EN ISO 18562-1:2020

Biocompatibility evaluation of breathing gas pathways in healthcare applications - Part 1: Evaluation and testing within a risk management process (ISO 18562-1:2017)

ISO 18562-1:2017 specifies:
-      the general principles governing the biological evaluation within a risk management process of the 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 general categorization of gas pathways based on the nature and duration of their contact with the gas stream;
-      the evaluation of existing relevant data from all sources;
-      the identification of gaps in the available data set on the basis of a risk analysis;
-      the identification of additional data sets necessary to analyse the biological safety of the gas pathway;
-      the assessment of the biological safety of the gas pathway.
ISO 18562-1:2017 covers general principles regarding biocompatibility assessment of medical device materials, which make up the gas pathway, but does not cover biological hazards arising from any mechanical failure, unless the failure introduces a toxicity risk (e.g. by generating particulates). The other parts of ISO 18562 cover specific tests that address potentially hazardous substances that are added to the respirable gas stream and establish acceptance criteria for these substances.
ISO 18562-1:2017 addresses potential contamination of the gas stream arising from the gas pathways within the medical device, which might then be conducted to the patient.
ISO 18562-1:2017 applies over the expected service life of the medical device in normal use and takes into account the effects of any intended processing or reprocessing.
ISO 18562-1:2017 does not address biological evaluation of the surfaces of medical devices that are in 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 equipment, oxygen concentrators, nebulizers, low-pressure hose assemblies, humidifiers, heat and moisture exchangers, respiratory gas monitors, respiration monitors, masks, mouth pieces, resuscitators, breathing tubes, breathing system filters and Y-pieces as well as any breathing accessories intended to be used with such medical 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.
ISO 18562-1:2017 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 is not addressed by ISO 18562 (all parts).
Future parts might be added to address other relevant aspects of biological testing including additional contamination that might arise from the gas pathway because of the presence of drugs and anaesthetic agents added to the gas stream.
NOTE 1       Some authorities having jurisdiction require evaluation of these risks as part of a biological evaluation.
NOTE 2       This document has been prepared to address the relevant essentia

Beurteilung der Biokompatibilität der Atemgaswege bei medizinischen Anwendungen - Teil 1: Beurteilung und Prüfung innerhalb eines Risikomanagement-Prozesses (ISO 18562-1:2017)

Dieses Dokument legt Folgendes fest:
- die allgemeinen Grundsätze für die biologische Beurteilung in einem RISIKOMANAGEMENTPROZESS von GASWEGEN eines MEDIZINPRODUKTES sowie von dessen Teilen oder ZUBEHÖR, die für die Beatmung oder die Zufuhr von Stoffen über die Atemwege eines PATIENTEN in allen Umgebungen vorgesehen sind;
- die allgemeine Klassifizierung von GASWEGEN auf der Grundlage der Art und Dauer ihres Kontakts mit dem Gasstrom;
- die Beurteilung vorhandener relevanter Daten aus allen Quellen;
- die Identifizierung von Lücken in den verfügbaren Datensätzen auf der Grundlage einer RISIKOANALYSE;
- die Identifizierung zusätzlicher Datensätze, die für die Analyse der biologischen Sicherheit des GASWEGS erforderlich sind;
- die Bewertung der biologischen Sicherheit des GASWEGS.
Dieses Dokument behandelt die allgemeinen Grundsätze der Beurteilung der BIOKOMPATIBILITÄT von Werkstoffen von MEDIZINPRODUKTEN, aus denen der GASWEG besteht, jedoch nicht die aus einem mechanischen Versagen entstehenden biologischen GEFÄHRDUNGEN, sofern das Versagen kein ToxizitätsRISIKO verursacht (z. B. durch Erzeugen von PARTIKELN). Die anderen Teile von ISO 18562 behandeln spezifische Prüfungen, die potenziell gefährliche Stoffe betreffen, die dem Atemgasstrom hinzugefügt werden, und erstellen Akzeptanzkriterien für diese Stoffe.
Dieses Dokument behandelt die potenzielle Verunreinigung des Gasstroms aus den GASWEGEN innerhalb des MEDIZINPRODUKTS, die anschließend dem PATIENTEN zugeführt werden könnte.
Dieses Dokument gilt für die ZU ERWARTENDE BETRIEBS-LEBENSDAUER des MEDIZINPRODUKTS bei BESTIMMUNGSGEMÄßEM GEBRAUCH und berücksichtigt die Auswirkungen jeder beabsichtigten Aufbereitung oder Wiederaufbereitung.
Dieses Dokument behandelt nicht die biologische Beurteilung der Oberflächen von MEDIZINPRODUKTEN 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, Mundstücke, Wiederbelebungsgeräte, Atemschläuche, Atemsystemfilter, Y Stücke sowie jedes für den Einsatz mit solchen MEDIZINPRODUKTEN 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 in den Leitungsauslässen), Ausgänge von Druckminderen, die mit Flaschen für medizinische Gase verbunden oder in diese integriert sind, oder in das MEDIZINPRODUKT eintretende Raumluft werden nicht in ISO 18562 (alle Teile) behandelt.
Zukünftige Teile könnten ergänzt werden, um andere relevante Aspekte der biologischen Prüfung zu behandeln, einschließlich zusätzlicher Verunreinigungen, die aus dem GASWEG durch die Anwesenheit von Medikamenten und Anästhesiemitteln, die dem Gasstrom hinzugefügt werden, entstehen könnten.
ANMERKUNG 1 Einige ZUSTÄNDIGE BEHÖRDEN fordern die Bewertung dieser RISIKEN als Teil einer biologischen Beurteilung.
ANMERKUNG 2 Dieses Dokument wurde erstellt, um die relevanten grundlegenden Prinzipien der Sicherheit und Leistungsmerkmale zu behandeln, wie in Anhang B angegeben.

Évaluation de la biocompatibilité des voies de gaz respiratoires dans les applications de soins de santé - Partie 1: Évaluation et essais au sein d'un processus de gestion du risque (ISO 18562-1:2017)

ISO 18562-1:2017 spécifie:
-      les principes généraux gouvernant l'évaluation biologique au sein d'un processus de gestion du risque des chemins de gaz utilisés dans un dispositif médical, ses parties ou ses accessoires, qui sont destinés à dispenser des soins respiratoires ou à fournir des substances par les voies respiratoires à un patient dans tous les types d'environnements;
-      la classification générale des chemins de gaz, fondée sur la nature et la durée de leur contact avec le flux gazeux;
-      l'évaluation de toutes les données existantes;
-      l'identification de manques dans les ensembles de données disponibles sur la base d'une analyse de risque;
-      l'identification d'ensembles de données supplémentaires nécessaires à l'analyse de la sécurité biologique du chemin de gaz;
-      l'évaluation de la sécurité biologique du chemin de gaz.
ISO 18562-1:2017 couvre les principes généraux relatifs à l'évaluation de la biocompatibilité des matériaux constituant un dispositif médical, qui composent le chemin de gaz, mais ne couvre pas les phénomènes dangereux biologiques causés par une défaillance mécanique, à moins que celle-ci n'introduise un risque de toxicité (par exemple en générant des particules). Les autres parties de l'ISO 18562 couvrent des essais spécifiques traitant des substances potentiellement dangereuses qui sont ajoutées au flux de gaz respirable et établissant les critères d'acceptation de ces substances.
ISO 18562-1:2017 traite de la contamination potentielle du flux gazeux provenant des chemins de gaz utilisés dans un dispositif médical, qui pourrait ensuite être acheminé jusqu'au patient.
ISO 18562-1:2017 s'applique pour la durée de vie prévue du dispositif médical en utilisation normale et prend en compte les effets associés à tout traitement ou retraitement prévu.
ISO 18562-1:2017 ne traite pas de l'évaluation biologique des surfaces des dispositifs médicaux 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 de système respiratoire, 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, sont considérés comme des chemins de gaz et sont également couverts par le présent document.
ISO 18562-1:2017 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 anti-retour situés sur les prises murales), les sorties des détendeurs raccordés ou intégrés à une bouteille de gaz médica

Ovrednotenje biokompatibilnosti vdihanega plina za uporabo v zdravstvu - 1. del: Ovrednotenje in preskušanje znotraj procesa obvladovanja tveganja (ISO 18562-1:2017)

General Information

• Status: Withdrawn
• Publication Date: 18-Feb-2020
• Withdrawal Date: 13-Apr-2025
• ICS: 11.040.10 - Anaesthetic, respiratory and reanimation equipment
• Technical Committee: CEN/TC 215 - Respiratory and anaesthetic equipment
• Drafting Committee: CEN/TC 215/WG 2 - Lung ventilators
• Current Stage: 9960 - Withdrawal effective - Withdrawal
• Start Date: 23-Oct-2024
• Completion Date: 14-Apr-2025
• Ref Project: SIST EN ISO 18562-1:2020 - Biocompatibility evaluation of breathing gas pathways in healthcare applications - Part 1: Evaluation and testing within a risk management process (ISO 18562-1:2017)

Relations

• Replaced By: EN ISO 18562-1:2024 - Biocompatibility evaluation of breathing gas pathways in healthcare applications - Part 1: Evaluation and testing within a risk management process (ISO 18562-1:2024)
• Effective Date: 18-Jan-2023

Standards Content (Sample)

SLOVENSKI STANDARD
01-april-2020
Ovrednotenje biokompatibilnosti vdihanega plina za uporabo v zdravstvu - 1. del:
Ovrednotenje in preskušanje znotraj procesa obvladovanja tveganja (ISO 18562-
1:2017)
Biocompatibility evaluation of breathing gas pathways in healthcare applications - Part 1:
Evaluation and testing within a risk management process (ISO 18562-1:2017)
Beurteilung der Biokompatibilität der Atemgaswege bei medizinischen Anwendungen -
Teil 1: Beurteilung und Prüfung innerhalb eines Risikomanagement-Prozesses (ISO
18562-1:2017)
Évaluation de la biocompatibilité des voies de gaz respiratoires dans les applications de
soins de santé - Partie 1: Évaluation et essais au sein d'un processus de gestion du
risque (ISO 18562-1:2017)
Ta slovenski standard je istoveten z: EN ISO 18562-1:2020
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 18562-1
EUROPEAN STANDARD
NORME EUROPÉENNE
February 2020
EUROPÄISCHE NORM
ICS 11.040.10
English Version
Biocompatibility evaluation of breathing gas pathways in
healthcare applications - Part 1: Evaluation and testing
within a risk management process (ISO 18562-1:2017)
Évaluation de la biocompatibilité des voies de gaz Beurteilung der Biokompatibilität der Atemgaswege
respiratoires dans les applications de soins de santé - bei medizinischen Anwendungen - Teil 1: Beurteilung
Partie 1: Évaluation et essais au sein d'un processus de und Prüfung innerhalb eines Risikomanagement-
gestion du risque (ISO 18562-1:2017) Prozesses (ISO 18562-1:2017)
This European Standard was approved by CEN on 11 November 2019.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this
European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references
concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN
member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by
translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management
Centre has the same status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,
Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2020 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 18562-1:2020 E
worldwide for CEN national Members.

Contents Page
European foreword . 3

European foreword
The text of ISO 18562-1:2017 has been prepared by Technical Committee ISO/TC 121 "Anaesthetic and
respiratory equipment” of the International Organization for Standardization (ISO) and has been taken
over as EN ISO 18562-1:2020 by 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 August 2020, and conflicting national standards shall
be withdrawn at the latest by August 2020.
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.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,
Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the
United Kingdom.
Endorsement notice
The text of ISO 18562-1:2017 has been approved by CEN as EN ISO 18562-1:2020 without any
modification.
INTERNATIONAL ISO
STANDARD 18562-1
First edition
2017-03
Biocompatibility evaluation of
breathing gas pathways in healthcare
applications —
Part 1:
Evaluation and testing within a risk
management process
Évaluation de la biocompatibilité des voies de gaz respiratoires dans
les applications de soins de santé —
Partie 1: Évaluation et essais au sein d’un processus de gestion du
risque
Reference number
ISO 18562-1:2017(E)
©
ISO 2017
ISO 18562-1:2017(E)
© ISO 2017, Published in Switzerland
All rights reserved. Unless otherwise specified, 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
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Tel. [phone]
Fax [phone]
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ii © ISO 2017 – All rights reserved

ISO 18562-1:2017(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 2
3 Terms and definitions . 2
4 General principles applying to biocompatibility evaluation of medical devices .6
4.1 General . 6
4.2 Type tests . 7
4.3 Biocompatibility hazard identification . 8
4.4 Extent of risk assessment . 8
4.5 Biocompatibility evaluation plan . 9
4.6 Selection of tests .10
4.7 Subsequent evaluation .10
5 Contamination of breathing gas from gas pathways .11
5.1 * Duration of use .11
5.2 Particulate matter (pm) emissions .13
5.3 Volatile organic compound (voc) emissions .13
5.4 Leachable substances in condensate .13
6 Adjustment for different patient groups .13
6.1 General considerations .13
6.2 Adjustment for body weight .13
6.3 * Deriving a permitted concentration from a tolerable exposure .14
7 * Deriving allowable limits .14
7.1 General process .14
7.2 For medical devices intended for limited exposure use (≤24 h) .15
7.3 For medical devices intended for prolonged exposure use (>24 h but <30 d) .16
7.4 For medical devices intended for permanent contact (≥30 d) .16
8 Risk benefit analysis .16
9 Assess the biocompatibility of the medical device .17
Annex A (informative) Rationale and guidance .18
Annex B (informative) Reference to the essential principles .20
Annex C (informative) Terminology — Alphabetized index of defined terms .21
Bibliography .23
ISO 18562-1:2017(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 on the voluntary nature of ISO standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO’s adherence to the
World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see the following
URL: w w w . i s o .org/ iso/ foreword .html.
The committee responsible for this document is ISO/TC 121, Anaesthetic and respiratory equipment,
Subcommittee SC 3, Lung ventilators and related equipment.
A list of all parts in the ISO 18562 series can be found on the ISO website.
iv © ISO 2017 – All rights reserved

ISO 18562-1:2017(E)
Introduction
This document represents the application of the best-known science, in order to improve patient
safety, by addressing the risk of potentially hazardous substances being conveyed to the patient by
the gas stream.
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 sufficiently address the biological evaluation of the gas
pathways of medical devices.
Before this document was developed, some authorities having jurisdiction interpreted the
ISO 10993-1:2009, Table A.1 to mean that materials in the gas pathway form “indirect contact” with
the patient, and should be subjected to tests equivalent to those required for tissue contact parts of
medical devices. This interpretation can lead to tests with questionable benefit and also to possible
hazards not being detected.
ISO 10993-1:2009 states that it is not intended to provide a rigid set of test methods as this might result
in an unnecessary constraint on the development and use of novel medical devices. ISO 10993-1:2009
also states where a particular application warrants it, experts in the product or in the area of application
concerned can choose to establish specific tests and criteria, described in a product-specific vertical
standard. This new series of standards is intended to address the specific needs for the evaluation of
gas pathways that are not adequately covered by ISO 10993-1:2009.
This document provides a guide to the development of a biological evaluation plan that minimizes
the number and exposure of test animals by giving preference to chemical constituent testing and
in vitro models.
The initial version of this series of standards was intended to cover only the most commonly found
potentially harmful substances. It was felt that it was best to get a functioning document published
that would test for the bulk of the currently known substances of interest. With the use of the ttc
(threshold of toxicological concern) approach, this document has the potential to be used
to assess the safety of essentially any compound released from the gas pathways of respiratory
medical devices, with very few exceptions (e.g. PCBs, dioxins), and not just the most commonly found
potentially harmful substances. Later amendments and additional parts are planned to explicitly cover
less common substances.
In this document, the following print types are used:
— requirements and definitions: roman type;
— test specifications: italic type;
— informative material appearing outside of tables, such as notes, examples and references: in smaller
type. Normative text of tables is also in a smaller type;
— terms defined in Clause 3 of this document or as noted: small capitals.
In this document, the conjunctive “or” is used as an “inclusive or” so a statement is true if any
combination of the conditions is true.
The verbal forms used in this document conform to usage described in Annex H of the ISO/IEC
Directives, Part 2. For the purposes of this document, the auxiliary verb:
— “shall” means that compliance with a requirement or a test is mandatory for compliance with this
document;
ISO 18562-1:2017(E)
— “should” means that compliance with a requirement or a test is recommended but is not mandatory
for compliance with this document;
— “may” is used to describe a permissible way to achieve compliance with a requirement or test.
An asterisk (*) as the first character of a title or at the beginning of a paragraph or table title indicates
that there is guidance or rationale related to that item in Annex A.
The attention of Member Bodies is drawn to the fact that equipment manufacturers and testing
organizations may need a transitional period following publication of a new, amended or revised ISO
or IEC publication in which to make products in accordance with the new requirements and to equip
themselves for conducting new or revised tests. It is the recommendation of the committee that the
content of this publication be adopted for implementation nationally not earlier than 3 years from
the date of publication for equipment newly designed and not earlier than 5 years from the date of
publication for equipment already in production.
vi © ISO 2017 – All rights reserved

INTERNATIONAL STANDARD ISO 18562-1:2017(E)
Biocompatibility evaluation of breathing gas pathways in
healthcare applications —
Part 1:
Evaluation and testing within a risk management process
1 Scope
This document specifies:
— the general principles governing the biological evaluation within a risk management process of
the 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 general categorization of gas pathways based on the nature and duration of their contact with
the gas stream;
— the evaluation of existing relevant data from all sources;
— the identification of gaps in the available data set on the basis of a risk analysis;
— the identification of additional data sets necessary to analyse the biological safety of the gas
pathway;
— the assessment of the biological safety of the gas pathway.
This document covers general principles regarding biocompatibility assessment of medical device
materials, which make up the gas pathway, but does not cover biological hazards arising from any
mechanical failure, unless the failure introduces a toxicity risk (e.g. by generating particulates). The
other parts of ISO 18562 cover specific tests that address potentially hazardous substances that are
added to the respirable gas stream and establish acceptance criteria for these substances.
This document addresses potential contamination of the gas stream arising from the gas pathways
within the medical device, which might then be conducted to the patient.
This document applies over the expected service life of the medical device in normal use and takes
into account the effects of any intended processing or reprocessing.
This document does not address biological evaluation of the surfaces of medical devices that are in 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 equipment, oxygen concentrators, nebulizers, low-pressure hose
assemblies, humidifiers, heat and moisture exchangers, respiratory gas monitors, respiration monitors,
masks, mouth pieces, resuscitators, breathing tubes, breathing system filters and Y-pieces as well as
any breathing accessories intended to be used with such medical 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.
ISO 18562-1:2017(E)
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 is not addressed by ISO 18562
(all parts).
Future parts might be added to address other relevant aspects of biological testing including additional
contamination that might arise from the gas pathway because of the presence of drugs and anaesthetic
agents added to the gas stream.
NOTE 1 Some authorities having jurisdiction require evaluation of these risks as part of a biological
evaluation.
NOTE 2 This document has been prepared to address the relevant essential principles of safety and
performance as indicated in Annex B.
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 7396-1:2016, Medical gas pipeline systems — Part 1: Pipeline systems for compressed medical gases
and vacuum
ISO 10993-1:2009, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
ISO 10993-17:2002, Biological evaluation of medical devices — Part 17: Establishment of allowable limits
for leachable substances
ISO 14971:2007, Medical devices — Application of risk management to medical devices
ISO 18562-2, Biocompatibility evaluation of breathing gas pathways in healthcare applications — Part 2:
Tests for emissions of particulate matter
ISO 18562-3, Biocompatibility evaluation of breathing gas pathways in healthcare applications — Part 3:
Tests for emissions of volatile organic compounds (VOCs)
ISO 18562-4, Biocompatibility evaluation of breathing gas pathways in healthcare applications — Part 4:
Tests for leachables in condensate
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 7396-1, ISO 14971 and the
following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— IEC Electropedia: available at http:// www .electropedia .org/
— ISO Online browsing platform: available at http:// www .iso .org/ obp
NOTE For convenience, an alphabetized index of all defined terms and their sources used in this document is
given in Annex C.
3.1
accessory
additional part for use with a medical device in order to:
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ISO 18562-1:2017(E)
— achieve the intended use,
— adapt it to some special use,
— facilitate its use,
— enhance its performance, or
— enable its function to be integrated with those of other medical devices
[SOURCE: IEC 60601-1:2005, 3.3, modified — substituted “medical device” for “equipment”]
3.2
biocompatibility
ability to be in contact with a living system without producing an unacceptable adverse effect
Note 1 to entry: Medical devices may produce some level of adverse effect, but that level may be determined to
be acceptable when considering the benefits provided by the medical device.
3.3
expected service life
maximum period of useful life as defined by the manufacturer
[SOURCE: IEC 60601-1:2005+AMD1: 2012, 3.28]
3.4
formulation
base polymer or alloy, including additives, colours, etc. used to establish a property or the stability of
the material
Note 1 to entry: This does not include processing aids, mould release agents, residual contaminants, or other
manufacturing aids that are not intended to be a part of the material.
Note 2 to entry: The term “chemical composition” is commonly used as a synonym for formulation.
[SOURCE: US FDA 510(k) Memorandum #K97-1]
3.5
gas pathway
interior surfaces, over which gases or liquids that can be inspired, in a medical device bounded by
the ports through which gases or liquids enter and leave the medical device including the patient
interface or the interior surfaces of enclosures that are in contact with gases or liquids that can be
inspired
Note 1 to entry: patient contact surfaces such as the outer surfaces of a tracheal tube or the cushion of a mask
are evaluated according to the ISO 10993 series.
EXAMPLE 1 The ventilator breathing system, inlet filter, gas mixer, blower and internal piping.
EXAMPLE 2 Enclosed chamber of an incubator including the mattress or the inner surface of an oxygen hood.
EXAMPLE 3 The inner surfaces of breathing tubes, tracheal tubes or masks and mouthpieces.
3.6
leachable substance
chemical removed from a medical device by the action of water, other liquids or other gases (e.g.
anaesthetic agents or inhalational drugs) related to the use of the medical device
EXAMPLE Additives, sterilant residues, process residues, degradation products, solvents, plasticizers,
lubricants, catalysts, stabilizers, anti-oxidants, colouring agents, fillers and monomers, among others.
[SOURCE: ISO 10993-17:2002, 3.10, modified — added “or other gases (e.g. anaesthetic agents or
inhalational drugs)”]
ISO 18562-1:2017(E)
3.7
medical device
instrument, apparatus, implement, machine, appliance, implant, reagent for in vitro use, software,
material or other similar or related article, intended by the manufacturer to be used, alone or in
combination, for human beings for one or more of the following specific purpose(s) of:
— diagnosis, prevention, monitoring, treatment or alleviation of disease;
— diagnosis, monitoring, treatment, alleviation of or compensation for an injury;
— investigation, replacement, modification, or support of the anatomy or of a physiological process;
— supporting or sustaining life;
— control of conception;
— disinfection of medical devices;
— providing information by means of in vitro examination of specimens derived from the human body;
and does not achieve its primary intended action by pharmacological, immunological or metabolic
means, in or on the human body, but which may be assisted in its function by such means
Note 1 to entry: Products which may be considered to be medical devices in some jurisdictions but not in others
include:
— disinfection substances;
— aids for persons with disabilities;
— devices incorporating animal and/or human tissues;
— devices for in vitro fertilization or assisted reproduction technologies.
[SOURCE: ISO 13485:2016, 3.11]
3.8
normal condition
condition in which all means provided for protection against hazards are intact
[SOURCE: IEC 60601-1:2005, 3.70]
3.9
normal use
operation, including routine inspection and adjustments by any user, and stand-by, according to the
instructions for use
Note 1 to entry: Normal use should not be confused with intended use. While both include the concept of use as
intended by the manufacturer, intended use focuses on the medical purpose while normal use incorporates
not only the medical purpose but maintenance, service, transport, etc. as well.
[SOURCE: IEC 60601-1:2005+AMD1: 2012, 3.97, modified — replaced “operator” with “user”]
3.10
particulate matter
pm
particulates
solid particles suspended in a gas
3.11
patient
living human undergoing a medical, surgical, or dental procedure
[SOURCE: IEC 60601-1:2005+AMD1: 2012, 3.76, modified — removed reference to animal]
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ISO 18562-1:2017(E)
3.12
threshold of toxicological concern
ttc
level of exposure for all chemicals, known or unknown, below which it is considered there is no
appreciable risk to human health
Note 1 to entry: A ttc is used as an acceptable value for a te for an unknown or insufficiently characterized
compound.
3.13
tolerable exposure
te
total amount of a substance (in units of µg/d) that a patient can be exposed to per 24 h period that is
considered to be without appreciable harm to health
Note 1 to entry: Te is also referred to as “allowed dose to patient”. This amount is specific to a particular patient
or patient group of a given body weight.
Note 2 to entry: Te is calculated by multiplying tolerable intake by the body mass.
3.14
tolerable intake
ti
tolerable intake level
til
total amount of a substance per kilogram of body weight (in units of µg/kg body weight/d) that a
patient can be exposed to per 24 h period that is considered to be without appreciable harm to health
Note 1 to entry: This amount is applicable for all patient groups.
3.15
type test
test on a representative sample of the medical device with the objective of determining if the medical
device, as designed and manufactured, can meet the requirements of this document
Note 1 to entry: If the final medical device is not used for the assessments, all differences between the
“representative sample” and the final medical device need to be described and a justification provided for why
the differences do not affect the outcome of the testing.
[SOURCE: IEC 60601-1:2005, 3.135, modified — substituted “medical device” for “me equipment” and
added Note 1]
3.16
volatile organic compound
voc
organic compound whose boiling point is in the range of 50 °C to 260 °C
Note 1 to entry: There are many varied definitions of voc. For the purposes of this document, a voc is a compound
that has a boiling point in the range of 50 °C to 260 °C, at a standard atmospheric pressure of 101,3 kPa.
Note 2 to entry: Boiling points of some compounds are difficult or impossible to determine because they
decompose before they boil at atmospheric pressure.
Note 3 to entry: Compounds still exert a vapour pressure, and so could enter the breathing gas, at temperatures
lower than their boiling point.
Note 4 to entry: voc does not include very volatile organic compounds (vvocs) nor semi-volatile organic
compounds (SVOCs). Additional parts of this document might be developed to address these substances in
the future. Some authorities having jurisdiction require evaluation of these risks as part of a biological
evaluation.
ISO 18562-1:2017(E)
3.17
very volatile organic compound
vvoc
organic compound whose boiling point is in the range of 0 °C to 50 °C
Note 1 to entry: Boiling points of some compounds are difficult or impossible to determine because they
decompose before they boil at atmospheric pressure.
4 General principles applying to biocompatibility evaluation of medical devices
4.1 General
The biocompatibility evaluation of any material or medical device, part or accessory intended for
use with patients shall form part of a structured biocompatibility evaluation programme within
a risk management process. The biocompatibility evaluation shall be planned, carried out and
documented by knowledgeable and experienced professionals. Figure 1 illustrates this process.
The evaluation programme shall include documented, informed decisions that assess the
advantages/disadvantages and relevance of:
— the physical and chemical characteristics of the various candidate materials over the expected
service life of the medical device;
NOTE Where this information is already documented within the risk management file for the
medical device, it can be included by reference.
— any history of human exposure data;
— any existing toxicology and other biocompatibility safety data on product and component
materials, breakdown products and metabolites.
All medical devices should be evaluated for biocompatibility, but evaluation does not necessarily
imply testing everything. Depending on the final formulation, manufacturing or application, an
evaluation may result in the conclusion that no testing or no additional testing is needed.
EXAMPLE The medical device has a demonstrable similarity in a specified function and physical form, has
identical formulation, contains no additional chemicals, uses the same manufacturing processes, so that it is
equivalent to a medical device, part or accessory that has already been evaluated.
Check compliance by inspection of the risk management plan and risk management file.
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Figure 1 — Risk management process for biological evaluation of gas pathways
4.2 Type tests
The tests described in this document are type tests. Type tests are performed on the final medical
device, a component of the medical device or a representative sample of the medical device, part
or accessory being evaluated. If representative samples are used (i.e. manufactured and processed
by equivalent methods), consideration should be given to whether or not the differences between
the representative sample and the final medical device or component could affect the results of the
test. Testing of representative samples (manufactured and processed by equivalent methods) instead
of the final medical device should be supported by a description of any differences between the
ISO 18562-1:2017(E)
representative sample and the final medical device, and a detailed rationale for why each difference is
not expected to impact the biocompatibility of the final medical device.
NOTE Some authorities having jurisdiction evaluate these differences and rationales.
4.3 Biocompatibility hazard identification
Identify all the possible biocompatibility-related hazards that might reach the patient via the gas
pathways during the use of the medical device.
All known possible biocompatibility-related hazards shall be taken into account for every material
and final medical device, part or accessory. This does not imply that testing for all possible hazards
is necessary or practical. ISO 10993-1:2009, Clause 5 and Clause 6 have additional requirements for
additional types and durations of patient exposure.
EXAMPLE For a medical device (such as a mask) that has direct patient contact in addition to gas pathway
contact, assessment for compliance to both ISO 18562-1 and ISO 10993-1 can be required.
In the selection of materials to be used in gas pathway manufacture, the first consideration should
be fitness for purpose with regard to characteristics and properties of the material, which includes
physical, mechanical, chemical and toxicological properties.
Materials used to manufacture the components in the gas pathways should be suitable for the
intended use, and use materials with demonstrable history of safe use in the intended or comparable
application wherever possible.
The following shall be taken into account for their relevance to the overall biological evaluation of the
gas pathway:
— the material(s) of manufacture;
— intended additives, process contaminants and residues;
— substances released in normal use;
— degradation products from normal use that might pass into the patient via the gas pathways;
[1] [2] [3]
NOTE 1 ISO 10993-9 contains requirements for general principles and ISO 10993-13 , ISO 10993-14
[4]
and ISO 10993-15 contain requirements for degradation products from polymers, ceramics and
metals, respectively. If testing for degradation using dry heat only, then ISO 10993-13, ISO 10993-14 and
ISO 10993-15 need not apply.
NOTE 2 Normal use can include use with heated and humidified breathing gas. Tests are done on the
“worst case” configuration. This can mean testing with and without heat and humidification to establish the
worst case.
— other components and their interactions in the final medical device, part or accessory;
— the performance and characteristics of the final medical device, part or accessory;
— physical characteristics of the final medical device, part or accessory including, but not limited to,
porosity, particle size and shape;
— the effects of any hygienic processing steps required before use or re-use, if applicable.
Check compliance by inspection of the risk management plan and risk management file.
4.4 Extent of risk assessment
An analysis shall be made of the hazards identified in 4.3, and the risk that the hazard poses to the
patient determined. The results shall be documented.
NOTE 1 ISO 10993-1:2009, Figure 1 is a graphical representation of the risk assessment process.
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ISO 18562-1:2017(E)
The rigour necessary in the biological evaluation is principally determined by the duration and
frequency of the exposure and the hazards identified for the medical device. The information needed
to support a biological evaluation, including any test data, shall take into account the physical and
chemical characteristics of the materials, the electromechanical nature of the medical device, as well
as the frequency, duration and conditions of exposure of the patient to the gas from the gas pathway.
This enables the categorization of uses to facilitate the selection of appropriate tests, if required.
NOTE 2 ISO 10993-1:2009, Clause5 contains additional requirements.
4.5 Biocompatibility evaluation plan
Having identified the possible biocompatibility hazards and determined the risks that they might
pose to the patient, a biocompatibility evaluation plan shall be created.
This plan shall detail what is currently known about the material formulation, additives and process
aids used in the manufacture of the gas pathways of the medical device, and therefore identify gaps
in knowledge that shall be filled by further work.
If a potential hazard has been identified, but the risk it poses to the patient can be shown to be
negligible (for example, the dose the patient receives is less than the tolerable exposure), then no
further work on the hazard is required. The decision shall be documented.
If a potential hazard has been identified, but the risk it poses to the patient is not negligible, or the
risk is unknown, then further work to characterize or mitigate the hazard is required. This step may
involve referring to previous similar medical devices and manufacturing methods, accessing reliable
information in the public domain, or performing tests to gather the data.
All medical devices should be evaluated for biocompatibility, but evaluation does not automatically
imply testing. Depending on the final formulation, manufacturing and application, an evaluation may
result in the conclusion that no testing or no additional testing is needed.
EXAMPLE The medical device has a demonstrable similarity in a specified function and physical form, has
identical formulation, contains no additional chemicals, uses the same manufacturing processes, so that it is
equivalent to a medical device, part or accessory that has already been evaluated.
To reduce animal testing for gas pathways that can contact liquids, identification of material chemical
constituents and consideration of chemical characterization shall be undertaken, and only if results
show the presence of substances, which do not have sufficient toxicological data to allow risk
assessment, should any biological testing be considered.
NOTE 1 Some local effects including cytotoxicity, irritation, and sensitization might not be adequately
assessed using a chemical characterization/risk assessment approach. As a result, it can be necessary to
conduct biological testing to assess these end points. Systemic effects including acute, subacute, subchronic and
chronic toxicity, reproductive and developmental toxicity, genotoxicity and carcinogenicity can often be assessed
using a chemical characterization/risk assessment approach.
An evaluation of particulate matter shall be included in the biocompatibility evaluation.
Test results cannot guarantee freedom from potential biological hazards. Thus, biological
investigations shall be followed by careful observations for unexpected adverse reactions or events in
humans during use of the final medical device, part or accessory.
NOTE 2 The range of possible biological hazards is wide and can include short-term effects, as well as long-
term or specific toxic effects.
The biological evaluation of a gas pathway shall take into account the nature and mobility of the
chemical constituents in the materials used to manufacture the medical device, part or accessory and
ISO 18562-1:2017(E)
other information, other non-clinical tests, clinical studies, and post-market experience for an overall
assessment.
NOTE 3 This series does not currently address biocompatibility hazards associated with the following
substances being added to the respirable gas stream. Nonetheless, when applicable, some authorities having
jurisdiction require the manufacturer to evaluate the following:
— semi-volatile organic compounds and vvocs;
— ozone, for gas pathways in contact with active electromechanical or electrostatic parts in normal condition;
— CO and CO , for gas pathways where inorganic gases are generated or concentrated;
— leachables, for gas pathways in contact with anaesthetic agents where the gas can be inspired in normal
condition;
— leachables, for gas pathways in contact with substances intended to be delivered via the respiratory tract
(e.g. inhalational drugs).
4.6 Selection of tests
The results of the biocompatibility evaluation plan might indicate that further information is required.
If this
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