosti razprševalnih sistemov.
Ta dokument se ne uporablja za:
a) pripomočke, namenjene za nosno odmerjanje;
b) pripomočke, ki so namenjeni izključno zagotavljanju vlaženja ali hidracije z zagotavljanjem vode v obliki aerosola.
OPOMBA 1: Te pripomočke obravnavata standarda ISO 80601-2-74 in ISO 20789.
c) nebulatorje za določena zdravila ali njihove sestavne dele (npr. inhalatorji z odmerjenimi odmerki, inhalatorji z odmerjenimi tekočinami, inhalatorji s suhim prahom).
OPOMBA 2: Te pripomočke obravnava standard ISO 20072.
OPOMBA 3: Za osnovno utemeljitev glej dodatek A.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
01-oktober-2023
Nadomešča:
SIST EN ISO 27427:2019
Anestezijska in dihalna oprema - Razprševalni sistemi in sestavni deli (ISO
27427:2023)
Anaesthetic and respiratory equipment - Nebulizing systems and components (ISO
27427:2023)
Atemtherapiegeräte - Verneblersysteme und deren Bauteile (ISO 27427:2023)
Matériel d'anesthésie et de réanimation respiratoire - Systèmes de nébulisation et leurs
composants (ISO 27427:2023)
Ta slovenski standard je istoveten z: EN ISO 27427:2023
ICS:
11.040.10 Anestezijska, respiratorna in Anaesthetic, respiratory and
reanimacijska oprema reanimation equipment
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
EN ISO 27427
EUROPEAN STANDARD
NORME EUROPÉENNE
July 2023
EUROPÄISCHE NORM
ICS 11.040.10 Supersedes EN ISO 27427:2019
English Version
Anaesthetic and respiratory equipment - Nebulizing
systems and components (ISO 27427:2023)
Matériel d'anesthésie et de réanimation respiratoire - Atemtherapiegeräte - Verneblersysteme und deren
Systèmes de nébulisation et leurs composants (ISO Bauteile (ISO 27427:2023)
27427:2023)
This European Standard was approved by CEN on 3 March 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 27427:2023 E
worldwide for CEN national Members.
Contents Page
European foreword . 3
European foreword
This document (EN ISO 27427:2023) has been prepared by Technical Committee ISO/TC 121
"Anaesthetic and respiratory equipment" in collaboration with Technical Committee CEN/TC 215
“Respiratory and anaesthetic equipment” the secretariat of which is held by BSI.
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 January 2024, and conflicting national standards shall
be withdrawn at the latest by January 2024.
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 27427:2019.
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 27427:2023 has been approved by CEN as EN ISO 27427:2023 without any modification.
INTERNATIONAL ISO
STANDARD 27427
Fourth edition
2023-07
Anaesthetic and respiratory
equipment — Nebulizing systems and
components
Matériel d'anesthésie et de réanimation respiratoire — Systèmes de
nébulisation et leurs composants
Reference number
ISO 27427:2023(E)
ISO 27427:2023(E)
© 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
ii
ISO 27427:2023(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 General requirements and requirements for test . 3
4.1 General . 3
4.2 Test methods and alternatives . 4
4.2.1 Test methods for aerosol output, aerosol output rate, and particle sizing . 4
4.2.2 Alternative test methods . 4
4.2.3 Calibration and setup . 4
5 Materials . 4
5.1 General . 4
5.2 Biocompatibility . 4
6 Design Requirements.4
6.1 General . 4
6.2 Inlet and outlet ports . 5
6.2.1 Inlet ports . 5
6.2.2 Outlet port . 7
6.3 Flow-direction-sensitive components . 7
6.4 Cleaning and disinfection or sterilization . 7
6.5 Rotary controls . 7
7 Requirement for nebulizing systems and components supplied sterile .7
8 Packaging. 7
9 Information supplied by the manufacturer . 7
9.1 General . 7
9.2 Marking . 7
9.2.1 General . 7
9.2.2 Marking of the nebulizing system: . . 8
9.2.3 Marking on the packaging or individual pack . 8
9.3 Instructions for use . 9
9.3.1 General information . 9
9.3.2 Performance disclosures. 9
9.3.3 Driving gas supply information . 10
Annex A (informative) Rationale .11
Annex B (informative) Diameters of respirable fraction particles .15
Annex C (normative) Test methods for aerosol output and aerosol output rate .16
Annex D (normative) Test methods for particle sizing .19
Annex E (informative) Hazard identification for risk assessment .27
Annex F (informative) Classification of general-purpose nebulizers .30
Bibliography .32
iii
ISO 27427:2023(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 121, Anaesthetic and respiratory
equipment, Subcommittee SC 2, Airways and related equipment, in collaboration with the European
Committee for Standardization (CEN) Technical Committee CEN/TC 215, Respiratory and anaesthetic
equipment, in accordance with the Agreement on technical cooperation between ISO and CEN (Vienna
Agreement).
This fourth edition cancels and replaces the third edition (ISO 27427:2013), which has been technically
revised.
The main changes are as follows:
— Alignment with the general standard for airway devices, ISO 18190;
— updating of references.
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.
iv
ISO 27427:2023(E)
Introduction
Nebulizers are widely used to deliver drugs and vaccines in an aerosol form to humans through the
respiratory system. Nebulizers are also used for diagnostic purposes using radioisotopes for lung
challenge tests. These drugs can be in the form of a solution, suspension or emulsion. Aerosol inhalation
is the preferred route of administration for some drugs. Some drugs are intended for treatment of
systemic diseases and other drugs are intended to treat respiratory diseases. To achieve the intended
treatment, aerosol particles are deposited in specific parts of the respiratory tract. Different size
particles tend to deposit in different parts of the respiratory system; therefore, the performance
profile and the intended use of the nebulizer is specified by the manufacturer and in the accompanying
documentation.
This document was developed to cover “general purpose” nebulizers and is based on adult test
parameters which are likely to be different than stated when testing for paediatric or infant patient
populations. It was specifically written to ensure that the results of the various tests declared by the
manufacturer are meaningful to the users and buyers of nebulizers.
The objectives of this document are to ensure
— suitability of the nebulizers for the intended use as disclosed by the manufacturer;
— safety, particularly for electrically powered nebulizers;
— compatibility between the materials of the components and the dispensed liquid; and
— biocompatibility of the materials of the components that come into contact with the human body.
This document is written following the format of ISO 18190, which is the general standard for airways
and related equipment. The requirements in this device-specific standard take precedence over any
conflicting requirements in ISO 18190.
v
INTERNATIONAL STANDARD ISO 27427:2023(E)
Anaesthetic and respiratory equipment — Nebulizing
systems and components
1 Scope
This document specifies requirements for the safety and performance testing of general-purpose
nebulizing systems intended for continuous or breath-actuated delivery of liquids, in aerosol form, to
humans through the respiratory system.
This document includes gas-powered nebulizers (which can be powered by, e.g., compressors, pipeline
systems, cylinders, etc.) and electrically powered nebulizers [e.g. spinning disc, ultrasonic, vibrating
mesh (active and passive), and capillary devices] or manually powered nebulizers. This document does
not specify the electrical requirements of electrically powered nebulizers.
This document does not specify the minimum performance of nebulizing systems.
This document does not apply to:
a) devices intended for nasal deposition;
b) devices intended solely to provide humidification or hydration by providing water in aerosol form.
NOTE 1 ISO 80601-2-74 and ISO 20789 cover these devices.
c) drug-specific nebulizers or their components (e.g. metered dose inhalers, metered liquid inhalers,
dry powder inhalers).
NOTE 2 ISO 20072 covers these devices.
NOTE 3 See Annex A for rationale.
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 5356-1, Anaesthetic and respiratory equipment — Conical connectors — Part 1: Cones and sockets
ISO 7396-1, Medical gas pipeline systems — Part 1: Pipeline systems for compressed medical gases and
vacuum
ISO 18190:2016, Anaesthetic and respiratory equipment — General requirements for airways and related
equipment
ISO 18562-1, Biocompatibility evaluation of breathing gas pathways in healthcare applications — Part 1:
Evaluation and testing within a risk management process
ISO 23328-1, Breathing system filters for anaesthetic and respiratory use — Part 1: Salt test method to
assess filtration performance
ISO 80369-2, Small-bore connectors for liquids and gases in healthcare applications — Part 2: Connectors
for breathing systems and driving gases applications
ISO 27427:2023(E)
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
aerosol
suspension of particles in gas
Note 1 to entry: Particles can be liquid or solid.
Note 2 to entry: The gas can be the driving gas or ambient air.
3.2
aerosol output
mass or volume of aerosol emitted by the nebulizing system at the aerosol outlet port for the given fill
volume
3.3
aerosol outlet port
outlet of the nebulizing system through which the aerosol is emitted
3.4
aerosol output rate
mass or volume of aerosol emitted by the nebulizing system per unit of time
3.5
breath-actuated nebulizer
nebulizer triggered by a respiratory parameter
Note 1 to entry: Examples of this classification are found in Annex F.
3.6
continuous nebulizer
nebulizer in which aerosol is delivered continuously over multiple inhalation/exhalation breathing
cycles or over long periods
3.7
electrically-powered nebulizer
nebulizer that operates by means of electrical power
Note 1 to entry: Electrically powered nebulizers include ultrasonic, vibrating mesh and capillary-type devices.
3.8
gas-powered nebulizer
nebulizer in which the aerosol is generated by compressed gas
3.9
liquid container
part of the nebulizer that contains the liquid for nebulization
3.10
manually powered nebulizer
nebulizer that operates by means of human power
ISO 27427:2023(E)
3.11
mass median aerodynamic diameter
MMAD
particle size at which 50 % of the mass of the active component are contained in droplets of smaller or
equal aerodynamic diameter
3.12
maximum fill volume
maximum volume of liquid, expressed in millilitres, in the liquid container when the nebulizer is filled to
its maximum filling level
3.13
nebulizer
device that converts a liquid to an aerosol
Note 1 to entry: A nebulizer is also known as an aerosol generator.
3.14
nebulizing system
parts, including the nebulizer and all other components, up to and including the aerosol outlet port,
required to make the aerosol available for inhalation
Note 1 to entry: Airway devices (e.g. masks, tracheal and tracheostomy tubes, supralaryngeal airways) and
breathing systems are not part of the nebulizing system.
3.15
percentage of fill volume emitted
aerosol output expressed as a percentage of the fill volume recommended by the manufacturer that is
emitted by the nebulizer
3.16
residual volume
estimated volume of liquid remaining in the nebulizing system when the nebulizer stops generating an
aerosol
3.17
respirable fraction
fraction of aerosol droplets below 5 μm in diameter expressed as a percentage of the total aerosol
distribution
Note 1 to entry: The respirable fraction can be converted to a percentage (%) by multiplying by 100.
3.18
test solution
aqueous solution used for the type-tests to characterize aerosol output, aerosol output rate, and particle
sizing
Note 1 to entry: See 4.2.1.2, 9.3.2 j) and k), Annex C, and Annex D.
3.19
test substance
active ingredient contained in the test solution
4 General requirements and requirements for test
4.1 General
ISO 18190:2016, Clause 4 applies.
NOTE See Annex E for a list of hazards than can be used as guidance in risk assessment.
ISO 27427:2023(E)
4.2 Test methods and alternatives
4.2.1 Test methods for aerosol output, aerosol output rate, and particle sizing
The type-test methods for aerosol output, aerosol output rate, and particle sizing in air are specified in
Annexes C and D.
4.2.1.1 All type-test methods shall be performed on at least three representative devices of the same
type.
Check conformance by inspection of the technical file/documentation.
4.2.1.2 The type-test methods shall use a test solution of albuterol 0,1 % (mass/mass or volume/
volume (m/m or V/V)) concentration in 0,9 % sodium chloride solution or 2,5 % (m/m OR V/V) sodium
fluoride in distilled water with the provision that its use is declared in the accompanying documents.
See 9.3.2 j).
Check conformance by inspection of the technical file/documentation and the accompanying documents.
4.2.2 Alternative test methods
The manufacturer can use type-test methods for aerosol output, aerosol output rate, and particle sizing
different from those specified in Annexes C and D, provided that any:
a) alternative test methods are validated against the test methods in Annexes C and D to demonstrate
equivalency and that
b) the demonstration of equivalency is included in the technical documentation of the manufacturer.
Check conformance by inspection of the technical file/documentation.
4.2.3 Calibration and setup
To establish confidence in the test method, it is recommended that mass balance procedures be
incorporated during initial determinations. It is also recommended that occasional checks for system
leaks and overall efficiency of analysis be performed.
5 Materials
5.1 General
ISO 18190:2016, Clause 5 applies.
5.2 Biocompatibility
Materials used to manufacture nebulizing systems shall be evaluated for biocompatibility. The
breathing gas pathways shall be evaluated for biocompatibility as specified in ISO 18562-1 and tested
as appropriate.
Check conformance by inspection of the technical file/documentation.
6 Design Requirements
6.1 General
ISO 18190:2016, Clause 6 applies.
ISO 27427:2023(E)
6.2 Inlet and outlet ports
6.2.1 Inlet ports
The driving gas inlet port of a nebulizing system shall be compatible with the gas delivery system to
which it is intended to be connected and shall be one of the following (see Figure 1):
a) a socket R2 connector conforming to ISO 80369-2; or
b) permanently attached (i.e. not removable without the use of a tool).
Check conformance by inspection of the technical file/documentation.
ISO 27427:2023(E)
Key
1 terminal unit conforming to ISO 9170-1
2 probe, conforming to ISO 9170-1
3 flow meter conforming to ISO 15002
4 body of 9/16 UNF DISS connector conforming to CGA V-5-2008, or body of 3/4 UNF DISS connector conforming
to CGA V-5-2008 or a nipple conforming to ISO 17256
5 9/16-18UNF-2A-RH socket connector conforming to CGA V-5-2008 or 3/4-16UNF-2A-RH socket connector
conforming to CGA V-5-2008 or a funnel conforming to ISO 17256
6 permanently attached
7 nebulizer
8 cone R2 connector conforming to ISO 80369-2
9 socket R2 connector conforming to ISO 80369-2
10 pressure regulator conforming to ISO 10524-1
11 compressor conforming to this document (ISO 27427)
12 aerosol mask vented
13 breathing tube conforming to ISO 5367
14 connector conforming to ISO 5356-1
15 T-piece with connectors conforming to ISO 5356-1
16 mouthpiece
17 tracheal tube conforming to ISO 5361
18 HME conforming to ISO 9360-1
a
To the patient.
Figure 1 — Examples of inlet and outlet ports for nebulizer systems
ISO 27427:2023(E)
6.2.2 Outlet port
6.2.2.1 If intended for use in breathing systems, the aerosol outlet port shall conform to ISO 5356-1.
Check conformance by inspection of the technical file/documentation.
6.2.2.2 If not intended for use in breathing systems, the aerosol outlet port shall not misconnect with
connectors conforming to ISO 5356-1, or ISO 80369-1.
Check conformance by inspection of the technical file/documentation.
6.3 Flow-direction-sensitive components
Any flow-direction-sensitive, operator-detachable component shall be designed so that it cannot be
fitted in such a way as to present a hazard to the patient.
Check conformance by functional testing.
6.4 Cleaning and disinfection or sterilization
Nebulizing systems and components intended for reuse shall be constructed so as to enable dismantling
for cleaning and disinfection or sterilization.
NOTE See also ISO 17664 -1.
Check conformance by testing the disassembly/assembly procedure according to the manufacturer's
instructions.
6.5 Rotary controls
The manufacturer should ensure consistency regarding the direction of movement of rotary controls of
the device.
7 Requirement for nebulizing systems and components supplied sterile
ISO 18190:2016, Clause 7 applies.
8 Packaging
ISO 18190:2016, Clause 8 applies.
9 Information supplied by the manufacturer
9.1 General
ISO 18190:2016, Clause 9 applies.
9.2 Marking
9.2.1 General
9.2.1.1 Marking shall be durable following exposure to typical substances in contact during its
intended use and remain legible for the intended duration of use.
ISO 27427:2023(E)
NOTE The durability requirements for markings that are exposed to saliva or mucus over a prolonged period
differ from the durability requirements for markings that are not exposed to prolonged exposure. Also, certain
markings might not be exposed to saliva or mucus but can come in intermittent contact with the skin oil.
Check compliance by exposing the appropriate marking areas of the product to the applicable substances
listed for a cumulative duration of time equivalent to the expected exposure duration in use:
— Drugs or chemicals which will contact the product in use and are listed in the Instructions for Use
(IFU).
— If applicable, artificial saliva
— If applicable, artificial mucus
— If applicable, artificial skin oil
9.2.1.2 Marking shall be legible after cleaning to the manufacturer’s instructions.
9.2.2 Marking of the nebulizing system:
The following shall be marked either on the nebulizer or its components as applicable:
a) an arrow showing the direction of gas flow on all operator-detachable flow-direction-sensitive
components, breathing attachments or parts (e.g. facemask or mouthpiece one-way valve, etc.),
unless manufactured to prevent incorrect assembly;
NOTE See 6.3 Flow-direction sensitive components
b) the maximum fill volume on the liquid container.
If applicable, controls and instruments shall be legibly marked with:
a) the gas supply pressures in kilopascals (kPa);
b) the pressures in breathing systems in hectopascals (hPa);
c) the flow in litres per minute (l/min);
d) the air entrainment/oxygen dilution valves, in percent oxygen (% O );
and
e) the power and/or control devices marked with the relevant symbols.
Check conformance by inspection.
9.2.3 Marking on the packaging or individual pack
In addition to the marking requirements specified in 9.2, the packaging or individual pack shall:
a) differentiate between the same or similar products, both sterile and non-sterile, placed on the
market by the same manufacturer;
b) for nebulizing systems intended to be connected to an electrical power source be marked with the
nominal power expressed in Watts (W) or kilowatts (kW), as appropriate;
c) for nebulizing systems intended to be connected to the supply mains be marked with the rated
supply voltage(s) or rated voltage range(s) to which they can be connected, expressed in Volts (V).
Check conformance by inspection.
ISO 27427:2023(E)
9.3 Instructions for use
9.3.1 General information
In addition to the marking requirements specified in 9.2, components of nebulizing systems, shall be
accompanied by instructions for use, inserts, or accompanying documents that include:
a) a statement that the nebulizing system is or is not suitable for use in an anaesthetic breathing
system or a ventilator breathing system. See ISO 80601-2-12 and ISO 80601-2-13;
b) if applicable, the maximum temperature above ambient reached in the liquid chamber under all
operating conditions;
c) the types of liquid (e.g. solution, suspension and/or emulsion) the device is designed to nebulize;
d) the maximum fill volume;
e) if appropriate, the recommended fill volume for use;
f) if applicable, an indication of the spatial orientation (e.g. vertical, horizontal, inverted) at which the
nebulizer functions as intended;
g) a warning to the effect that using a solution, suspension, or emulsion different from that
recommended by the manufacturer, in particular, a suspension and/or high-viscosity solution,
can alter the particle size distribution curve, the mass median aerodynamic diameter (MMAD),
aerosol output, and/or aerosol output rate, which can then be different from those disclosed by the
manufacturer;
h) a statement that nebulizing systems intended to be connected to a power source (electrical or
pneumatic) shall be disconnected from the power source after use;
i) the mass of the nebulizer system in kilograms (kg);
j) the expected service lifetime of the reusable parts.
9.3.2 Performance disclosures
a) a statement to the effect that the following disclosures for performance are based upon testing that
utilizes adult ventilatory patterns and are likely to be different from those stated for paediatric or
infant populations;
b) the distribution of particles, in terms of percent of sampled mass, within each of the following size
ranges: % >5 µm, % 2 µm to 5 µm, and % <2 µm as outlined in Annex B when tested in accordance
with Annex D;
c) the mass median aerodynamic diameter (MMAD) and the geometric standard deviation (GSD) only
if the distribution is unimodal and log-normal, as derived from the particle size distribution curve,
when tested in accordance with Annex D;
d) the respirable fraction performance of the nebulizer, when tested in accordance with Annex D;
e) the aerosol output and aerosol output rate at the fill volume recommended by the manufacturer or
2 ml if a recommended fill volume is not provided, expressed as the mass of test substance collected
and the mass of test substance collected per minute, when tested in accordance with Annex C;
f) for gas-powered nebulizers, the aerosol output and aerosol output rate at the minimum, nominal, and
maximum driving gas flows with the corresponding pressures, when tested in accordance with
Annex C;
g) the percentage of fill volume emitted per minute (e.g. 20 % of fill volume per minute) as the aerosol
output in one minute divided by the fill volume recommended by the manufacturer or 2 ml if no fill
volume is recommended, when tested in accordance with Annex C;
ISO 27427:2023(E)
h) for gas-powered nebulizers, the percentage of fill volume emitted and percentage of fill volume emitted
per minute at the minimum, nominal, and maximum driving gas flows with the corresponding
pressures, when tested in accordance with Annex C;
i) the residual volume (in millilitres), when tested in accordance with Annex C;
NOTE Aerosol output fraction can then be calculated as the aerosol output divided by the mass of the
liquid placed in the nebulizer.
j) the test solution used to carry out the nebulizer performance type-tests in Annexes C and D;
k) if alternative test methods or test solutions have been used to demonstrate nebulizer performance, a
demonstration of equivalency shall be included in the technical documentation of the manufacturer
and shall be made available upon request;
l) for breath-actuated nebulizers, the method of operation and relevant sensitivity;
m) the maximum A-weighted sound pressure level, as derived from the test method in
IEC 60601-1:2005+AMD1: 2012+ AMD2: 2020, 9.6.2.1;
n) for nebulizers intended for use with ventilators, a statement to the effect that the measured aerosol
output and aerosol output rate are not intended to be used as the basis to determine the correct
dosage and that the aerosol output can differ when the nebulizer is used in combination with a
ventilator.
9.3.3 Driving gas supply information
a) the recommended driving gas(es);
b) the minimum and maximum recommended driving gas pressures and flows;
c) if applicable, a warning that oxygen or oxygen mixtures (with the O > 23 %) should not be used as
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the driving gas ;
d) if applicable, the composition and dryness specification for all gases to be supplied to the nebulizer;
ISO 27427:2023(E)
Annex A
(informative)
Rationale
A.1 General
This annex provides a concise rationale for the important requirements of this document and is intended
for use by those who are familiar with the subject of this document but who have not participated in
its development. An understanding of the reasons for the main requirements is considered essential
for its proper application. Furthermore, as clinical practices and technologies change, it is believed that
rationales for the present requirements will facilitate any revisions of this document necessitated by
those developments.
A.2 Rationale for Clause 1 — Scope
The essence of this document is to describe the characteristics and requirements of a general-purpose
nebulizer that can be used with a variety of medicinal substances. It is expected that the selection of
the nebulizer will be based on the requirements and characteristics developed in this document and
declared in the manufacturer's instructions for use.
Nasal deposition devices are excluded, as they are not considered general-purpose nebulizers.
There can be times when a device falls under the scope of either this document or ISO 20072. The
committee envisioned that the intended use of the product and the risk assessment of the device will
determine which standard the manufacturer chooses to qualify the device.
General-purpose nebulizers are considered to be semi-critical devices. Semi-critical devices are devices
that contact intact mucous membranes or non-intact skin. They do not ordinarily penetrate tissues or
otherwise enter normally sterile areas of the body. These devices should be reprocessed to be free from
all microorganisms.
A.3 Rationale for aerosol outlet port (3.3)
Mass is directly traceable to the active ingredient which is the fundamental deliverable. Volume is a
secondary measure because it is dependent on evaporation (see A.4).
A.4 Rationale for aerosol output rate (3.4)
The aerosol output rate can be greatly influenced by the evaporation of the aerosol droplets. The
following is provided to explain the sources and types of evaporation associated with nebulized aerosol:
Type 1 evaporation: Evaporation inside jet nebulizers. Compressed air (which is dry and on re-expansion
to atmosphere is always dry) draws up and mixes with nebulizer liquid container solution sprayed
within the nebulizer. The residence time of the de-compressed air (flow e.g. 6 l/min or 0,1 l/s) within
the nebulizer (internal volume, approximately 100 ml) is short (around 1/10 of a second). Even so, the
massive wet surface area of aerosol and rapid evaporation of solvent to the decompressed air ensures
that the air leaving the nebulizer is nearly saturated with water vapour (approximately 100 %). Further,
because of the latent heat lost to evaporation, the nebulizer liquid container cools relative to its initial
ambient temperature (from 20 °C to approximately 10 °C) and the aerosol-laden air leaves the nebulizer
in this cooled state. In this cooled saturated air cloud, the nebulized aerosol is stable until it either mixes
with ambient air (see Type 2 evaporation) or increases in temperature (see Type 3 evaporation).
ISO 27427:2023(E)
Type 2 evaporation: Evaporation of nebulized aerosol solvent when mixed with ambient air. Nebulized
aerosol leaving a jet or ultrasonic nebulizer exists in a cloud of 100 % relative humidity (RH) air. This
aerosol cloud is relatively stable with regard to evaporation until it mixes with ambient air. Mixing
is inherent in the design of constant output nebulizers where the nebulized aerosol is emitted into a
T-piece where the patient’s inhalation flow causes ambient air at lower humidity to be drawn into the
T-piece. The ambient air mixes with the nebulized aerosol-laden air and temporarily reduces the relative
humidity. The relative humidity quickly rises to 100 % by evaporation of water from the nebulized
aerosol. This evaporation effectively occurs in milliseconds, or using another reference, this evaporation
happens by the time the aerosol passes through the T-piece and tubing and exits from the nebulizer (or
very shortly thereafter). Of course, this volume loss implies that the size distribution of the nebulized
aerosol has shifted downwards. Further, this shift could not be constant, as smaller droplets have the
propensity to evaporate more readily than larger ones, so the distribution shift is not homogenous. In
any case, after the nebulized aerosol gives up solvent to re-saturate the air, the nebulized aerosol is again
stable. It is important to note that this form of evaporation is a feature of constant output nebulizers and
not “breath-enhanced nebulizers” whose design causes entrained ambient air to draw solvent vapour
from the nebulizer liquid container. For constant output nebulizers, the drier the ambient air, the greater
the effect of evaporation on the nebulized aerosol. Further, the lower the rate of aerosol output relative
to the flow of ambient air, the greater the effect of this evaporation on the nebulized aerosol.
Type 3 evaporation: Evaporation of nebulized aerosol solvent within a cascade impactor. Nebulized
aerosol, after mixing with ambient air, equilibrates to 100 % RH and is relatively stable. However, it
is cool (e.g. 10 °C) due to the latent heat of evaporation. The cool stable nebulized aerosol passes into
a cascade impactor. If the cascade impactor is at ambient temperature (e.g. 20 °C), the cooled air is
in contact with the cascade, which can act like a kind of radiator warming up the nebulized aerosol-
laden air. As the air warms up and travels through the cascade, the capacity of the warmer air to hold
moisture increases. In order to maintain 100 % RH, further evaporation occurs from the nebulized
aerosol during its flight through the cascade. As with the type 2 evaporation, the smaller the size of the
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particles in the nebulized aerosol, the more significant the losses and the greater the size change.
A.5 Rationale for percentage of fill volume emitted (3.15)
The percentage of fill volume emitted is an important value to be disclosed to the user, because it can
influence the decisions of dosage intended for delivery in terms related to the expected amount of drug
given to the patient.
The percentage of fill volume emitted per minute, when expressed as a rate, is an important value to
disclose to the user, because it can influence the decisions of dosage intended for delivery in terms
related to the expected duration of the therapy.
A.6 Rationale for residu
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