SIST EN ISO 22442-1:2021
(Main)Medical devices utilizing animal tissues and their derivatives - Part 1: Application of risk management (ISO 22442-1:2020)
Medical devices utilizing animal tissues and their derivatives - Part 1: Application of risk management (ISO 22442-1:2020)
This document 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 document 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 document 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 document does not specify a quality management system for the control of all stages of production
of medical devices.
This document does not cover the utilization of human tissues in medical devices.
NOTE 1 It is not a requirement of this document 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 document, see Annex A.
Tierische Gewebe und deren Derivate, die zur Herstellung von Medizinprodukten eingesetzt werden - Teil 1: Anwendung des Risikomanagements (ISO 22442-1:2020)
Dieses Dokument bezieht sich auf Medizinprodukte, mit Ausnahme von in vitro Diagnostika, hergestellt unter Verwendung von Materialien tierischen Ursprungs, die nicht lebensfähig sind oder abgetötet wurden. Es legt 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 fest. Zusätzlich umschreibt es 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. Dieses Dokument soll Anforderungen und Anleitungen für das Risikomanagement in Bezug auf typische Gefährdungen durch Medizinprodukte bereitstellen, 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 Enzephalopathien (en: transmissible spongiform encephalopathies, TSE) hervorrufen;
d) für ungewünschte pyrogene, immunologische oder toxikologische Reaktionen verantwortliches Material.
Bei Parasiten und anderen nicht klassifizierten pathogenen Einheiten können ähnliche Prinzipien gelten.
Dieses Dokument 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.
Dieses Dokument legt kein Qualitätsmanagementsystem zur Kontrolle aller Produktionsschritte eines Medizinproduktes fest.
Dieses Dokument behandelt nicht die Verwendung von menschlichen Geweben in Medizinprodukten.
ANMERKUNG 1 Es ist keine Anforderung von diesem Dokument, 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 Dokuments ist in Anhang A gegeben.
Dispositifs médicaux utilisant des tissus animaux et leurs dérivés - Partie 1: Application de la gestion des risques (ISO 22442-1:2020)
Le présent document 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. Associé à l'ISO 14971, il 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, il 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. Le présent document est destiné à fournir des exigences et des préconisations 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.
Des principes similaires peuvent s'appliquer aux parasites et autres entités pathogènes non classées.
Le présent document ne stipule pas de niveaux d'acceptabilité qui, du fait qu'ils sont déterminés par de multiples facteurs, ne peuvent s'inscrire dans une telle Norme internationale, excepté pour certains dérivés particuliers mentionnés à l'Annexe C. L'Annexe C stipule des niveaux d'acceptabilité du risque d'EST pour les dérivés du suif, le noir animal, le lait et les dérivés du lait, les dérivés de la laine et les acides aminés.
Le présent document ne spécifie pas un système de management de la qualité permettant le contrôle de toutes les étapes de fabrication de dispositifs médicaux.
Le présent document ne couvre pas l'utilisation de tissus humains dans les dispositifs médicaux.
NOTE 1 Le présent document n'exige pas un système de management de la qualité complet lors de la fabrication. Toutefois, il est préférable de se référer aux Normes internationales relatives aux systèmes de management de la qualité (voir l'ISO 13485) qui contrôlent toutes les étapes de fabrication ou de retraitement des dispositifs médicaux.
NOTE 2 Voir l'Annexe A pour les préconisations relatives à l'application du présent document.
Medicinski pripomočki, ki uporabljajo živalska tkiva in njihove derivate - 1. del: Uporaba obvladovanja tveganja (ISO 22442-1:2020)
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 22442-1:2021
01-februar-2021
Nadomešča:
SIST EN ISO 22442-1:2016
Medicinski pripomočki, ki uporabljajo živalska tkiva in njihove derivate - 1. del:
Uporaba obvladovanja tveganja (ISO 22442-1:2020)
Medical devices utilizing animal tissues and their derivatives - Part 1: Application of risk
management (ISO 22442-1:2020)
Tierische Gewebe und deren Derivate, die zur Herstellung von Medizinprodukten
eingesetzt werden - Teil 1: Anwendung des Risikomanagements (ISO 22442-1:2020)
Dispositifs médicaux utilisant des tissus animaux et leurs dérivés - Partie 1: Application
de la gestion des risques (ISO 22442-1:2020)
Ta slovenski standard je istoveten z: EN ISO 22442-1:2020
ICS:
11.040.99 Druga medicinska oprema Other medical equipment
11.120.01 Farmacija na splošno Pharmaceutics in general
SIST EN ISO 22442-1:2021 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 22442-1:2021
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SIST EN ISO 22442-1:2021
EN ISO 22442-1
EUROPEAN STANDARD
NORME EUROPÉENNE
December 2020
EUROPÄISCHE NORM
ICS 11.100.20 Supersedes EN ISO 22442-1:2015
English Version
Medical devices utilizing animal tissues and their
derivatives - Part 1: Application of risk management (ISO
22442-1:2020)
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 22442-1:2020) Teil 1: Anwendung des Risikomanagements (ISO
22442-1:2020)
This European Standard was approved by CEN on 2 December 2020.
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 22442-1:2020 E
worldwide for CEN national Members.
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SIST EN ISO 22442-1:2021
EN ISO 22442-1:2020 (E)
Contents Page
European foreword . 3
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC as amended by Commission Regulation
(EU) No 722/2012 . 5
2
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SIST EN ISO 22442-1:2021
EN ISO 22442-1:2020 (E)
European foreword
This document (EN ISO 22442-1:2020) has been prepared by Technical Committee ISO/TC 194
"Biological and clinical evaluation of medical devices" in collaboration with Technical Committee
CEN/TC 206 “Biological and clinical evaluation of medical devices” 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 June 2021, and conflicting national standards shall be
withdrawn at the latest by June 2021.
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 22442-1:2015.
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 the relationship with EU Directive(s) 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 references documents are cited in normative requirements determines the
extent (in whole or in part) to which they apply.
Table — Correlations between normative references and dated EN and ISO standards
Normative references as listed in
Equivalent dated standard
Clause 2 of the ISO standard
EN ISO or IEC
ISO 10993-1 EN ISO 10993-1:2020 ISO 10993-1:2018
ISO 14971 EN ISO 14971:2019 ISO 14971:2019
ISO 22442-2:2020 EN ISO 22442-2:2020 ISO 22442-2:2020
ISO 22442-3:2007 EN ISO 22442-3:2007 ISO 22442-3:2007
3
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SIST EN ISO 22442-1:2021
EN ISO 22442-1:2020 (E)
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 22442-1:2020 has been approved by CEN as EN ISO 22442-1:2020 without any
modification.
4
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SIST EN ISO 22442-1:2021
EN ISO 22442-1:2020 (E)
Annex ZA
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC as amended by Commission
Regulation (EU) No 722/2012
This European Standard has been prepared under a Commission’s standardization request [M/023
concerning the development of European Standards related to medical devices] to provide one
voluntary means of conforming to essential requirements of Council Directive 93/42/EEC of 14 June
1993 concerning medical devices [OJ L 169].
Once this standard is cited in the Official Journal of the European Union under that Directive,
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, it means that it is not addressed by this
European Standard.
Table ZA.1 — Correspondence between this European Standard and Directive 93/42/EEC as
amended by Commission Regulation (EU) No 722/2012
Essential Requirements of Clause(s)/sub-clause(s) of this
Remarks/Notes
Directive 93/42/EEC EN
Covered for the choice of materials
based on animal tissues and their
derivatives with regards to toxicity
4.1, 4.2, 4.3, 4.4, 4.5, 4.6 and
7.1 first and second indents and compatibility with biological
Annex C
tissues, cells and body fluids. Not
covered for flammability. Not
covered for manufacture.
Covered for reducing risks to
patients resulting from
contaminants in materials used in
4.1, 4.2, 4.3, 4.4, 4.5, 4.6 and
medical devices based on animal
7.2
Annex C
tissues and their derivatives,
providing any resulting risks are
minimized. Not covered for
packing, manufacture, transport or
5
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SIST EN ISO 22442-1:2021
EN ISO 22442-1:2020 (E)
Essential Requirements of Clause(s)/sub-clause(s) of this
Remarks/Notes
Directive 93/42/EEC EN
storage.
Covered for reducing risks of
infection to patients resulting from
using materials in medical devices
8.1
4.1, 4.2, 4.3, 4.4, 4.5, 4.6 and based on animal tissues and their
Annex C derivatives, providing any resulting
First sentence only
risks are eliminated or reduced as
far as possible. Not covered for
manufacture.
Covered only for the veterinary
8.2
control of animals from which
4.2.1.2 d)
tissues and their derivatives have
first paragraph only
been obtained.
The requirements detailed in Section
1 of Annex I of Reg. 722/2012/EC
cover risk analysis and risk
management of medical devices
manufactured utilising non-viable
tissues, or derivatives thereof,
sourced from animals that are
Annex I of Commission
susceptible to TSEs, as defined in
4.1, 4.2, 4.3, 4.4, 4.5, 4.6 and
Regulation (EU) No 722/2012
Art. 1.2. The Regulation is therefore
Annex C
specific to TSE risks.
Annex C is dedicated to TSE risk,
but 4.1, 4.2, 4.3, 4.4, 4.5 and 4.6 are
relevant to the risk analysis and
risk management process required
by the Regulation.
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 products falling within the scope of
this standard.
6
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SIST EN ISO 22442-1:2021
INTERNATIONAL ISO
STANDARD 22442-1
Third edition
2020-09
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 22442-1:2020(E)
©
ISO 2020
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SIST EN ISO 22442-1:2021
ISO 22442-1:2020(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2020
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting
on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address
below or ISO’s member body in the country of the requester.
ISO copyright office
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Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2020 – All rights reserved
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SIST EN ISO 22442-1:2021
ISO 22442-1:2020(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 . 4
4.2.1 Identification of qualitative and quantitative characteristics related to the
safety of medical devices . 4
4.2.2 Identification of hazards and hazardous situations . 5
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 . 6
4.4.4 Residual risk evaluation . 6
4.5 Evaluation of overall residual risk acceptability . 7
4.5.1 General. 7
4.5.2 Documentation . 7
4.6 Production and post-production information system . 7
Annex A (informative) Guidance on the application of this document . 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 .17
Bibliography .24
© ISO 2020 – All rights reserved iii
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SIST EN ISO 22442-1:2021
ISO 22442-1:2020(E)
Foreword
ISO (the International Organization for Standardization) and IEC (the International Electrotechnical
Commission) form the specialized system for worldwide standardization. National bodies that
are members of ISO or IEC participate in the development of International Standards through
technical committees established by the respective organization to deal with particular fields of
technical activity. ISO and IEC technical committees collaborate in fields of mutual interest. Other
international organizations, governmental and non-governmental, in liaison with ISO and IEC, also
take part in the work.
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 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).
Attention is drawn to the possibility that some of the elements of this document may be the subject
of patent rights. ISO and IEC 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) or the IEC
list of patent declarations received (see http:// patents .iec .ch).
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 194, Biological and clinical evaluation of
medical devices, Subcommittee SC 1, Tissue product safety, in collaboration with the European Committee
for Standardization (CEN) Technical Committee CEN/TC 206, Biological and clinical evaluation of medical
devices, in accordance with the Agreement on technical cooperation between ISO and CEN (Vienna
Agreement).
This third edition cancels and replaces the second edition (ISO 22442-1:2015), which has been
technically revised.
The main changes compared to the previous edition are as follows:
— 4.4.2 has been updated;
— weblinks in C.2, bullet point 1, C.3.3 and C.4.4 have been updated;
— the weblink in D.3.3 has been updated;
— C.10 has been added;
— the bibliography has been updated.
A list of all parts in the ISO 22442 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 2020 – All rights reserved
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SIST EN ISO 22442-1:2021
ISO 22442-1:2020(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 document 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 document is intended to cover medical devices including active implantable medical devices such
as implantable infusion pumps.
This document does not apply to in vitro diagnostic devices.
This document can only be used in combination with ISO 14971 and is not a “stand-alone” standard.
NOTE Compliance to this document is shown by fulfilling its specified requirements. The guidance given in
the notes and the informative annexes is not normative and is not provided as a checklist for auditors.
© ISO 2020 – All rights reserved v
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SIST EN ISO 22442-1:2021
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SIST EN ISO 22442-1:2021
INTERNATIONAL STANDARD ISO 22442-1:2020(E)
Medical devices utilizing animal tissues and their
derivatives —
Part 1:
Application of risk management
1 Scope
This document 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 document 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 document 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 document does not specify a quality management system for the control of all stages of production
of medical devices.
This document does not cover the utilization of human tissues in medical devices.
NOTE 1 It is not a requirement of this document 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 document, 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 2020 – All rights reserved 1
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SIST EN ISO 22442-1:2021
ISO 22442-1:2020(E)
ISO 22442-2, Medical devices utilizing animal tissues and their derivatives — Part 2: Controls 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.
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
3.1
animal
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 (3.1) material which is involved directly in the manufacturing
process of the medical device or is part of the final medical device
EXAMPLE Hyaluronic acid, collagen, gelatine, monoclonal antibodies, chitosan and 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
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 specific medical purpose(s) of
— diagnosis, prevention, monitoring, treatment or alleviation of disease,
— diagnosis, monitoring, treatment, alleviation of or compensation for an injury,
2 © ISO 2020 – All rights reserved
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SIST EN ISO 22442-1:2021
ISO 22442-1:2020(E)
— 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 which 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 could be considered to be medical devices in some jurisdictions but not in others
include:
— disinfection substances;
— aids for persons with disabilities;
— devices incorporating animal (3.1) and/or human tissues;
— devices for in vitro fertilization or assisted reproduction technologies.
[SOURCE: ISO 13485:2003, 3.7]
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 (3.2) and/or extra-cellular
...
SLOVENSKI STANDARD
oSIST prEN ISO 22442-1:2018
01-november-2018
0HGLFLQVNLSULSRPRþNLNLXSRUDEOMDMRåLYDOVNDWNLYDLQQMLKRYHGHULYDWHGHO
8SRUDEDREYODGRYDQMDWYHJDQMD ,62',6
Medical devices utilizing animal tissues and their derivatives - Part 1: Application of risk
management (ISO/DIS 22442-1:2018)
Tierische Gewebe und deren Derivate, die zur Herstellung von Medizinprodukten
eingesetzt werden - Teil 1: Anwendung des Risikomanagements (ISO/DIS 22442-
1:2018)
Dispositifs médicaux utilisant des tissus animaux et leurs dérivés - Partie 1: Application
de la gestion des risques (ISO/DIS 22442-1:2018)
Ta slovenski standard je istoveten z: prEN ISO 22442-1
ICS:
11.040.99 Druga medicinska oprema Other medical equipment
11.100.99 Drugi standardi v zvezi z Other standards related to
laboratorijsko medicino laboratory medicine
oSIST prEN ISO 22442-1:2018 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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oSIST prEN ISO 22442-1:2018
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oSIST prEN ISO 22442-1:2018
DRAFT INTERNATIONAL STANDARD
ISO/DIS 22442-1
ISO/TC 194/SC 1 Secretariat: DIN
Voting begins on: Voting terminates on:
2018-08-09 2018-11-01
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
ICS: 11.100.20
THIS DOCUMENT IS A DRAFT CIRCULATED
This document is circulated as received from the committee secretariat.
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
IN ADDITION TO THEIR EVALUATION AS
ISO/CEN PARALLEL PROCESSING
BEING ACCEPTABLE FOR INDUSTRIAL,
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
STANDARDS MAY ON OCCASION HAVE TO
BE CONSIDERED IN THE LIGHT OF THEIR
POTENTIAL TO BECOME STANDARDS TO
WHICH REFERENCE MAY BE MADE IN
Reference number
NATIONAL REGULATIONS.
ISO/DIS 22442-1:2018(E)
RECIPIENTS OF THIS DRAFT ARE INVITED
TO SUBMIT, WITH THEIR COMMENTS,
NOTIFICATION OF ANY RELEVANT PATENT
RIGHTS OF WHICH THEY ARE AWARE AND TO
©
PROVIDE SUPPORTING DOCUMENTATION. ISO 2018
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oSIST prEN ISO 22442-1:2018
ISO/DIS 22442-1:2018(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2018
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting
on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address
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Published in Switzerland
ii © ISO 2018 – All rights reserved
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oSIST prEN ISO 22442-1:2018
ISO/DIS 22442-1:2018(E)
Contents Page
Foreword .v
Introduction .vi
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 . 7
4.6 Production and post-production information system .7
Annex A (informative) Guidance on the application of this document . 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
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC as amended by Commission Regulation
(EU) No 722/2012 .23
Bibliography .25
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oSIST prEN ISO 22442-1:2018
ISO/DIS 22442-1:2018(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 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: www .iso .org/iso/foreword .html.
This document was prepared by Technical Committee ISO/TC 194, Biological and clinical evaluation of
medical devices, Subcommittee SC 1, Tissue product safety.
This third edition cancels and replaces the second edition (EN ISO 22442-1:2015), which has undergone
minor revision.
The major changes are:
— Update of weblinks in C.2 Collagen, bullet point 1, C.3.3 Bones s the starting material and C.4.4
Stunning methods;
— Update of weblink in D.3.3 Geographical sourcing;
— Update of bibliography;
— Editorial revision.
A list of all parts in the ISO 22442- series can be found on the ISO website.
iv © ISO 2018 – All rights reserved
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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 document 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 document is intended to cover medical devices including active implantable medical devices such
as implantable infusion pumps.
This document does not apply to in vitro diagnostic devices.
This document can only be used in combination with ISO 14971 and is not a “stand-alone” Standard.
NOTE To show compliance with this document, 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 2018 – All rights reserved v
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oSIST prEN ISO 22442-1:2018
DRAFT INTERNATIONAL STANDARD ISO/DIS 22442-1:2018(E)
Medical devices utilizing animal tissues and their
derivatives —
Part 1:
Application of risk management
1 Scope
This document 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 document 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 document 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 document does not specify a quality management system for the control of all stages of production
of medical devices.
This document does not cover the utilization of human tissues in medical devices.
NOTE 1 It is not a requirement of this document 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 document 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
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ISO 22442-2:2015, Medical devices utilizing animal tissues and their derivatives — Part 2: Controls on
sourcing, collection and handling
ISO 22442-3:2007, 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.
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
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 which is directly involved in
the production of the medical device or which is a final part of the medical device
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;
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— 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 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 document 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 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.
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.
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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.
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 protein) of animals;
d) veterinary control, conditions under which the animal materials are recovered, potential for cross-
contamination;
e) the type and anatomical source of tissue;
f) the production process, particularly if it uses materials pooled from more than one animal;
g) the nature of material utilized in the medical device, (e.g. intact tissue, highly purified derivative);
h) the method of utilization or incorporation into the medical device.
In the case of medical devices utilizing several relevant constituents (e.g. from various species, origin
or tissues) or several similar types of constituents produced using different methods, each individual
constituent should be analysed separately.
4.2.1.3 Is the device supplied sterile or intended to be sterilized by the user or are other
microbiological controls applicable?
Given the biological nature of animal tissues or derivatives, variations in the bioburden of bacteria,
mould and yeast of the animal material shall be estimated.
NOTE See also ISO 11737-1 and ISO 14160.
4.2.1.4 Are there unwanted outputs of substances?
The possible presence of toxic residue related to the manufacturing process utilized or degradation
by-products shall be addressed taking into account the physical characteristics (e.g. porosity,
heterogeneity) and chemical composition of animal tissues or derivatives.
NOTE See also ISO 10993-1, ISO 10993-9, ISO 10993-17, ISO 10993-18 and ISO 10993-19.
4.2.2 Identification of hazards and hazardous situations
The possible hazards associated with animal tissues or derivatives shall be identified and documented.
Particular attention shall be applied to possible hazards posed by animal tissues or derivatives with
regard to:
— potential contamination by transmissible agents and their susceptibility to elimination and/or
inactivation during processing;
— potential for contaminants on the finished material which can cause an undesired pyrogenic,
immunological or toxicological reaction;
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— potential for the finished material itself to cause an undesired pyrogenic, immunological or
toxicological reaction.
4.3 Risk evaluation
In accordance with ISO 14971, all identified risks shall be evaluated. Biological safety shall be evaluated
in accordance with ISO 10993-1. Risk evaluation for transmissible agents shall be implemented by
separately addressing the risks related to different categories of transmissible agents. Annex B
identifies the main categories of risk that should be considered. Regarding the TSE risk, compliance
with requirements specified in Annex C for certain animal materials can indicate risk acceptability.
NOTE Annex C combines elements of risk evaluation and risk control.
4.4 Risk control
4.4.1 General
The risk control options shall be documented and justified.
The flowchart in Annex B gives an overview of the risk management process. If additional risks are
identified when using this document, the medical device manufacturer may choose to follow any other
relevant standard or any other route. The decision should be justified and documented.
4.4.2 Risk control for viruses and TSE agents
Risk control shall be implemented by separately addressing the risks related to different categories
of viruses and TSE agents. After defining the characteristics of the product, the medical device
manufacturer shall comply with the relevant requirements of both ISO 22442-2 and ISO 22442-3,
except where either the animal species is such that manufacturers cannot fully meet the requirements
of ISO 22442-2 or an inactivation process in accordance with ISO 22442-3 would cause unacceptable
degradation.
Tallow derivatives, animal charcoal, and amino acids that are acceptable for TSE risk as discussed in
Annex C, due to their processing and not their sourcing, shall also be considered to have acceptable risk
regarding viruses.
Regarding TSE risk, risk control measures specified in Annex C for certain animal materials shall be
applied where relevant. If the manufacturer considers any requirement not to be relevant, the rationale
and justification shall be documented.
For medical devices where an inactivation process causes unacceptable degradation, manufacturers
may rely on ISO 22442-2 in order to meet the requirements of this document.
If the animal species is such that manufacturers cannot fully meet the requirements of ISO 22442-2, they
shall demonstrate that the level of inactivation of transmissible agents in a validated manufacturing
process, as required in ISO 22442-3, is sufficient to achieve an acceptable level of risk.
NOTE Criteria and principles relevant to the management of TSE risks are described in Annex D. Annex D
contains information on relevant risk control measures.
4.4.3 Risk control of other hazards
Risk control related to bacteria, moulds and yeasts, as well as undesired pyrogenic, immunological and
toxicological reactions shall be implemented according to available standards.
Tallow derivatives, animal charcoal, and amino acids that are acceptable for TSE risk as discussed in
Annex C, due to their processing and not their sourcing, shall also be considered to have acceptable risk
regarding bacteria, moulds and yeasts, subject to maintenance of proper storage conditions.
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oSIST prEN ISO 22442-1:2018
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The manufacturer shall conduct periodic microbiological studies to identify and quantify the initial
bioburden of the incoming animal material for the production of the medical device.
NOTE The following International Standards may be relevant:
a) ISO 11135, ISO 11137, ISO 11737-1, ISO 13408, ISO 14160, ISO 14937, ISO 17664 and ISO 17665-1, which can
be relevant for bacteria, moulds and yeasts (see References [19] to[33]);
b) all relevant parts of ISO 10993, which can be used to manage risks related to undesired pyrogenic,
immunological or toxicological reactions (see References [1] to[18]).
The use of these International Standards is illustrated in Annex B.
4.4.4 Residual risk evaluation
4.4.4.1 General
Residual risk evaluation shall be performed for each risk.
4.4.4.2 TSE risk
The TSE risk may be judged acceptable if the following criteria are both met, taking into account the
availability of alternative materials:
a) the residual risk estimate indicates that the TSE risk has been controlled at an acceptable level;
b) the medical benefit arising from the intended use of the device is judged to outweigh the residual
risk estimate.
NOTE Guidance on risk management applicable to TSE agents is given in Annex D. Acceptability can be based
on conformity with requirements specific to some animal materials given in Annex C or requirements relevant to
sourcing, collection and handling of bovine materials given in ISO 22442-2:2015, Annex A.
Regarding the TSE residual risk, specific considerations are provided in Annex C. Some derivatives such
as tallow derivatives, animal charcoal, milk derivatives, wool derivatives and amino acids manufactured
according to conditions mentioned in Annex C are considered as presenting an acceptable TSE risk.
Where the TSE risk has not been controlled at a level that presents an acceptable level of risk to users
or recipients, the overall risk may only be judged acceptable when balanced by exceptional benefit and
feasibility considerations.
4.5 Evaluation of overall residual risk acceptability
4.5.1 General
The evaluation of the overall residual risk acceptability shall take into account the balance between
the residual risk after implementation of all risk control measures and the expected medical benefit, as
c
...
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