SIST EN ISO 22442-2:2021
(Main)Medical devices utilizing animal tissues and their derivatives - Part 2: Controls on sourcing, collection and handling (ISO 22442-2:2020)
Medical devices utilizing animal tissues and their derivatives - Part 2: Controls on sourcing, collection and handling (ISO 22442-2:2020)
This document specifies requirements for controls on the sourcing, collection, and handling (which
includes storage and transport) of animals and tissues for the manufacture of medical devices utilizing
materials of animal origin other than in vitro diagnostic medical devices. It applies where required by
the risk management process as described in ISO 22442-1.
NOTE Selective sourcing is especially important for transmissible spongiform encephalopathy (TSE) risk
management, i.e. when utilising animal tissue and/or their derivative originating from bovine, ovine and caprine
species, deer, elk, mink or cats.
This document does not cover the utilization of human tissues in medical devices.
This document does not specify a quality management system for the control of all stages of production
of medical devices.
Tierische Gewebe und deren Derivate, die zur Herstellung von Medizinprodukten eingesetzt werden - Teil 2: Kontrollen der Beschaffung, Materialgewinnung und Handhabung (ISO 22442-2:2020)
In diesem Dokument werden die Anforderungen an die Kontrolle der Beschaffung, Materialgewinnung und Handhabung (einschließlich Lagerung und Transport) von Tieren und Geweben festgelegt, die zur Herstellung von Medizinprodukten eingesetzt werden, mit Ausnahme von in-vitro-Diagnostika, unter Verwendung von Materialien tierischen Ursprungs. Es kommt dort zum Einsatz, wo der Risikomanagementprozess nach ISO 22442-1 dies vorschreibt.
ANMERKUNG Die selektive Beschaffung ist beim Risikomanagement in Bezug auf übertragbare spongiforme Enzephalopathie (TSE) besonders wichtig, d. h. falls tierische Gewebe und/oder ihre Derivate die von Rindern, Schafen, oder Ziegenspezies, Hirschen, Elchen, Nerz oder Katze verwendet werden.
Dieses Dokument behandelt nicht die Verwendung menschlichen Gewebes in Medizinprodukten.
Dieses Dokument legt kein Qualitätsmanagementsystem zur Kontrolle aller Produktionsschritte eines Medizinproduktes fest.
Dispositifs médicaux utilisant des tissus animaux et leurs dérivés - Partie 2: Contrôles de l'origine, de la collecte et du traitement (ISO 22442-2:2020)
Le présent document spécifie les exigences relatives aux contrôles de l'origine, de la collecte et du traitement (qui comprend le stockage et le transport) d'animaux et de tissus destinés à la fabrication de dispositifs médicaux, autres que les dispositifs médicaux de diagnostic in vitro, utilisant des matériaux d'origine animale. Il s'applique lorsque cela est requis par le processus de gestion des risques tel que décrit dans l'ISO 22442‑1.
NOTE Le choix de l'origine est jugé particulièrement important pour la gestion des risques d'encéphalopathie spongiforme transmissible (EST), c'est-à-dire lors de l'utilisation de tissus animaux et/ou de leurs dérivés provenant d'espèces bovines, ovines, caprines, de cerfs, d'élans, de visons ou de chats.
Le présent document ne couvre pas l'utilisation de tissus humains dans les dispositifs médicaux.
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.
Medicinski pripomočki, ki uporabljajo živalska tkiva in njihove derivate - 2. del: Nadzor pri nabavi, zbiranju in ravnanju z njimi (ISO 22442-2:2020)
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 22442-2:2021
01-februar-2021
Nadomešča:
SIST EN ISO 22442-2:2016
Medicinski pripomočki, ki uporabljajo živalska tkiva in njihove derivate - 2. del:
Nadzor pri nabavi, zbiranju in ravnanju z njimi (ISO 22442-2:2020)
Medical devices utilizing animal tissues and their derivatives - Part 2: Controls on
sourcing, collection and handling (ISO 22442-2:2020)
Tierische Gewebe und deren Derivate, die zur Herstellung von Medizinprodukten
eingesetzt werden - Teil 2: Kontrollen der Beschaffung, Materialgewinnung und
Handhabung (ISO 22442-2:2020)
Dispositifs médicaux utilisant des tissus animaux et leurs dérivés - Partie 2: Contrôles de
l'origine, de la collecte et du traitement (ISO 22442-2:2020)
Ta slovenski standard je istoveten z: EN ISO 22442-2:2020
ICS:
11.040.99 Druga medicinska oprema Other medical equipment
11.120.01 Farmacija na splošno Pharmaceutics in general
SIST EN ISO 22442-2:2021 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 22442-2:2021
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SIST EN ISO 22442-2:2021
EN ISO 22442-2
EUROPEAN STANDARD
NORME EUROPÉENNE
December 2020
EUROPÄISCHE NORM
ICS 11.100.20 Supersedes EN ISO 22442-2:2015
English Version
Medical devices utilizing animal tissues and their
derivatives - Part 2: Controls on sourcing, collection and
handling (ISO 22442-2:2020)
Dispositifs médicaux utilisant des tissus animaux et Tierische Gewebe und deren Derivate, die zur
leurs dérivés - Partie 2: Contrôles de l'origine, de la Herstellung von Medizinprodukten eingesetzt werden -
collecte et du traitement (ISO 22442-2:2020) Teil 2: Kontrollen der Beschaffung, Materialgewinnung
und Handhabung (ISO 22442-2:2020)
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 22442-2:2020 E
worldwide for CEN national Members.
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SIST EN ISO 22442-2:2021
EN ISO 22442-2:2020 (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 22442-2:2021
EN ISO 22442-2:2020 (E)
European foreword
This document (EN ISO 22442-2:2020) 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 22442-2:2015.
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 22442-1 EN ISO 22442-1:2020 ISO 22442-1:2020
3
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SIST EN ISO 22442-2:2021
EN ISO 22442-2:2020 (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 22442-2:2020 has been approved by CEN as EN ISO 22442-2:2020 without any
modification.
4
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SIST EN ISO 22442-2:2021
EN ISO 22442-2:2020 (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 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 International Standard and Directive 93/42/EEC as
amended by Commission Regulation (EU) No 722/2012
Essential Requirements Clause(s)/sub-clause(s)
Remarks/Notes
of Directive 93/42/EEC of this EN
Covered for the sourcing, collection
and handling of materials of animal
origin chosen for the manufacture of
7.1 first indent only 4 ,5, 6, 7, 8 and Annex A
medical devices. Not covered for
flammability. Not covered for
manufacture.
Covered for reducing risks to patients
resulting from contaminants as far as
the sourcing, collection and handling
of materials used in medical devices
7.2 first sentence only 4 ,5, 6, 7, 8 and Annex A based on animal tissues and their
derivatives is concerned, providing
any resulting risks are minimized.
Not covered for packing,
manufacture, transport or storage.
5
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SIST EN ISO 22442-2:2021
EN ISO 22442-2:2020 (E)
Essential Requirements Clause(s)/sub-clause(s)
Remarks/Notes
of Directive 93/42/EEC of this EN
Covered for reducing risks of
infection to patients as far as the
sourcing, collection and handling of
materials used in medical devices
8.1 based on animal tissues and their
4 ,5, 6, 7, 8 and Annex A
derivatives is concerned, providing
first sentence only
any resulting risks are eliminated or
reduced as far as possible. Not
covered for manufacture.
8.2
Covered for the handling of materials
4 ,5, 6, 7, 8 and Annex A used in medical devices based on
first paragraph of third
animal tissues and their derivatives
paragraph only
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 Art.
Regulation (EU) No 722/2012
4 ,5, 6, 7, 8 and Annex A
1.2.
The Regulation is therefore specific to
TSE risks. Annex I of the Regulation
requires implementation of risk
control measures, including controls
on sourcing, collection and handling
of animal-derived material, to
manage TSE risks.
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 22442-2:2021
INTERNATIONAL ISO
STANDARD 22442-2
Third edition
2020-09
Medical devices utilizing animal
tissues and their derivatives —
Part 2:
Controls on sourcing, collection and
handling
Dispositifs médicaux utilisant des tissus animaux et leurs dérivés —
Partie 2: Contrôles de l'origine, de la collecte et du traitement
Reference number
ISO 22442-2:2020(E)
©
ISO 2020
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SIST EN ISO 22442-2:2021
ISO 22442-2:2020(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
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2020 – All rights reserved
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SIST EN ISO 22442-2:2021
ISO 22442-2:2020(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 General requirements . 2
4.1 General . 2
4.2 Quality system elements . 2
4.3 Procedures . 3
4.4 Personnel . 3
4.5 Current regulatory requirements and guidance . 4
5 Sourcing . 4
5.1 General . 4
5.2 Species and strain . 4
5.3 Geography . 4
5.4 Inspection . 4
5.5 Certification . 5
5.6 Traceability . 5
6 Collection . 5
7 Handling . 6
8 Storage, transport and labelling . 6
Annex A (normative) Additional requirements relating to the application of this document
to bovine-sourced materials and other TSE relevant animal species .7
Annex B (informative) Certification and attestation .13
Bibliography .15
© ISO 2020 – All rights reserved iii
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SIST EN ISO 22442-2:2021
ISO 22442-2:2020(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www .iso .org/ patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation of the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to the
World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see www .iso .org/
iso/ foreword .html.
This document was prepared by Technical Committee ISO/TC 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 22442-2:2015).
The main changes compared to the previous version are as follows:
— update of the weblink on stunning technique in A.3.2.5 Note 1;
— clarification on scope inclusion of cervid-sourced materials, and other TSE susceptible species;
— clarification on atypical BSE types, especially in combination with intracranial applications;
— enhanced expectation of using validated biochemical testing to establish TSE presence.
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 22442-2:2021
ISO 22442-2:2020(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).
Tissues and derivatives for use in medical devices are typically obtained by the manufacturer from
a range of sources such as animal herds or flocks and commercial harvesting (including fishing).
Some specialized industries also process materials of animal origin to manufacture a finished
product (e.g. gelatine) which is incorporated as a raw material into the finished medical device by the
manufacturer.
This document is intended to be used in conjunction with the other two parts of the ISO 22442 series.
Local safety regulations can apply. The manufacturers should refer to ISO 22442-3 for information on
the validation of the elimination and/or inactivation of viruses and TSE agents.
It is not a requirement of this document to have a full quality management system during manufacture,
but it does specify requirements for some of the elements of a quality management system. Attention
is drawn to the standards for quality management systems (see ISO 13485) that control all stages of
production or reprocessing of medical devices. The quality management system elements that are
required by this document can form a part of a quality management system conforming to ISO 13485.
© ISO 2020 – All rights reserved v
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SIST EN ISO 22442-2:2021
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SIST EN ISO 22442-2:2021
INTERNATIONAL STANDARD ISO 22442-2:2020(E)
Medical devices utilizing animal tissues and their
derivatives —
Part 2:
Controls on sourcing, collection and handling
1 Scope
This document specifies requirements for controls on the sourcing, collection, and handling (which
includes storage and transport) of animals and tissues for the manufacture of medical devices utilizing
materials of animal origin other than in vitro diagnostic medical devices. It applies where required by
the risk management process as described in ISO 22442-1.
NOTE Selective sourcing is especially important for transmissible spongiform encephalopathy (TSE) risk
management, i.e. when utilising animal tissue and/or their derivative originating from bovine, ovine and caprine
species, deer, elk, mink or cats.
This document does not cover the utilization of human tissues in medical devices.
This document does not specify a quality management system for the control of all stages of production
of medical devices.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements of this document. For dated references, only the edition cited applies. For
undated references, the latest edition of the referenced document (including any amendments) applies.
ISO 22442-1, Medical devices utilizing animal tissues and their derivatives — Part 1: Application of risk
management
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 22442-1 and the following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at http:// www .electropedia .org/
3.1
collection
removal of tissues from animals
3.2
closed herd
herd governed by standard operating procedures (SOPs) that specify criteria restricting admission of
new animals to ensure that all introduced animals are at the same or higher health standard, compared
to the residents of the herd
Note 1 to entry: Such SOPs typically include:
Note 2 to entry: a) a documented veterinary monitoring process;
© ISO 2020 – All rights reserved 1
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SIST EN ISO 22442-2:2021
ISO 22442-2:2020(E)
Note 3 to entry: b) a fully documented disease history, including a fully documented negligible TSE risk status of
the herd including logged TSE history;
Note 4 to entry: c) a process to prevent feeding of mammalian-derived protein, including a fully documented feed
history, source and traceability;
Note 5 to entry: d) a fully documented breeding history;
Note 6 to entry: e) a fully documented use of veterinary medicines and vaccines;
Note 7 to entry: f) a process of traceability towards each individual animal;
Note 8 to entry: g) a process to control introduction of genetic material from animals outside the closed herd,
including from herds with the deviating TSE status;
Note 9 to entry: h) a fully documented record of animals kept with or in close proximity to the closed herd and
procedures to control vermin or pest.
3.3
veterinarian
person designated by the relevant competent authority as suitably qualified for the responsibility
delegated to him or her relating to ante- and post-mortem inspection of animals and/or relevant
certification
Note 1 to entry: Under certain jurisdictions, it is a requirement that the veterinarian be a professionally qualified
person in veterinary medicine.
Note 2 to entry: Under certain jurisdictions, the function of inspection and of certification can be carried
out by different individuals. In such cases, the certificate can be signed by a person who is not designated by
the competent authority. This function is covered in the quality management system of the medical device
manufacturer.
4 General requirements
4.1 General
Apply the requirements of this document as determined by the benefit-risk-assessment
(see ISO 22442-1).
Annex A shall be applied as appropriate.
4.2 Quality system elements
A documented system shall be established and maintained to control the quality of materials of animal
origin and shall be verified by the medical device manufacturer. Specific requirements relating to
collection are included in Clause 6.
Compliance is checked by inspection of the appropriate documents, including:
a) specification of the age and of the geographical origin (such as country or region) of the animal
material, state of health of the animals, and acceptance criteria for animals taking into account
the source-species, perceived risk from pathogens, and ability to obtain appropriate assurances,
including full traceability to the slaughterhouse.
The geographical origin can include the animal’s place of birth and the countries or regions in which
it has lived during its lifetime as well as its place of slaughter. It is advisable that the manufacturer
document the extent to which the geographical origin of the animal can be traced taking into
account the application of risk management (see ISO 22442-1);
b) hygiene and quality assurance requirements to be met by the slaughterer including the provisions
in the slaughterhouse to prevent cross-contamination within and between animals;
2 © ISO 2020 – All rights reserved
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SIST EN ISO 22442-2:2021
ISO 22442-2:2020(E)
c) procedures for the collection, preservation, handling, storage, and transport of materials of
animal origin;
d) documented evidence of the effectiveness of controls defined in a), b), and c);
e) records to be maintained [including as a minimum items a), b), c), and d). See also 5.5.
For the control of processed animal material suppliers, the medical device manufacturer shall document,
to the extent feasible, the practices of the specialized industries to which clauses of the various parts of
ISO 22442 have been applied.
Manufacturers should apply relevant provisions of ISO 22442 to natural substances such as milk, hair,
and wool, although these are not covered by the definition of derivatives.
[3],[5]
NOTE The use of risk analysis/risk management tools (such as HACCP, FMEA ) are useful in determining
residual risk.
4.3 Procedures
The documented procedures and instructions required by this document shall be established,
...
SLOVENSKI STANDARD
oSIST prEN ISO 22442-2:2019
01-januar-2019
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Medical devices utilizing animal tissues and their derivatives - Part 2: Controls on
sourcing, collection and handling (ISO/DIS 22442-2:2018)
Tierische Gewebe und deren Derivate, die zur Herstellung von Medizinprodukten
eingesetzt werden - Teil 2: Kontrollen der Beschaffung, Materialgewinnung und
Handhabung (ISO/DIS 22442-2:2018)
Dispositifs médicaux utilisant des tissus animaux et leurs dérivés - Partie 2: Contrôles de
l'origine, de la collecte et du traitement (ISO/DIS 22442-2:2018)
Ta slovenski standard je istoveten z: prEN ISO 22442-2
ICS:
11.120.01 Farmacija na splošno Pharmaceutics in general
oSIST prEN ISO 22442-2:2019 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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oSIST prEN ISO 22442-2:2019
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oSIST prEN ISO 22442-2:2019
DRAFT INTERNATIONAL STANDARD
ISO/DIS 22442-2
ISO/TC 194/SC 1 Secretariat: DIN
Voting begins on: Voting terminates on:
2018-11-22 2019-02-14
Medical devices utilizing animal tissues and their
derivatives —
Part 2:
Controls on sourcing, collection and handling
Dispositifs médicaux utilisant des tissus animaux et leurs dérivés —
Partie 2: Contrôles de l'origine, de la collecte et du traitement
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
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NATIONAL REGULATIONS.
ISO/DIS 22442-2:2018(E)
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Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 General requirements . 2
4.1 General . 2
4.2 Quality system elements . 2
4.3 Procedures . 3
4.4 Personnel . 3
4.5 Current regulatory requirements and guidance . 4
5 Sourcing . 4
5.1 General . 4
5.2 Species and strain . 4
5.3 Geography . 4
5.4 Inspection . 4
5.5 Certification . 5
5.6 Traceability . 5
6 Collection . 5
7 Handling . 6
8 Storage and transport . 6
Annex A (normative) Additional requirements relating to the application of this document
to bovine-sourced materials . 7
Annex B (informative) Certification and attestation .12
Annex C (informative) Veterinary services .14
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 .15
Bibliography .17
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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.o rg/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, Subcommittee SC 1, Tissue product safety.
This third edition cancels and replaces the second edition (ISO 22442-2:2015), of which it constitutes a
minor revision.
The major changes are:
— Update of weblink on stunning technique in Annex A, A.3.2.5 Note 1;
— Clarification on scope inclusion of cervid-sourced materials, and other TSE susceptible species;
— Clarification on atypical BSE types, especially in combination with intracranial applications;
— Enhanced expectation of using validated biochemical testing to establish TSE presence;
— Update of weblink in Annex C;
— Update of bibliography;
— Editorial revision.
A list of all parts in the ISO 22442- series can be found on the ISO website.
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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).
Tissues and derivatives for use in medical devices are typically obtained by the manufacturer from a
range of sources such as animal herds or flocks and commercial harvesting (including fishing). Some
specialized industries also process materials of animal origin to manufacture a finished product (e.g.
gelatine) which is incorporated as a raw material into the finished medical device by the manufacturer.
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.
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DRAFT INTERNATIONAL STANDARD ISO/DIS 22442-2:2018(E)
Medical devices utilizing animal tissues and their
derivatives —
Part 2:
Controls on sourcing, collection and handling
1 Scope
This document specifies requirements for controls on the sourcing, collection, and handling (which
includes storage and transport) of animals and tissues for the manufacture of medical devices utilizing
materials of animal origin other than in vitro diagnostic medical devices. It applies where required by
the risk management process as described in ISO/DIS 22442-1.
NOTE 1 Selective sourcing is considered to be especially important for transmissible spongiform
encephalopathy (TSE) risk management, i.e. when utilising animal tissue and/or their derivative originating
from bovine, ovine and caprine species, deer, elk, mink or cats.
In addition, local safety regulation may be applied to ensure a clean basic handling of animals towards
viral and bacterial loads (see also 5.5). The manufacturers should refer to ISO 22442-3 for information
on the validation of the elimination and/or inactivation of viruses and TSE agents.
This document does not cover the utilization of human tissues in medical devices.
This document does not specify a quality management system for the control of all stages of production
of medical devices.
It is not a requirement of this document to have a full quality management system during manufacture,
but it does specify requirements for some of the elements of a quality management system. Attention
is drawn to the standards for quality management systems (see ISO 13485) that control all stages of
production or reprocessing of medical devices. The quality management system elements that are
required by this document can form a part of a quality management system conforming to ISO 13485.
NOTE 2 A general principle for the application of this International Standard is that it is advisable to give due
consideration to the requirements and recommendations contained in all three parts of the standard.
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/DIS 22442-1:2018, Medical devices utilizing animal tissues and their derivatives — Part 1: Application
of risk management
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO/DIS 22442-1 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
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3.1
collection
removal of tissues from animals
3.2
closed herd or colony
herd or colony governed by standard operating procedures (SOPs) that specify criteria restricting
admission of new animals to assure that all introduced animals are at the same or higher health
standard, compared to the residents of the herd or colony. Such SOPs should include:
a) a documented veterinary monitoring process;
b) logging of TSE history;
c) a process to prevent feeding of mammalian-derived protein;
d) a fully documented breeding history;
e) a fully documented use of veterinary medicines and vaccines;
f) a process of traceability towards each individual animal;
g) a process to control introduction of genetic material from herds with the deviating TSE status
3.3
veterinarian
person designated by the relevant competent authority as suitably qualified for the responsibility
delegated to him or her relating to ante- and post-mortem inspection of animals and/or relevant
certification
Note 1 to entry: Under certain jurisdictions, it is a requirement that the veterinarian be a professionally qualified
person in veterinary medicine.
Note 2 to entry: Under certain jurisdictions, the function of inspection and of certification can be carried
out by different individuals. In such cases, the certificate can be signed by a person who is not designated by
the competent authority. This function is covered in the quality management system of the medical device
manufacturer.
4 General requirements
4.1 General
Apply the requirements of this document as determined by the risk assessment (see ISO/DIS 22442-1).
Annex A shall be applied as appropriate.
4.2 Quality system elements
A documented system shall be established and maintained to control the quality of materials of animal
origin and shall be verified by the medical device manufacturer. Specific requirements relating to
collection are included in Clause 6.
This system shall address the animal source and the following factors:
a) specification of the geographical origin (such as country or region) of the animal material, state of
health of the animals, and acceptance criteria for animals taking into account the source-species,
perceived risk from pathogens, and ability to obtain appropriate assurances;
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NOTE 1 The geographical origin can include the animal’s place of birth and the countries or regions in
which it has lived during its lifetime as well as its place of slaughter. It is advisable that the manufacturer
document the extent to which the geographical origin of the animal can be traced taking into account the
application of risk management (see ISO/DIS 22442-1).
b) hygiene and quality assurance requirements to be met by the slaughterer including the provisions
in the slaughterhouse to prevent cross-contamination within and between animals;
c) procedures for the collection, preservation, handling, storage, and transport of materials of
animal origin;
d) documented evidence of the effectiveness of controls defined in a), b), and c);
e) records to be maintained [including as a minimum items a), b), c), and d). See also 5.5].
For the control of processed animal material suppliers, the medical device manufacturer shall document,
to the extent feasible, the practices of the specialized industries to which clauses of the various parts of
ISO 22442 have been applied.
Manufacturers should apply relevant provisions of ISO 22442 to natural substances such as milk, hair,
and wool, although these are not covered by the definition of derivatives.
NOTE 2 The use of risk analysis/risk management tools [such as HACCP, FMEA (see ISO 14971:2007, Annex G)]
are useful in determining residual risk.
4.3 Procedures
The documented procedures and instructions required by this part of ISO 22442 shall be established,
implemented, and maintained. These procedures and instructions shall be approved on issue and shall
be controlled as follows.
The manufacturer shall establish and maintain procedures to control all documents and data that relate
to the requirements of this document. These documents shall be reviewed and approved for adequacy
by authorized personnel prior to issue.
This control shall ensure that:
a) the pertinent issues of appropriate documents are available at all locations where operations
essential to the effective functioning of the quality system are performed, and
b) obsolete documents are promptly removed from all points of issue or use.
Changes to documents shall be reviewed and approved by the same functions/organizations that
performed the original review and approval unless specifically designated otherwise. The designated
organizations shall have access to pertinent background information upon which to base their review
and approval.
Where practicable, the nature of each change shall be identified in the document or the appropriate
attachments.
A master list or equivalent document control procedure shall be established to identify the current
revision of documents in order to preclude the use of non-applicable documents.
4.4 Personnel
Responsibility for the collection, handling, and storage of materials shall be assigned to qualified
personnel as follows.
The manufacturer shall establish and maintain procedures for identifying the training needs and
provide for the training of all personnel performing activities affecting quality.
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The manufacturer shall ensure that personnel performing specific assigned tasks are qualified on the
basis of appropriate education, training, and/or experience as required. Appropriate records of training
shall be maintained.
Personnel directly involved in the collection and handling of material of animal origin shall be personnel
employed by the device manufacturer or designated and adequately trained abattoir employees or the
equivalent. The same requirements apply to personnel of all subcontractors.
The manufacturer shall identify the in-house verification requirements and shall provide adequate
resources and assign trained personnel for verification activities.
Audits shall be carried out by personnel independent of those having direct responsibility for the work
being performed.
4.5 Current regulatory requirements and guidance
Due account shall be taken of relevant current regional regulatory requirements or guidance including
[5]
the OIE International Animal Health Code.
5 Sourcing
5.1 General
5.2 to 5.6 and Clauses 6 to 8 shall be applied by the suppliers of animal materials, intermediaries, and
medical device manufacturers as relevant under the risk management plan in compliance with ISO/
DIS 22442-1.
The animal material shall not be compromised by cross-contamination before, during, or after slaughter.
Animals shall be confirmed as having been declared fit for human consumption (see 5.5).
It is the responsibility of the manufacturer to ensure that the material is fit for its intended use.
5.2 Species and strain
For each material or derivative, the risk of certain diseases is dependent on the animal species and
possibly strain, and this shall be taken into account for the establishment of control measures.
5.3 Geography
The risk of certain diseases is dependent on the geographical origin and this shall be taken into account
for the establishment of control measures.
Geographical origin can include conception, birth, rearing, and slaughtering (for bovine species, see
Annex A).
If required by the risk management process, in the case of domesticated/farmed species, the
geographical region/country of birth and the summary of main locations of residence up to time of
slaughter shall be recorded.
In the case of wild species, the region/location of capture and the country/region of birth shall be
recorded if known. The use of wild mammalian species shall be addressed in the risk assessment (see
ISO/DIS 22442-1).
5.4 Inspection
Sourcing of animal material shall be subject to control and individual inspection by a veterinarian.
There will, however, be some source-species where this is not possible (e.g. fish, crustaceans). If
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individual animals cannot be inspected, the justification for this shall be documented and a relevant
sampling plan provided.
Bovine, caprine, cervid, equine, ovine, and porcine species shall be subject to ante-mortem veterinary
inspection. Animals showing locomotive system abnormalities or neurological disorders shall not be
used for the production of medical devices except for tallow derivatives, animal charcoal, and amino
acids that are acceptable as discussed in ISO/DIS 22442-1:2018, 4.4.2 and 4.4.3, due to their processing
and not their sourcing.
Prior to certification, a post-mortem inspection of bovine, caprine, cervid, equine, ovine, and porcine
species shall be performed by a veterinarian immediately after slaughter according to local custom and
practice. The inspection shall include at least the following:
a) visual inspection;
b) palpation of specified organs;
c) incision of organs and lymph nodes;
d) investigation of anomalies, e.g. inconsistency, colour, and smell;
e) if necessary, laboratory tests.
Where indicated by risk assessment, for materials (including pooled blood supplies) for direct use
in medical devices and that are not subject to a validated process to reduce TSE risk in line with
ISO 22442-3, consideration shall be given to the application of a validated biochemical test for the
presence of TSE in the source animal.
Animal tissues derived from certain species (e.g. fish, crustaceans) require a modified approach since
veterinary surveillance is not practicable in the same way as for other animal tissues. Manufacturers
should apply relevant sections of this document to such materials, but may need to rely on other
procedures which have been shown to be effective for risk reduction (see ISO/DIS 22442-1).
5.5 Certification
Material of animal origin intended for utilization in medical devices shall originate from animals
confirmed by a veterinarian as being fit for human consumption. Records to demonstrate conformance
with veterinary inspection criteria at the abattoir, certificate details, and source shall be available (see
for example, Annex B). For species where such certification by a veterinarian cannot be obtained, a status
equivalent to “fit for human consumption” is required such as a confirmation of apparent good health.
5.6 Traceability
Where the risk management undertaken according to ISO/DIS 22442-1 indicates that it is both necessary
and feasible, a traceability system shall be established. The extent of traceability shall be defined by the
outcome of the risk assessment taking into account those official information systems that exist.
NOTE Traceability may not be practicable if materials of animal origin are collected, pooled, and
manufactured by processed animal material suppliers.
6 Collection
6.1 Between the manufacturer of the medical device and the supplier of material of animal origin,
there shall be a technical agreement defining the following:
— the limits of responsibilities;
— specifications of the material;
— documentation;
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— inspection criteria;
— procedures (including specific measures to prevent cross-contamination);
— audits;
— procedures for ensuring that all deliveries have traceability of relevant certificates.
Materials derived from TSE susceptible species (including pooled blood supplies) intended for direct
use in medical devices and that are not subject to a validated process in line with ISO 22442-3 to reduce
TSE risks to an acceptable level determined by the risk management process shall be harvested from
slaughterhouses designated by the medical device manufacturer.
6.2 The manufacturer shall be responsible for ensuring that the collection of the material is conducted
in accordance with the documented procedures.
6.3 The manufacturer shall review and specify the systems for certification and traceability when
tissues of animal origin are pooled at the place of slaughter or subsequently. The limits of pooling
permitted shall be justified and documented.
7 Handling
7.1 If any material of animal origin requires further dissection or trimming, it shall be removed as
soon as possible to an area separate from that used for slaughtering and collection. This area shall be
suitably equipped and maintained at an appropriate level of cleanliness and environmental protection.
Implements for dissection and trimming shall be kept clean to minimize risk of cross-contamination.
Ideally, a dedicated set of tools should be used for trimming and kept separate from the ones used for
harvesting.
7.2 Source materials to be utilized in medical devices shall be segregated for delivery according to a
documented procedure.
7.3 The manufacturer shall b
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