SIST EN ISO 22442-1:2016
(Main)Medical devices utilizing animal tissues and their derivatives - Part 1: Application of risk management (ISO 22442-1:2015)
Medical devices utilizing animal tissues and their derivatives - Part 1: Application of risk management (ISO 22442-1:2015)
This part of ISO 22442 applies to medical devices other than in vitro diagnostic medical devices
manufactured utilizing materials of animal origin, which are non-viable or have been rendered nonviable.
It specifies, in conjunction with ISO 14971, a procedure to identify the hazards and hazardous
situations associated with such devices, to estimate and evaluate the resulting risks, to control these
risks, and to monitor the effectiveness of that control. Furthermore, it outlines the decision process for
the residual risk acceptability, taking into account the balance of residual risk, as defined in ISO 14971,
and expected medical benefit as compared to available alternatives. This part of ISO 22442 is intended
to provide requirements and guidance on risk management related to the hazards typical of medical
devices manufactured utilizing animal tissues or derivatives such as
a) contamination by bacteria, moulds or yeasts;
b) contamination by viruses;
c) contamination by agents causing Transmissible Spongiform Encephalopathies (TSE);
d) material responsible for undesired pyrogenic, immunological or toxicological reactions.
For parasites and other unclassified pathogenic entities, similar principles can apply.
This part of ISO 22442 does not stipulate levels of acceptability which, because they are determined
by a multiplicity of factors, cannot be set down in such an International Standard except for some
particular derivatives mentioned in Annex C. Annex C stipulates levels of TSE risk acceptability for
tallow derivatives, animal charcoal, milk and milk derivatives, wool derivatives and amino acids.
This part of ISO 22442 does not specify a quality management system for the control of all stages of
production of medical devices.
This part of ISO 22442 does not cover the utilization of human tissues in medical devices.
NOTE 1 It is not a requirement of this part of ISO 22442 to have a full quality management system during
manufacture. However, attention is drawn to International Standards for quality management systems
(see ISO 13485) that control all stages of production or reprocessing of medical devices.
NOTE 2 For guidance on the application of this part of ISO 22442, see Annex A.
Tierische Gewebe und deren Derivate, die zur Herstellung von Medizinprodukten eingesetzt werden - Teil 1: Anwendung des Risikomanagements (ISO 22442-1:2015)
Dieser Teil von ISO 22442 bezieht sich auf Medizinprodukte, mit Ausnahme von in-vitro-Diagnostika, hergestellt unter Verwendung von Materialien tierischen Ursprungs, die nicht lebensfähig sind oder abgetötet wurden. Er ergibt in Verbindung mit ISO 14971 ein Verfahren zur Identifizierung der Gefahren und gefährlichen Situationen im Zusammenhang mit diesen Produkten, zur Abschätzung und Beurteilung der sich ergebenden Risiken, zur Kontrolle dieser Risiken und zur Überwachung der Wirksamkeit dieser Kontrolle. Zusätzlich umschreibt er den Entscheidungsprozess für die Annehmbarkeit des Restrisikos, indem das Restrisiko, wie in ISO 14971 definiert, abgewägt und der erwartete medizinische Nutzen, verglichen mit verfügbaren Alternativen, einander gegenübergestellt wird. Dieser Teil von ISO 22442 legt Anforderungen und Anleitungen für das Risikomanagement in Bezug auf typische Gefährdungen durch Medizinprodukte fest, die unter Verwendung tierischer Gewebe und deren Derivate hergestellt wurden, z. B.
a) Verunreinigungen durch Bakterien, Schimmelpilze oder Hefepilze;
b) Verunreinigungen durch Viren;
c) Verunreinigungen durch Erreger, die übertragbare spongiforme Enzephalopathie (en: Transmissible Spongiform Encephalopathy, TSE) hervorrufen;
d) für ungewünschte pyrogene, immunologische oder toxikologische Reaktionen verantwortliches Material.
Bei Parasiten und anderen nicht klassifizierten pathogenen Einheiten können ähnliche Prinzipien gelten.
Dieser Teil von ISO 22442 legt keine Anforderungen für die Akzeptanz fest, weil diese von einer Vielzahl von Faktoren bestimmt und in einer solchen Internationalen Norm nicht festgelegt werden können. Ausgenommen sind bestimmte Derivate, die in Anhang C erwähnt werden. Anhang C legt Grade für die Annehmbarkeit von TSE-Risiken bei Talg-Derivaten, Kohle aus tierischem Ausgangsmaterial, Milch und Milch-Derivaten, Derivaten von Wolle und Aminosäuren fest.
Dieser Teil von ISO 22442 legt kein Qualitätsmanagementsystem zur Kontrolle aller Produktionsschritte eines Medizinproduktes fest.
Dieser Teil von ISO 22442 gilt nicht für die Verwendung von menschlichen Geweben in Medizinprodukten.
ANMERKUNG 1 Es ist keine Anforderung dieses Teils von ISO 22442, ein vollständiges Qualitätsmanagementsystem für die Herstellung zu nutzen. Es wird jedoch auf Internationale Normen für Qualitätsmanagementsysteme (siehe ISO 13485) zur Kontrolle aller Schritte der Produktion und Wiederaufarbeitung von Medizinprodukten hingewiesen.
ANMERKUNG 2 Eine Anleitung zur Anwendung dieses Teils von ISO 22442 ist in Anhang A gegeben.
Dispositifs médicaux utilisant des tissus animaux et leurs dérivés - Partie 1: Application de la gestion des risques (ISO 22442-1:2015)
L'ISO 22442-1:2015 s'applique aux dispositifs médicaux autres que les dispositifs médicaux de diagnostic in vitro, dans la fabrication desquels entrent des matériaux d'origine animale non viables ou rendus non viables. Associée à l'ISO 14971, elle spécifie un mode opératoire permettant d'identifier les dangers et les situations dangereuses associés à de tels dispositifs, d'estimer et d'évaluer les risques qui en découlent, de maîtriser ces risques et de surveiller l'efficacité de cette maîtrise. En outre, elle décrit le processus décisionnel relatif à l'acceptabilité du risque résiduel, en tenant compte du rapport entre le risque résiduel, tel que défini dans l'ISO 14971, et le bénéfice médical escompté par rapport aux solutions de remplacement disponibles. L'ISO 22442-1:2015 est destinée à fournir des exigences et des lignes directrices pour la gestion des risques associée aux dangers typiques des dispositifs médicaux dans la fabrication desquels entrent des tissus ou des dérivés d'origine animale, notamment:
a) la contamination par des bactéries, des moisissures ou des levures;
b) la contamination par des virus;
c) la contamination par des agents responsables d'encéphalopathies spongiformes transmissibles (EST);
d) un matériau provoquant des réactions pyrogènes, immunologiques ou toxicologiques indésirables.
Medicinski pripomočki, ki uporabljajo živalska tkiva in njihove derivate - 1. del: Uporaba obvladovanja tveganja (ISO 22442-1:2015)
Ta del standarda ISO 22442 se uporablja za medicinske pripomočke, ki niso diagnostični medicinski pripomočki in vitro in so proizvedeni iz neživih ali odmrlih materialov živalskega izvora.
V povezavi s standardom ISO 14971 določa postopek za prepoznavanje tveganj in nevarnih razmer, povezanih s takšnimi pripomočki, za ocenjevanje in ovrednotenje nastalih tveganj ter njihovo obvladovanje, ter za nadzor učinkovitosti tega obvladovanja. Poleg tega opredeljuje postopek odločanja glede sprejemljivosti ostalih tveganj z upoštevanjem uravnoteženosti ostalega tveganja, ki je opredeljena v standardu ISO 14971, ter pričakovane medicinske koristi v primerjavi z razpoložljivimi alternativnimi možnostmi. Ta del standarda ISO 22442 podaja zahteve in smernice za obvladovanje tveganj, značilnih za medicinske pripomočke, proizvedene iz živalskih tkiv ali derivatov, kot so a) kontaminacija z bakterijami, plesnimi ali kvasovkami;
b) kontaminacija z virusi;
c) kontaminacija s povzročitelji, ki povzročajo prenosljive spongiformne encefalopatije (TSE);
d) material, ki povzroča neželene pirogene, imunološke ali toksikološke reakcije.
Za parazite in druge nerazvrščene patogene mikroorganizme je mogoče uporabiti podobna načela. Ta del standarda ISO 22442 ne predpisuje ravni sprejemljivosti, ki jih zaradi vplivanja množice dejavnikov v takšnem mednarodnem standardu ni mogoče opredeliti, razen za nekatere posamezne derivate, omenjene v dodatku C. Dodatek C predpisuje ravni sprejemljivosti tveganja prenosljive spongiformne encefalopatije za derivate iz loja, živalsko oglje, mleko in mlečne derivate, derivate iz volne ter aminokisline. Ta del standarda ISO 22442 ne določa sistema vodenja kakovosti za nadzor vseh faz proizvodnje medicinskih pripomočkov. Ta del standarda ISO 22442 ne zajema uporabe človeških tkiv v medicinskih pripomočkih.
OPOMBA 1: Ta del standarda ISO 22442 ne zahteva popolnega sistema vodenja kakovosti med proizvodnjo. Kljub temu so izpostavljeni mednarodni standardi za sisteme vodenja kakovosti (glejte ISO 13485), ki nadzirajo vse faze proizvodnje ali ponovne obdelave medicinskih pripomočkov.
OPOMBA 2: Za smernice o uporabi tega dela standarda ISO 22442 glejte dodatek A.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 22442-1:2016
01-februar-2016
1DGRPHãþD
SIST EN ISO 22442-1:2008
0HGLFLQVNLSULSRPRþNLNLXSRUDEOMDMRåLYDOVNDWNLYDLQQMLKRYHGHULYDWHGHO
8SRUDEDREYODGRYDQMDWYHJDQMD ,62
Medical devices utilizing animal tissues and their derivatives - Part 1: Application of risk
management (ISO 22442-1:2015)
Tierische Gewebe und deren Derivate, die zur Herstellung von Medizinprodukten
eingesetzt werden - Teil 1: Anwendung des Risikomanagements (ISO 22442-1:2015)
Dispositifs médicaux utilisant des tissus animaux et leurs dérivés - Partie 1: Application
de la gestion des risques (ISO 22442-1:2015)
Ta slovenski standard je istoveten z: EN ISO 22442-1:2015
ICS:
11.120.01 Farmacija na splošno Pharmaceutics in general
SIST EN ISO 22442-1:2016 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 22442-1:2016
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SIST EN ISO 22442-1:2016
EN ISO 22442-1
EUROPEAN STANDARD
NORME EUROPÉENNE
November 2015
EUROPÄISCHE NORM
ICS 11.100.99 Supersedes EN ISO 22442-1:2007
English Version
Medical devices utilizing animal tissues and their
derivatives - Part 1: Application of risk management (ISO
22442-1:2015)
Dispositifs médicaux utilisant des tissus animaux et Tierische Gewebe und deren Derivate, die zur
leurs dérivés - Partie 1: Application de la gestion des Herstellung von Medizinprodukten eingesetzt werden -
risques (ISO 22442-1:2015) Teil 1: Anwendung des Risikomanagements (ISO
22442-1:2015)
This European Standard was approved by CEN on 1 November 2015.
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, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, 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: Avenue Marnix 17, B-1000 Brussels
© 2015 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 22442-1:2015 E
worldwide for CEN national Members.
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SIST EN ISO 22442-1:2016
EN ISO 22442-1:2015 (E)
Contents Page
European foreword . 3
Relationship between this European Standard and the Essential Requirements of
EU Directive 93/42/EEC. 5
2
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SIST EN ISO 22442-1:2016
EN ISO 22442-1:2015 (E)
European foreword
This document (EN ISO 22442-1:2015) has been prepared by Technical Committee ISO/TC 194
"Biological evaluation of medical devices" in collaboration with Technical Committee CEN/TC 316
“Medical devices utilizing tissues” the secretariat of which is held by DIN.
This European Standard shall be given the status of a national standard, either by publication of an
identical text or by endorsement, at the latest by May 2016 and conflicting national standards shall be
withdrawn at the latest by May 2016.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent
rights.
This document supersedes EN ISO 22442-1:2007.
This document has been prepared under a mandate given to CEN by the European Commission and the
European Free Trade Association, and supports essential requirements of EU Directive(s).
For relationship with EU Directive, see informative Annex ZA, which is an integral part of this
document.
The following referenced documents are indispensable for the application of this document. For
undated references, the latest edition of the referenced document (including any amendments) applies.
For dated references, only the edition cited applies. However, for any use of this standard ‘within the
meaning of Annex ZA’, the user should always check that any referenced document has not been
superseded and that its relevant contents can still be considered the generally acknowledged state-of-
art.
When an IEC or ISO standard is referred to in the ISO standard text, this shall be understood as a
normative reference to the corresponding EN standard, if available, and otherwise to the dated version
of the ISO or IEC standard, as listed below.
NOTE The way in which these referenced documents are cited in normative requirements determines the
extent (in whole or in part) to which they apply.
3
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SIST EN ISO 22442-1:2016
EN ISO 22442-1:2015 (E)
Table 1 – Correlation between normative references and dated EN and ISO standards
Normative references Equivalent dated standard
as listed in Clause 2 of the ISO
EN ISO
standard
ISO 10993-1 EN ISO 10993-1:2009 ISO 10993-1:2009
ISO 14971 ISO 14971:2012 ISO 14971:2007
ISO 22442-2 EN ISO 22442-2:2016 ISO 22442-2:2016
ISO 22442-3 EN ISO 22442-3:2007 ISO 22442-3:2007
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, Former Yugoslav Republic of Macedonia,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,
Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and the United Kingdom.
Endorsement notice
The text of ISO 22442-1:2015 has been approved by CEN as EN ISO 22442-1:2015 without any
modification.
4
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SIST EN ISO 22442-1:2016
EN ISO 22442-1:2015 (E)
Annex ZA
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC
This European Standard has been prepared under a mandate given to CEN by the European
Commission and the European Free Trade Association to provide a means of conforming to the
Essential Requirements of Directive 93/42/EEC, concerning medical devices, as amended by
Commission Regulation (EU) No722/2012 in relation to detailed specifications regarding requirements
for medical devices utilizing tissues of animal origin.
Once this standard is cited in the Official Journal of the European Union under that Directive and has
been implemented as a national standard in at least one Member State, 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 Essential Requirements of that Directive and
associated EFTA Regulations.
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 Directive 93/42/EEC, as amended by
2007/47/EC. This means that risks have to be reduced ‘as far as possible’, ‘to a minimum’, ‘to the lowest
possible level’, ‘minimized’ or ‘removed’, according to the wording of the corresponding essential
requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with
essential requirements 1, 2, 5, 6, 7, 8, 9, 11 and 12 of the Directive.
NOTE 3 This Annex ZA is based on normative references according to the table of references in the
European foreword, replacing the references in the core text.
NOTE 4 When an Essential Requirement does not appear in Table ZA.1, it means that it is not addressed
by this European Standard.
5
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SIST EN ISO 22442-1:2016
EN ISO 22442-1:2015 (E)
Table ZA.1 — Correspondence between this International Standard and Directive 93/42/EEC as
amended by Commission Regulation (EU) No 722/2012
Essential Requirements
(ERs) of Directive
93/42/EEC as amended
Clause(s)/subclause(s) of this Qualifying
by Commission
European Standard remarks/notes
Regulation (EU) No
722/2012
4.1, 4.2, 4.3, 4.4, 4.5, 4.6 and
7.1
Annex C
4.1, 4.2, 4.3, 4.4, 4.5, 4.6 and
7.2
Annex C
4.1, 4.2, 4.3, 4.4, 4.5, 4.6 and
8.1
Annex C
4.1, 4.2, 4.3, 4.4, 4.5, 4.6 and
8.2
Annex C
Annexes C and D Annex I of Commission Annexes C and D are
Regulation (EU) No dedicated to TSE risk,
722/2012 but 4.1, 4.2, 4.3, 4.4 are
also relevant.
WARNING — Other requirements and other EU Directives may be applicable to the product(s)
falling within the scope of this standard.
6
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SIST EN ISO 22442-1:2016
INTERNATIONAL ISO
STANDARD 22442-1
Second edition
2015-11-01
Medical devices utilizing animal
tissues and their derivatives —
Part 1:
Application of risk management
Dispositifs médicaux utilisant des tissus animaux et leurs dérivés —
Partie 1: Application de la gestion des risques
Reference number
ISO 22442-1:2015(E)
©
ISO 2015
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SIST EN ISO 22442-1:2016
ISO 22442-1:2015(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2015, 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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Fax +41 22 749 09 47
copyright@iso.org
www.iso.org
ii © ISO 2015 – All rights reserved
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SIST EN ISO 22442-1:2016
ISO 22442-1:2015(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Risk management process . 3
4.1 General . 3
4.2 Risk analysis . 3
4.2.1 Identification of qualitative and quantitative characteristics related to the
safety of medical devices . 3
4.2.2 Identification of hazards and hazardous situations . 4
4.3 Risk evaluation . 5
4.4 Risk control . 5
4.4.1 General. 5
4.4.2 Risk control for viruses and TSE agents . 5
4.4.3 Risk control of other hazards . 5
4.4.4 Residual risk evaluation . 6
4.5 Evaluation of overall residual risk acceptability . 6
4.5.1 General. 6
4.5.2 Documentation . 6
4.6 Production and post-production information system . 7
Annex A (informative) Guidance on the application of this part of ISO 22442 .8
Annex B (informative) Graphical representation of part of the risk management process for
medical devices utilizing animal material . 9
Annex C (normative) Special requirements for some animal materials considering the risk
management for TSE agents .11
Annex D (informative) Information relevant to the management of TSE risk .16
Bibliography .25
© ISO 2015 – All rights reserved iii
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SIST EN ISO 22442-1:2016
ISO 22442-1:2015(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 meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical
Barriers to Trade (TBT), see the following URL: Foreword — Supplementary information.
The committee responsible for this document is ISO/TC 194, Biological and clinical evaluation of medical
devices, SC 1, Tissue product safety.
This second edition cancels and replaces the first edition (ISO 22442-1:2007), of which it constitutes a
minor revision.
ISO 22442 consists of the following parts, under the general title Medical devices utilizing animal tissues
and their derivatives:
— Part 1: Application of risk management
— Part 2: Controls on sourcing, collection and handling
— Part 3: Validation of the elimination and/or inactivation of viruses and transmissible spongiform
encephalopathy (TSE) agents
— Part 4: Principles for elimination and/or inactivation of transmissible spongiform encephalopathy (TSE)
agents and validation assays for those processes [Technical Report]
iv © ISO 2015 – All rights reserved
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SIST EN ISO 22442-1:2016
ISO 22442-1:2015(E)
Introduction
Certain medical devices utilize materials of animal origin.
Animal tissues and their derivatives are used in the design and manufacture of medical devices to
provide performance characteristics that have been chosen for advantages over non-animal based
materials. The range and quantities of materials of animal origin in medical devices vary. These
materials can comprise a major part of the device (e.g. bovine/porcine heart valves, bone substitutes
for use in dental or orthopaedic applications, haemostatic devices), can be a product coating or
impregnation (e.g. collagen, gelatine, heparin), or can be used in the device manufacturing process
(e.g. tallow derivatives such as oleates and stearates, foetal calf serum, enzymes, culture media).
ISO 14971 is a general standard which specifies a process for a manufacturer by identifying hazards
and hazardous situations associated with medical devices, including in vitro medical devices, to
estimate and evaluate the risks associated with those hazards, to control these risks and to monitor
the effectiveness of the control throughout the life cycle. This part of ISO 22442 provides additional
requirements and guidance for the evaluation of medical devices manufactured utilizing animal tissues
or derivatives which are non-viable or rendered non-viable.
This part of ISO 22442 is intended to cover medical devices including active implantable medical
devices such as implantable infusion pumps.
This part of ISO 22442 does not apply to in vitro diagnostic devices.
This part of ISO 22442 can only be used in combination with ISO 14971 and is not a “standalone” standard.
To show compliance with this part of ISO 22442, its specified requirements should be fulfilled. The
guidance given in the Notes and informative annexes is not normative and is not provided as a checklist
for auditors.
© ISO 2015 – All rights reserved v
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SIST EN ISO 22442-1:2016
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SIST EN ISO 22442-1:2016
INTERNATIONAL STANDARD ISO 22442-1:2015(E)
Medical devices utilizing animal tissues and their
derivatives —
Part 1:
Application of risk management
1 Scope
This part of ISO 22442 applies to medical devices other than in vitro diagnostic medical devices
manufactured utilizing materials of animal origin, which are non-viable or have been rendered non-
viable. It specifies, in conjunction with ISO 14971, a procedure to identify the hazards and hazardous
situations associated with such devices, to estimate and evaluate the resulting risks, to control these
risks, and to monitor the effectiveness of that control. Furthermore, it outlines the decision process for
the residual risk acceptability, taking into account the balance of residual risk, as defined in ISO 14971,
and expected medical benefit as compared to available alternatives. This part of ISO 22442 is intended
to provide requirements and guidance on risk management related to the hazards typical of medical
devices manufactured utilizing animal tissues or derivatives such as
a) contamination by bacteria, moulds or yeasts;
b) contamination by viruses;
c) contamination by agents causing Transmissible Spongiform Encephalopathies (TSE);
d) material responsible for undesired pyrogenic, immunological or toxicological reactions.
For parasites and other unclassified pathogenic entities, similar principles can apply.
This part of ISO 22442 does not stipulate levels of acceptability which, because they are determined
by a multiplicity of factors, cannot be set down in such an International Standard except for some
particular derivatives mentioned in Annex C. Annex C stipulates levels of TSE risk acceptability for
tallow derivatives, animal charcoal, milk and milk derivatives, wool derivatives and amino acids.
This part of ISO 22442 does not specify a quality management system for the control of all stages of
production of medical devices.
This part of ISO 22442 does not cover the utilization of human tissues in medical devices.
NOTE 1 It is not a requirement of this part of ISO 22442 to have a full quality management system during
manufacture. However, attention is drawn to International Standards for quality management systems
(see ISO 13485) that control all stages of production or reprocessing of medical devices.
NOTE 2 For guidance on the application of this part of ISO 22442, see Annex A.
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated
references, the latest edition of the referenced document (including any amendments) applies.
ISO 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
ISO 14971, Medical devices — Application of risk management to medical devices
© ISO 2015 – All rights reserved 1
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SIST EN ISO 22442-1:2016
ISO 22442-1:2015(E)
ISO 22442-2, Medical devices utilizing animal tissues and their derivatives — Part 2: Control on sourcing,
collection and handling
ISO 22442-3, Medical devices utilizing animal tissues and their derivatives — Part 3: Validation of the
elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 14971 and the following apply.
3.1
animal
any vertebrate or invertebrate [including amphibian, arthropod (e.g. crustacean), bird, coral, fish,
reptile, mollusc and mammal] excluding humans (Homo sapiens)
3.2
cell
smallest organized unit of any living form which is capable of independent existence and of replacement
of its own substance in a suitable environment
3.3
derivative
substance obtained from an animal material by a manufacturing process
EXAMPLE Hyaluronic acid, collagen, gelatine, monoclonal antibodies, chitosan, albumin.
3.4
elimination
removal process by which the number of transmissible agents is reduced
Note 1 to entry: The effectiveness of the process for the elimination of viruses and TSE agents should be expressed
mathematically in terms of a reduction factor (see C.2 and ISO 22442-3:2007, Annex F).
Note 2 to entry: Elimination aims to prevent infection or pathogenic reaction caused by transmissible agents.
3.5
inactivation
process by which the ability to cause infection or pathogenic reaction by a transmissible agent is reduced
Note 1 to entry: The effectiveness of the process for inactivation of viruses and TSE agents should be expressed
mathematically in terms of a reduction factor (see ISO 22442-3:2007, Annex F).
Note 2 to entry: Inactivation aims to prevent infection by, and replication of, transmissible agents.
3.6
medical device
any instrument, apparatus, implement, machine, appliance, implant, in vitro reagent or calibrator,
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 specific purpose(s):
— 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;
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— providing information for medical purposes by means of in vitro examination of specimens derived
from the human body;
and which does not achieve its primary intended action in or on the human body by pharmacological,
immunological or metabolic means, but which may be assisted in its intended function by such means
[40]
Note 1 to entry: This definition has been developed by the Global Harmonization Task Force (GHTF)
Note 2 to entry: This part of ISO 22442 does not apply to in vitro diagnostic devices.
3.7
non-viable
having no potential for metabolism or multiplication
3.8
technical agreement
binding contract between two or more parties that assigns responsibilities for technical requirements
3.9
tissue
organization of cells and/or extra-cellular constituents
3.10
transmissible agents
bacteria, mould, yeast, parasites, viruses, TSE agents and unclassified pathogenic entities
4 Risk management process
4.1 General
The manufacturer shall justify the use of animal material (including the choice of animal species and
tissues) based on the residual risk acceptability, taking into account the balance of residual risk and
expected medical benefit, as compared to available alternatives.
The requirements of ISO 14971 and 4.2 to 4.5 apply. Compliance with these requirements shall be
verified by inspection of the risk management file.
NOTE Further discussion of medical benefits and the risk/benefit analysis can be found in
ISO 14971:2007, D.6.
4.2 Risk analysis
4.2.1 Identification of qualitative and quantitative characteristics related to the safety of
medical devices
4.2.1.1 Does the device come into contact with the patient or other persons?
The quantity of material, the contact surface area and the type(s) of the material coming into contact
with body tissues or fluids as well as the type of body tissue or fluid it comes into contact with, shall be
addressed in the risk analysis. For TSE, guidance can be found in D.3.7.
NOTE 1 Medical devices such as orthopaedic shoes or components such as leather straps that come into
contact only with intact skin represent a low infective risk.
NOTE 2 The quantity of material coming into contact is one of the factors in producing biological effects.
See ISO 10993 (all parts) for the evaluation of such effects.
NOTE 3 The structure of animal tissues being processed can affect the inactivation and/or elimination of
transmissible agents, and the potential for retaining viable cells can be affected by the structure of the animal
tissues and derivatives being processed.
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4.2.1.2 What materials and/or components are incorporated in the medical device or are used with, or
are in contact with, the medical device?
The following factors shall be addressed, if applicable:
a) if viable animal materials are utilized in the manufacture of the medical device, verification that
the final medical device contains no viable animal material;
b) the intended use of any animal tissue or derivative;
c) geographical source, species, age and feeding (including use of animal-derived pro
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