EN ISO 18562-4:2024
(Main)Biocompatibility evaluation of breathing gas pathways in healthcare applications - Part 4: Tests for leachables in condensate (ISO 18562-4:2024)
Biocompatibility evaluation of breathing gas pathways in healthcare applications - Part 4: Tests for leachables in condensate (ISO 18562-4:2024)
This document specifies tests for substances leached by liquid water condensing in gas pathways of a medical device, its parts or accessories, which are intended to provide respiratory care or supply substances via the respiratory tract to a patient in all environments. The chemical characterization methods described in this document apply to chemical substances that could leach from the medical device, its parts or accessories into the condensate. This document establishes verifiable acceptance criteria for these tests. The identity and quantity of each chemical released is intended for toxicological risk assessment as described in ISO 18562-1:2024.
This document addresses potential contamination of the gas stream arising from the gas pathways, which deliver breathing gas to the patient.
This document applies over the expected lifetime of the medical device in normal use and takes into account the effects of any intended processing.
This document does not address biological evaluation of the surfaces of gas pathways that have direct contact with the patient. The requirements for direct contact surfaces are found in the ISO 10993 series.
Medical devices, parts or accessories containing gas pathways that are addressed by this document include, but are not limited to, ventilators, anaesthesia workstations (including gas mixers), breathing systems, oxygen conserving devices, oxygen concentrators, nebulizers, low-pressure hose assemblies, humidifiers, heat and moisture exchangers, respiratory gas monitors, respiration monitors, masks, medical respiratory personal protective equipment, mouth pieces, resuscitators, breathing tubes, breathing systems filters, Y-pieces and any breathing accessories intended to be used with such devices. The enclosed chamber of an incubator, including the mattress, and the inner surface of an oxygen hood are considered to be gas pathways and are also addressed by this document.
This document does not address contamination already present in the gas supplied from the gas sources while medical devices are in normal use.
EXAMPLE Contamination arriving at the medical device from gas sources such as medical gas pipeline systems (including the non-return valves in the pipeline outlets), outlets of pressure regulators connected or integral to a medical gas cylinder, or room air taken into the medical device.
This document does not address contact with drugs or anaesthetic agents. If a medical device or accessory is intended to be used with anaesthetic agents or drugs, then additional testing can be required. This document is intended to quantify hazardous water-soluble substances that are leached from the medical device, its parts or accessories by condensate and then conveyed by that liquid to the patient.
Beurteilung der Biokompatibilität der Atemgaswege bei medizinischen Anwendungen - Teil 4: Prüfungen für herauslösbare Substanzen in Kondensaten (ISO 18562-4:2024)
Dieses Dokument legt Prüfungen für Substanzen fest, die durch flüssiges Wasser herausgelöst werden und in dem Kondensat enthalten sind, das sich in den Gaswegen eines Medizinprodukts sowie von dessen Teilen oder Zubehör, die für die Beatmung oder die Zufuhr von Stoffen über die Atemwege zu Patienten in allen Umgebungen vorgesehen sind, bildet. Die in diesem Dokument beschriebenen Verfahren zur chemischen Charakterisierung gelten für chemische Substanzen, die aus dem Medizinprodukt, seinen Teilen oder seinem Zubehör in das Kondensat gelangen könnten. Dieses Dokument erstellt verifizierbare Akzeptanzkriterien für diese Prüfungen. Die Identität und Menge jeder freigesetzten Chemikalie ist für die toxikologische Risikobeurteilung vorgesehen, wie in ISO 18562 1:2024 beschrieben.
Dieses Dokument behandelt die potenzielle Verunreinigung des Gasstroms durch die Gaswege, über die dem Patienten Atemgas zugeführt wird.
Dieses Dokument ist anwendbar für die zu erwartete Lebensdauer des Medizinprodukts bei bestimmungsgemäßem Gebrauch und berücksichtigt die Auswirkungen jeder beabsichtigten Aufbereitung.
Dieses Dokument behandelt nicht die biologische Beurteilung der Oberflächen von Gaswegen in direktem Kontakt mit dem Patienten. Die Anforderungen an Oberflächen in direktem Kontakt sind in der Normenreihe ISO 10993 enthalten.
Medizinprodukte, Teile oder Zubehör, die Gaswege enthalten, die in diesem Dokument behandelt werden, umfassen unter anderem Beatmungsgeräte, Anästhesie-Arbeitsplätze (einschließlich Gasmischern), Atemsysteme, Sauerstoff-Dosiersysteme, Sauerstoff-Konzentratoren, Vernebler, Niederdruck-Schlauchsysteme, Anfeuchter, Wärme- und Feuchtigkeitsaustauscher, Atemgas-Überwachungsgeräte, Atmungsüberwachungsgeräte, Masken, medizinische persönliche Atemschutzausrüstung, Mundstücke, Wiederbelebungsgeräte, Atemschläuche, Atemsystemfilter, Y-Stücke und jedes für den Einsatz mit Geräten vorgesehene Atemzubehör. Die umschlossene Kammer eines Inkubators einschließlich der Matratze und der inneren Oberfläche einer Sauerstoffhaube gelten als Gaswege und werden ebenfalls in diesem Dokument behandelt.
Dieses Dokument behandelt nicht die bereits in dem aus der Gasquelle zugeführten Gas vorhandene Verunreinigung während des bestimmungsgemäßen Gebrauchs von Medizinprodukten.
BEISPIEL In das Medizinprodukt eintretende Verunreinigungen aus den Gasquellen wie etwa Rohrleitungssystemen für medizinische Gase (einschließlich Rückschlagventilen an den Leitungsauslässen), Ausgänge von Druckminderern, die mit Flaschen für medizinische Gase verbunden oder in diese integriert sind, oder in das Medizinprodukt eintretende Raumluft.
Dieses Dokument behandelt nicht den Kontakt mit Medikamenten oder Anästhesiemitteln. Wenn ein Medizinprodukt oder Zubehör für den Einsatz mit Anästhesiemitteln oder Medikamenten vorgesehen ist, können zusätzliche Prüfungen erforderlich sein. Dieses Dokument dient dazu, gefahrbringende wasserlösliche Stoffe zu quantifizieren, die aus dem Medizinprodukt, seinen Teilen oder seinem Zubehör durch Kondensat herausgelöst und anschließend durch diese Flüssigkeit dem Patienten zugeführt werden können.
Évaluation de la biocompatibilité des chemins de gaz respiratoire utilisés dans le domaine de la santé - Partie 4: Essais concernant les relargables dans le condensat (ISO 18562-4:2024)
Le présent document spécifie les essais concernant les substances relarguées par l’eau liquide qui se condense dans les chemins de gaz utilisés dans un dispositif médical, ses parties ou ses accessoires, destinés à dispenser des soins respiratoires ou à fournir des substances par les voies respiratoires à un patient dans tous les types d’environnements. Les méthodes de caractérisation chimique décrites dans le présent document s’appliquent aux substances chimiques qui pourraient être relarguées du dispositif médical, de ses parties ou de ses accessoires dans le condensat. Le présent document établit des critères d’acceptation vérifiables de ces essais. L’identité et la quantité de chaque substance chimique libérée sont destinées à l’appréciation du risque toxicologique, tel que d’écrit dans l’ISO 18562-1:2024.
Le présent document traite de la contamination potentielle du flux gazeux provenant des chemins de gaz, qui délivrent du gaz respiratoire au patient.
Le présent document s’applique tout au long de la durée de vie prévue du dispositif médical en utilisation normale et prend en compte les effets associés à tout traitement prévu.
Le présent document ne traite pas de l’évaluation biologique des surfaces des chemins de gaz qui sont en contact direct avec le patient. Les exigences relatives aux surfaces en contact direct sont indiquées dans la série de normes ISO 10993.
Les dispositifs médicaux, leurs parties ou accessoires, contenant des chemins de gaz et faisant l’objet du présent document, comprennent, mais sans s’y limiter, les ventilateurs, les systèmes d’anesthésie (y compris les mélangeurs de gaz), les systèmes respiratoires, les économiseurs d’oxygène, les concentrateurs d’oxygène, les nébuliseurs, les flexibles de raccordement à basse pression, les humidificateurs, les échangeurs de chaleur et d’humidité, les moniteurs de gaz respiratoires, les moniteurs de respiration, les masques, les embouts buccaux, les appareils de réanimation, les tubes respiratoires, les filtres des systèmes respiratoires, les raccords en Y ainsi que tous les accessoires respiratoires destinés à être utilisés avec ces dispositifs médicaux. La chambre fermée d’un incubateur, y compris le matelas et la surface intérieure d’une cloche de Hood, est considérée comme un chemin de gaz et est également couverte par le présent document.
Le présent document ne traite pas de la contamination déjà présente dans le gaz provenant des sources de gaz lors d’une utilisation normale des dispositifs médicaux.
EXEMPLE La contamination arrivant dans le dispositif médical et provenant de sources de gaz telles que des systèmes de distribution de gaz médicaux (notamment les clapets antiretour situés sur les prises murales), les sorties des détendeurs raccordés ou intégrés à une bouteille de gaz médical, ou l’air ambiant envoyé dans le dispositif médical.
Le présent document ne traite pas du contact avec les médicaments ou les agents anesthésiques. Si un dispositif médical ou un accessoire est destiné à être utilisé avec des agents anesthésiants ou des médicaments, des essais supplémentaires peuvent être requis. Le présent document est destiné à quantifier les substances dangereuses solubles dans l’eau qui sont relarguées du dispositif médical, ses parties ou ses accessoires par un condensat et qui sont ensuite acheminées par ce liquide jusqu’au patient.
Ovrednotenje biokompatibilnosti vdihanega plina za uporabo v zdravstvu - 4. del: Preskusi izlužnin v kondenzatih (ISO 18562-4:2024)
Ta dokument določa preskuse za snovi, ki se izlužijo s kondenzacijo tekoče vode v poteh plinov medicinskega pripomočka, njegovih delov ali dodatne opreme, namenjene za oskrbo dihal ali dovajanje snovi prek dihalnega trakta pacientu v vseh okoljih. Metode kemijske karakterizacije, opisane v tem dokumentu, se uporabljajo za kemične snovi, ki bi se lahko iz medicinskega pripomočka, njegovih delov ali dodatne opreme izlužile v kondenzat. Dokument določa merila sprejemljivosti za te preskuse, ki jih je mogoče preveriti. Celotno ime in količine posameznih kemikalij, ki se sproščajo, so namenjene toksikološki oceni tveganja, kot je opisano v standardu ISO 18562-1:2024.
Ta dokument obravnava možnost kontaminacije toka plinov, ki izhaja iz poti plinov, prek katerih se dihalni plin dovaja pacientu.
Dokument se uporablja med pričakovano življenjsko dobo medicinskega pripomočka pri normalni uporabi in upošteva učinke predvidene obdelave.
Dokument tudi ne obravnava biološkega vrednotenja površin poti plinov, ki so v neposrednem stiku s pacientom. Zahteve za neposredne kontaktne površine so podane v skupini standardov ISO 10993.
Medicinski pripomočki, njihovi deli in dodatna oprema, ki vključujejo poti plinov, obravnavane v tem dokumentu, med drugim zajemajo ventilatorje, delovna mesta za anestezijo (vključno z mešalniki plinov), sisteme za vdihavanje, pripomočke za shranjevanje kisika, naprave za koncentriranje kisika, nebulatorje, nizkotlačne povezovalne cevi, vlažilnike zraka, izmenjevalnike toplote in vlage, monitorje dihalnih plinov, respiratorje, maske, medicinsko respiratorno osebno varovalno opremo, ustne nastavke, naprave za oživljanje, cevke za dihanje, filtre dihalnih sistemov, razdelilne elemente v obliki črke Y in katero koli dodatno opremo za dihanje, ki je namenjena za uporabo s takšnimi pripomočki. Zaprta komora inkubatorja, vključno z žimnico, in notranja površina kisikovega pokrova se štejeta za poti plinov ter sta prav tako obravnavani v tem dokumentu.
Ta dokument ne obravnava že prisotne kontaminacije v plinu, ki se dovaja iz virov plina med normalno uporabo medicinskih pripomočkov.
PRIMER: Kontaminacija, ki se prenese v medicinski pripomoček iz virov plina, kot so sistemi napeljav za medicinske pline (vključno z nepovratnimi ventili v odvodih cevi), odvodi regulatorjev tlaka, ki so povezani z jeklenko medicinskega plina oziroma so del nje, ali zrak v prostoru, ki vstopi v medicinski pripomoček.
Ta dokument ne obravnava stika z zdravili ali anestetiki. Če je medicinski pripomoček ali dodatna oprema namenjena uporabi z anestetiki ali zdravili, je morda potrebno dodatno preskušanje. Namen tega dokumenta je določiti količino nevarnih vodotopnih snovi, ki se izlužijo iz medicinskega pripomočka, njegovih delov ali dodatne opreme s kondenzatom, prek katerega se nato prenesejo v pacienta.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
01-december-2024
Nadomešča:
SIST EN ISO 18562-4:2020
Ovrednotenje biokompatibilnosti vdihanega plina za uporabo v zdravstvu - 4. del:
Preskusi izlužnin v kondenzatih (ISO 18562-4:2024)
Biocompatibility evaluation of breathing gas pathways in healthcare applications - Part 4:
Tests for leachables in condensate (ISO 18562-4:2024)
Beurteilung der Biokompatibilität der Atemgaswege bei medizinischen Anwendungen -
Teil 4: Prüfungen für herauslösbare Substanzen in Kondensaten (ISO 18562-4:2024)
Évaluation de la biocompatibilité des chemins de gaz respiratoire utilisés dans le
domaine de la santé - Partie 4: Essais concernant les relargables dans le condensat
(ISO 18562-4:2024)
Ta slovenski standard je istoveten z: EN ISO 18562-4:2024
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 18562-4
EUROPEAN STANDARD
NORME EUROPÉENNE
October 2024
EUROPÄISCHE NORM
ICS 11.040.10 Supersedes EN ISO 18562-4:2020
English Version
Biocompatibility evaluation of breathing gas pathways in
healthcare applications - Part 4: Tests for leachables in
condensate (ISO 18562-4:2024)
Évaluation de la biocompatibilité des chemins de gaz Beurteilung der Biokompatibilität der Atemgaswege
respiratoire utilisés dans le domaine de la santé - bei medizinischen Anwendungen - Teil 4: Prüfungen
Partie 4: Essais concernant les relargables dans le für herauslösbare Substanzen in Kondensaten (ISO
condensat (ISO 18562-4:2024) 18562-4:2024)
This European Standard was approved by CEN on 15 March 2024.
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
© 2024 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 18562-4:2024 E
worldwide for CEN national Members.
Contents Page
European foreword . 3
Annex ZA (informative) Relationship between this European standard and the General
Safety and Performance Requirements of Regulation (EU) 2017/745 aimed to be
covered. 4
European foreword
This document (EN ISO 18562-4:2024) 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 April 2025, and conflicting national standards shall be
withdrawn at the latest by April 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 18562-4:2020.
This document has been prepared under a standardization request addressed to CEN by the European
Commission. The Standing Committee of the EFTA States subsequently approves these requests for its
Member States.
For the relationship with EU Legislation, see informative Annex ZA, which is an integral part of this
document.
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 18562-4:2024 has been approved by CEN as EN ISO 18562-4:2024 without any
modification.
Annex ZA
(informative)
Relationship between this European standard and the General Safety and
Performance Requirements of Regulation (EU) 2017/745 aimed to be
covered
This European standard has been prepared under M/575 to provide one voluntary means of
conforming to the General Safety and Performance Requirements of Regulation (EU) 2017/745 of 5
April 2017 concerning medical devices [OJ L 117] and to system or process requirements including
those relating to quality management systems, risk management, post-market surveillance systems,
clinical investigations, clinical evaluation or post-market clinical follow-up.
Once this standard is cited in the Official Journal of the European Union under that Regulation,
compliance with the normative clauses of this standard given in Table ZA.1 confers, within the limits of
the scope of this standard, a presumption of conformity with the corresponding General Safety and
Performance Requirements of that Regulation, and associated EFTA Regulations.
Where a definition in this standard differs from a definition of the same term set out in Regulation (EU)
2017/745, the differences shall be indicated in Table ZA.3 in this Annex Z. For the purpose of using this
standard in support of the requirements set out in Regulation (EU) 2017/745, the definitions set out in
this Regulation prevail.
Where the European standard is an adoption of an International Standard, the scope of this standard
can differ from the scope of the European Regulation that it supports. As the scope of the applicable
regulatory requirements differ from nation to nation and region to region, the standard can only
support European regulatory requirements to the extent of the scope of the European regulation for
medical devices (EU) 2017/745.
For application of this European standard under Regulation (EU) 2017/745, its scope is limited to
medical devices for use with human patients. This affects all clauses of this European standard.
NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk
management process needs to be in compliance with Regulation (EU) 2017/745. This means that risks have to be
‘reduced as far as possible’, ‘reduced to the lowest possible level’, ‘reduced as far as possible and appropriate’,
‘removed or reduced as far as possible’, ‘eliminated or reduced as far as possible’, ’removed or minimized as far as
possible’, or ‘minimized’, according to the wording of the corresponding General Safety and Performance
Requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with General Safety
and Performance Requirements 1, 2, 3, 4, 5, 8, 9, 10, 11, 14, 16, 17, 18, 19, 20, 21 and 22 of the Regulation.
NOTE 3 When a General Safety and Performance Requirement does not appear in Table ZA.1, it means that it is
not addressed by this European Standard.
Table ZA.1 — Correspondence between this European standard and Annex I of Regulation (EU)
2017/745 [OJ L 117] and to system or process requirements including those relating to quality
management systems, risk management, post-market surveillance systems, clinical investigations,
clinical evaluation or post-market clinical follow-up
General Safety and
Clause(s) / sub-clause(s)
Performance Requirements of Remarks / Notes
of this EN
Regulation (EU) 2017/745
10.1 a) Clause 4, Clause 5, Clause 6 This requirement is only partly
covered by this document, since the
standard does not provide
requirements on manufacture.
However, this standard provides a
means to assess risks to the patient
associated with the toxicity of the
condensate from the gas pathways of
manufactured medical devices. Other
forms of toxicity and flammability are
not covered.
10.1 b) Clause 4, Clause 5, Clause 6 This requirement is only partly
covered by this document, since the
standard does not provide
requirements on manufacture.
However, this standard provides a
means to assess risks to the patient
associated with the toxicity of the
condensate from the gas pathways of
manufactured medical devices.
10.2 Clause 4, Clause 5, Clause 6 This requirement is only partly
covered by this document, since the
standard does not provide
requirements on manufacture and
packaging. However, this standard
provides a means to assess risks to
the patient associated with the
toxicity of the condensate from the
gas pathways of manufactured
medical devices. Risks to other
persons involved in the transport,
storage and use of the devices are not
covered.
General Safety and
Clause(s) / sub-clause(s)
Performance Requirements of Remarks / Notes
of this EN
Regulation (EU) 2017/745
10.3 Clause 4, Clause 5, Clause 6 This requirement is only partly
covered by this document, since the
standard does not provide
requirements on manufacture. Only
the aspects relating to contamination
of the gas pathways by contact with
water are covered.
Risks to the patient associated with
medicinal substances added to the
gas stream are not covered.
10.4.1 (first paragraph only) Clause 4, Clause 5, Clause 6 This requirement is only partly
covered by this document, since the
standard does not provide
requirements on manufacture.
However, this standard provides a
means to assess risks to the patient
associated with the toxicity of the
condensate from the gas pathways of
manufactured medical devices. Other
forms of toxicity are not covered.
14.2 c) Clause 4, Clause 5, Clause 6 This requirement is only partly
covered by this document, since the
standard does not provide
requirements on manufacture.
However, this standard provides a
means to assess risks to the patient
associated with the toxicity of the
condensate from the gas pathways of
manufactured medical devices.
WARNING 1: Presumption of conformity stays valid only as long as a reference to this European
standard is maintained in the list published in the Official Journal of the European Union. Users of this
standard should consult frequently the latest list published in the Official Journal of the European
Union.
WARNING 2: Other Union legislation may be applicable to the product(s) falling within the scope of this
standard.
Table ZA.2 — Applicable Standards to confer presumption of conformity as described in this
Annex ZA
Column 1 Column 2 Column 3 Column 4
Reference in International Standard
Title Corresponding European
Clause 2 Edition
Standard Edition
ISO 10993 1:2018 ISO 10993 1:2018 Biological evaluation of EN ISO 10993 1:2020
medical devices — Part 1:
Evaluation and testing
within a risk management
process
ISO 10993-5:2009 ISO 10993-5:2009 Biological evaluation of EN ISO 10993-5:2009
medical devices — Part 5:
Tests for in vitro
cytotoxicity
ISO 10993-10:2021 ISO 10993-10:2021 Biological evaluation of EN ISO 10993-10:2023
medical devices — Part
10: Tests for skin
sensitization
ISO 10993-12:2021 ISO 10993-12:2021 Biological evaluation of EN ISO 10993-12:2021
medical devices — Part
12: Sample preparation
and reference materials
ISO 10993-18:2020 ISO 10993-18:2020 Biological evaluation of EN ISO 10993-18:2020
+AMD1:2022 +AMD1:2022 medical devices — Part +A1:2023
18: Chemical
characterization of
medical device materials
within a risk management
process
ISO 10993-23:2021 ISO 10993-23:2021 Biological evaluation of EN ISO 10993-23:2021
medical devices — Part
23: Tests for irritation
a
ISO 18562-1:2024 ISO 18562-1:2024 Biocompatibility EN ISO 18562-1:2024
evaluation of breathing
gas pathways in
healthcare applications
— Part 1: Evaluation and
testing within a risk
management process
ICH Q3D(R2):2022 — ICH guideline Q3D (R2) —
for elemental impurities
The documents listed in the Column 1 of Table ZA.2, in whole or in part, are normatively referenced in
this document, i.e. are indispensable for its application. The achievement of the presumption of
conformity is subject to the application of the edition of Standards as listed in Column 4 or, if no
European Standard Edition exists, the International Standard Edition given in Column 2 of Table ZA.2.
Table ZA.3 — Prevailing terms of Regulation (EU) 2017/745
for use of this European standard under that Regulation
Term used Clause / Article in (EU) Differences / Consequences
in this EN sub- 2017/745 that
clause defines or uses this
where term
this term
is
defined
in this EN
N/A N/A N/A No legally relevant terms are defined in this Standard
International
Standard
ISO 18562-4
Second edition
Biocompatibility evaluation
2024-03
of breathing gas pathways in
healthcare applications —
Part 4:
Tests for leachables in condensate
Évaluation de la biocompatibilité des chemins de gaz respiratoire
utilisés dans le domaine de la santé —
Partie 4: Essais concernant les relargables dans le condensat
Reference number
ISO 18562-4:2024(en) © ISO 2024
ISO 18562-4:2024(en)
© ISO 2024
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
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Published in Switzerland
ii
ISO 18562-4:2024(en)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 General principles . 2
5 Leachables in condensate . 3
5.1 Identifying applicable gas pathway surfaces .3
5.2 Determining if testing is required .3
5.3 Test methods .4
5.3.1 General .4
5.3.2 Sample collection .5
5.3.3 Chemical characterization of leachables in condensate.6
5.3.4 Calculation of tolerable exposure .7
5.3.5 Calculation of exposure dose estimate .7
5.3.6 Risk assessment .7
5.3.7 Biological evaluation according to ISO 10993 standards .8
6 Reporting . 9
Annex A (informative) Rationale and guidance . 10
Annex B (informative) Reference to the IMDRF essential principles and labelling guidances .12
Annex C (informative) Reference to the essential principles .13
Annex D (informative) Terminology — Alphabetized index of defined terms. 14
Bibliography .15
iii
ISO 18562-4:2024(en)
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 document 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).
ISO draws attention to the possibility that the implementation of this document may involve the use of (a)
patent(s). ISO takes no position concerning the evidence, validity or applicability of any claimed patent
rights in respect thereof. As of the date of publication of this document, ISO had not received notice of (a)
patent(s) which may be required to implement this document. However, implementers are cautioned that
this may not represent the latest information, which may be obtained from the patent database available at
www.iso.org/patents. ISO shall not be held responsible for identifying any or all such patent rights.
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 3, Respiratory devices and related equipment used for patient care 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 second edition cancels and replaces the first edition (ISO 18562-4:2017), which has been technically
revised.
The main changes are as follows:
— added informative mapping annexes to relevant regulatory requirements;
— clarified terms and definitions used in the document;
— clarified the stepwise test procedure;
— required determination of volume of condensate that can reach the patient; and
— required calculating resulting exposure dose.
A list of all parts in the ISO 18562 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.
iv
ISO 18562-4:2024(en)
Introduction
This document is intended to protect patients connected to medical devices from harmful amounts of
substances that might be dissolved in water that has condensed in the gas pathways of those medical devices.
This document represents the application of the best-known science by addressing the risks from potentially
hazardous substances in the condensate being conveyed to the patient by the gas pathway. The condensate
itself will be distilled water, having condensed from the vapour phase. But substances from within the
medical device could leach into the liquid water (condensate) present in the breathing system.
This document is intended to cover the biological evaluation of gas pathways of medical devices within a
risk management process, as part of the overall medical device evaluation and development. This approach
combines the review and evaluation of existing data from all sources with, where necessary, the selection
and application of additional tests.
In general, the ISO 10993 series is intended to cover the biological evaluation of medical devices. However,
the ISO 10993 series does not appropriately address the biological evaluation of the gas pathways of medical
devices.
It is not within the scope of this document to address contamination arising from the source of the breathing
gases entering such medical devices, but rather only address the potential contamination generated from
within the medical device itself. This contamination might be from the original manufacturing process or
generated by the medical device itself during use.
This document is concerned with substances that could be conveyed to the patient by liquid condensate
forming in the medical device and then subsequently reaching the patient. Potentially harmful substances
that could be found in condensate include organic compounds and elements (such as metals). Condensate
management is part of most healthcare institution protocols, with the primary aim of preventing the
condensate reaching the patient in the first place. The absolute volume of liquid reaching a patient by this
route should therefore be low, but it might happen. This document outlines tests for substances contained in
the liquid.
The methods to determine the acceptable levels of contamination are contained in ISO 18562-1.
This document has been prepared in consideration of:
— the Essential Principles of Safety and Performance of Medical Devices and IVD Medical Devices, IMDRF/
[16]
GRRP WG/N47:2018 as indicated in Annex B;
[17]
— the Labelling Principles for Medical Devices and IVD Medical Devices, IMDRF/GRRP WG/N52:2019 as
indicated in Annex B;
— the essential principles of safety and performance of a medical device according to ISO 16142-1:2016 as
indicated in Annex C; and
— the general safety and performance requirements of a medical device according to regulation
[18]
(EU) 2017/745 .
In this document, the following verbal forms are used:
— “shall” indicates a requirement;
— “should” indicates a recommendation;
— “may” indicates a permission;
— "can" indicates a possibility or capability.
v
International Standard ISO 18562-4:2024(en)
Biocompatibility evaluation of breathing gas pathways in
healthcare applications —
Part 4:
Tests for leachables in condensate
1 Scope
This document specifies tests for substances leached by liquid water condensing in gas pathways of a medical
device, its parts or accessories, which are intended to provide respiratory care or supply substances via the
respiratory tract to a patient in all environments. The chemical characterization methods described in this
document apply to chemical substances that could leach from the medical device, its parts or accessories
into the condensate. This document establishes verifiable acceptance criteria for these tests. The identity
and quantity of each chemical released is intended for toxicological risk assessment as described in
ISO 18562-1:2024.
This document addresses potential contamination of the gas stream arising from the gas pathways, which
deliver breathing gas to the patient.
This document applies over the expected lifetime of the medical device in normal use and takes into account
the effects of any intended processing.
This document does not address biological evaluation of the surfaces of gas pathways that have direct contact
with the patient. The requirements for direct contact surfaces are found in the ISO 10993 series.
Medical devices, parts or accessories containing gas pathways that are addressed by this document include,
but are not limited to, ventilators, anaesthesia workstations (including gas mixers), breathing systems,
oxygen conserving devices, oxygen concentrators, nebulizers, low-pressure hose assemblies, humidifiers,
heat and moisture exchangers, respiratory gas monitors, respiration monitors, masks, medical respiratory
personal protective equipment, mouth pieces, resuscitators, breathing tubes, breathing systems filters,
Y-pieces and any breathing accessories intended to be used with such devices. The enclosed chamber of an
incubator, including the mattress, and the inner surface of an oxygen hood are considered to be gas pathways
and are also addressed by this document.
This document does not address contamination already present in the gas supplied from the gas sources
while medical devices are in normal use.
EXAMPLE Contamination arriving at the medical device from gas sources such as medical gas pipeline systems
(including the non-return valves in the pipeline outlets), outlets of pressure regulators connected or integral to a
medical gas cylinder, or room air taken into the medical device.
This document does not address contact with drugs or anaesthetic agents. If a medical device or accessory is
intended to be used with anaesthetic agents or drugs, then additional testing can be required. This document
is intended to quantify hazardous water-soluble substances that are leached from the medical device, its
parts or accessories by condensate and then conveyed by that liquid to the patient.
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 18562-4:2024(en)
ISO 10993-1:2018, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
ISO 10993-5:2009, Biological evaluation of medical devices — Part 5: Tests for in vitro cytotoxicity
ISO 10993-10:2021, Biological evaluation of medical devices — Part 10: Tests for skin sensitization
ISO 10993-12:2021, Biological evaluation of medical devices — Part 12: Sample preparation and reference
materials
ISO 10993-18:2020+AMD1: 2022, Biological evaluation of medical devices — Part 18: Chemical characterization
of materials within a risk management process
ISO 10993-23:2021, Biological evaluation of medical devices — Part 23: Tests for irritation
ISO 18562-1:2024, Biocompatibility evaluation of breathing gas pathways in healthcare applications — Part 1:
Evaluation and testing within a risk management process
1)
ICH Q3D(R2):2022, Guideline for elemental impurities
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 18562-1:2024 and the following
apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
NOTE For convenience, an alphabetized index of all defined terms and their sources used in this document are
given in Annex D.
3.1
exaggerated extraction
extraction that is intended to result in a greater amount of a chemical constituent being released as compared
to the amount generated under the simulated conditions of use
Note 1 to entry: It is important to ensure that the exaggerated extraction does not result in a chemical change of the
material.
[SOURCE: ISO 10993-12:2021, 3.3]
3.2
extractable
substance that is released from a medical device or material of construction when the medical device or
material is extracted using laboratory extraction conditions and vehicles
[SOURCE: ISO 10993-18:2020+AMD1: 2022, 3.16]
4 General principles
All gas pathways that are exposed to water or that are exposed to humidified gas, and within which water
vapour can condense and subsequently reach the patient in liquid form shall be evaluated using the principles
detailed in ISO 18562-1:2024.
NOTE Some parts of the expiratory gas pathways can allow condensed water to settle, and subsequently flow
under gravity back towards the patient.
1) Available at: https:// database .ich .org/ sites/ default/ files/ Q3D -R2 _Guideline _Step4 _2022 _0308 .pdf
ISO 18562-4:2024(en)
5 Leachables in condensate
5.1 Identifying applicable gas pathway surfaces
a) A medical device, its parts or accessories shall not add leachables to the condensate at levels that create
an unacceptable risk to the patient.
b) All gas pathways of medical devices or accessories in normal use and normal condition shall be evaluated
for leachables in condensate, where
— gas in the gas pathway can reach 100 % saturation with water at some point in the gas pathway,
— condensate can form on or flow along the gas pathway surfaces, and
— that liquid condensate can reach the patient.
NOTE 1 Some parts of the expiratory gas pathways can allow condensed water to settle, and
subsequently flow under gravity back towards the patient.
NOTE 2 Condensate, which in itself is water, can form in gas pathways and can take the form of liquid
drops or a film of water on the gas pathway walls. This liquid water can extract substances from the materials
of the walls that would not be extracted by the breathing gas alone. If this liquid condensate can reach the
patient, it could potentially convey harmful substances to the patient.
1) Reasonably foreseeable use errors that can affect condensate reaching the patient should also be
considered one use error at a time.
NOTE 3 Reasonably foreseeable use errors can include incorrect equipment set up.
c) Containers for water (e.g. water tanks) where that water in liquid form can reach the gas pathway and
then reach the patient shall be evaluated for leachables in the water.
5.2 Determining if testing is required
a) The evaluation shall use the risk management process to assess if testing is required.
b) Sections of the gas pathway from which the patient cannot be exposed to condensate need not be tested.
EXAMPLE An exhaust gas pathway separated by a check valve preventing backflow of condensate to the
patient.
1) The rationale for excluding gas pathways where the patient cannot be exposed to condensate shall
be documented in the report.
c) If the medical device part or accessory is identical or sufficiently similar in formulation, geometry,
manufacturing processes or application processes, packaging and any subsequent processing to an
existing medical device with the same intended use and worst case clinically relevant conditions, an
evaluation may conclude that no further testing is required. Refer to ISO 18562-1:2024, Figure 2 and
ISO 10993-18:2020+AMD1: 2022, C.2.
NOTE 1 Manufacturing and application processes include hygienic processing (i.e., cleaning/disinfection/
sterilization either prior to use or between uses).
1) Any differences between the medical device part or accessory and existing medical device part or
accessory
i) shall be documented in the report, with
ISO 18562-4:2024(en)
ii) a rationale provided in the report for why the changes do not negatively impact the condensate
volume and leachable profile.
d) If the medical device under evaluation has already been evaluated as an external communicating medical
device with contact to tissue/bone/dentin in accordance with ISO 10993-1:2018, then the tests in 5.3
need not be performed.
EXAMPLE 2 A tracheal tube, because of its direct contact with the patient, is evaluated utilizing ISO 10993-1.
In this case, the tests of this document are not required.
NOTE 2 Some authorities having jurisdiction might require the tests of 5.3 if the medical device is intended for
use on particularly vulnerable patient populations, such as neonates.
e) If the risk management process determines that testing is required, the tests of 5.3 shall be performed.
5.3 Test methods
5.3.1 General
The condensate evaluation of gas pathways shall include
a) establishing the worst-case clinically relevant maximum volume of condensate that can be conveyed to
the patient.
NOTE 1 There is guidance and rationale for this list item contained in Clause A.2.
1) This shall be done by one of the following:
i) experimentally determining in normal use and normal condition under worst-case clinically
relevant parameters (e.g., temperature, gas flowrate, etc.) the volume of condensate reaching
the patient; or
I) Normal use shall include reasonably foreseeable use errors that contribute to condensate
reaching the patient, one use error at a time (e.g., selection of incorrect settings for a patient
or incorrect equipment set up).
NOTE 2 Normal use assumes the implementation of specific measures described in the instructions
for use intended to avoid or reduce patient exposure to condensate. The worst-case amount of condensate
that can be formed and reach the patient from simultaneous use errors is not relevant. A lower volume can
then be justified for the toxicological risk assessment.
II) All reasonably foreseeable use errors shall be documented in the report with the respective
condensate volumes generated.
III) If the experimentally determined volume of condensate reaching the patient establishes
that no more than 0,1 ml in 24 h reaches the patient under worst case clinical conditions,
then no further testing is required.
IV) The experimental methods shall be justified in the report.
NOTE 3 Breathing gas pathways are systems that commonly include multiple medical devices and
accessories, often from different manufacturers. The subject medical device or accessory needs to be evaluated
in its intended use as part of a system and might not be the part that determines the volume of condensate
forming and being delivered to the patient.
ii) by justified arguments in the report.
NOTE 4 Some authorities having jurisdiction can require experimental testing.
b) the chemical characterization of the leachables in the condensate.
c) performing a toxicological risk assessment on the leachables in condensate with respect to systemic
effects.
ISO 18562-4:2024(en)
NOTE 5 For guidance on which effects (endpoints) are covered in a toxicological risk assessment, see Annex A of
ISO 10993-1:2018.
NOTE 6 Concerns regarding materials mediated pyrogenicity can be addressed by using well known materials
for which a pyrogenic effect is not expected.
d) condensate testing of the leachables with respect to the following local endpoints:
1) cytotoxicity;
2) sensitization; and
3) irritation.
5.3.2 Sample collection
a) The duration of sample collection shall be justified and documented in the report based on worst-case
clinically relevant patient exposure in normal use.
b) If a medical device is intended to be used repeatedly for long-term duration, the extraction protocol shall
be adequate to assess the impact from repeated use (over the expected lifetime).
NOTE 1 Some authorities having jurisdiction can require aqueous exhaustive extraction for prolonged and long-
term exposure medical devices or accessories.
c) For chemical characterization, the sample shall be collected by:
1) producing and collecting condensate under worst-case clinically relevant conditions; or
i) the worst-case clinically relevant conditions shall be justified by rationale, and
ii) the rationale shall be documented in the report.
2) performing an aqueous extraction on the gas contact surface materials using exaggerated extraction
(e.g., higher temperature or longer duration).
NOTE 2 Some authorities having jurisdiction can require exaggerated extraction to include higher
temperature and longer duration relative to clinical use conditions.
i) If performing the exaggerated extraction on just the gas contact surface is not technically
feasible, the extraction may be performed on the medical device or component as a whole,
ii) When the exaggerated extraction is performed on the medical device or component as a whole,
the calculated surface area shall be limited to the gas contact surface area.
d) The sample collection shall facilitate the determination of the worst-case exposure dose (in one day).
1) The worst-case exposure dose shall be justified by rationale.
NOTE 3 There is guidance and rationale for this list item contained in Clause A.2.
2) The rationale shall be documented in the report.
e) For biological testing for irritation and sensitization, the sample shall be collected by performing a water
extraction on the internal gas contact surfaces identified in 5.1 b), in accordance with ISO 10993-12:2021,
Clause 10.
NOTE 4 There is guidance or rationale for this list item contained in Clause A.2.
1) Saline extraction shall not be used.
ISO 18562-4:2024(en)
2) If performing the exaggerated extraction on just the gas contact surface is not technically feasible,
the extraction may be performed on the medical device or accessory as a whole.
f) For biological testing for cytotoxicity on the medical device or accessory itself, the sample shall be
collected by performing an extraction in cell culture medium or water on the internal gas contact
surfaces in accordance with ISO 10993-5:2009, 4.2.
1) If performing the exaggerated extraction on just the gas contact surface is not technically feasible,
the extraction may be performed on the medical device or accessory as a whole.
2) Where cytotoxicity testing is conducted on a water extract of components including exposed
metallic parts, the concentration of the cell culture medium shall be corrected to account for
dilution (e.g., use of 10X MEM solutions).
NOTE 5 There is guidance and rationale for this list item contained in Clause A.2.
NOTE 6 Some authorities having jurisdiction require that the extraction is performed with cell culture
medium.
g) For biological testing for cytotoxicity on the condensate, the sample collection conditions shall represent
worst-case clinically relevant conditions including temperature and duration of contact.
h) This document is not intended to be prescriptive in the selection of medical device configuration, test
methods or the conditions used to produce the sample. Choices shall be justified and documented in the
report.
5.3.3 Chemical characterization of leachables in condensate
a) Identify and quantify in the condensate or extract,
1) organic leachable substances, using appropriate analytical techniques such as
i) gas chromatography-mass spectrometry (GC/MS); or
ii) liquid chromatography - mass spectrometry (LC/MS).
2) elemental (e.g. metal ions) leachable substances, using appropriate analytical techniques such as
i) inductively coupled plasma/mass spectroscopy (ICP-MS); or
ii) inductively coupled plasma atomic emission spectroscopy (ICP-AES); or
iii) a combination of ICP-MS and ICP-AES.
NOTE 1 Elemental leachables are sometimes ref
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