ISO 22442-2:2020
(Main)Medical devices utilizing animal tissues and their derivatives — Part 2: Controls on sourcing, collection and handling
Medical devices utilizing animal tissues and their derivatives — Part 2: Controls on sourcing, collection and handling
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.
Dispositifs médicaux utilisant des tissus animaux et leurs dérivés — Partie 2: Contrôles de l'origine, de la collecte et du traitement
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.
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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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ISO 22442-2:2020(E)
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© ISO 2020
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
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Published in Switzerland
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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
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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.
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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.
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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;
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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;
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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,
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.
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.
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ISO 22442-2:2020(E)
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
[4], [13]
the OIE International Animal Health Code .
5 Sourcing
5.1 General
Subclauses 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 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).
For the animal material sourced from species that are not intended for human consumption the
justification for the missing inspection and certification is to be documented. Relevant quality criteria
for this type of material are to be defined by the manufacturer.
It is the responsibility of the manufacturer to ensure that the material is fit for its intended use.
In case animal by-products not intended for human consumption are sourced, these have to be ‘Category
[16]
3 (i.e. safe) materials or equivalent’ .
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.
NOTE Specific guidance as regards requirements for bovine blood can be found in the “Guideline on the use
[14]
of bovine serum in the manufacture of human biological medicinal products” .
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 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, cervids,
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ISO 22442-2:2020(E)
mink, cat). If individual animals cannot be inspected, the justification for this shall be documented and
a relevant sampling plan provided.
Bovine, caprine, 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; Tallow derivatives, animal charcoal, and amino acids
[13], [16]
`Category 3 (i.e. safe) materials or equivalent’ .
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. Such validated in vitro tests are indicative for TSE positive status
but can only be relied on for confirming the negative stats of an animal once such test is universally
accepted as being state of the art on this aspect.
Animal tissues derived from certain species (e.g. fish, crustaceans, cervids, mink, cat) 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 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 22442-1 indicates that it is both necessary
and feasible, a traceability system shall be established. Traceability to the slaughterhouse should
be assured, as well as traceability by suppliers of processed animal materials. The exact extent of
traceability shall be defined by the outcome of the risk-benefit assessment taking into account those
official information systems that exist.
NOTE Traceability cannot 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;
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ISO 22442-2:2020(E)
— specifications of the material;
— documentation provided by the supplier allowing the manufacturer to meet the requirements of
this document;
— 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 be responsible for ensuring that the handling of the material is conducted
in accordance with the documented procedures.
8 Storage, transport and labelling
8.1 Collected material shall be stored and transported in closed or other appropriate containers.
8.2 The conditions for storage and transport shall not compromise compliance with the relevant
qualities of the animal material, in particular, by environmental or enzymatic degradation or microbial
proliferation.
8.3 The manufacturer shall be responsible for ensuring that the storage, transport and labelling of the
material is conducted in accordance with the documented procedures.
8.4 Primary container of the collected material shall be labelled appropriately to avoid cross
contamination and mix up during the transport and storage. The label shall at least contain details of the
material, collection date and the location for traceability.
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ISO 22442-2:2020(E)
Annex A
(normative)
Additional requirements relating to the application of this
document to bovine-sourced materials and other TSE relevant
animal species
A.1 General
This annex contains requirements applicable to non-viable material derived from cattle and intended for
use in medical devices. ISO 22442-1 requires that for materials sourced from species that are susceptible
to transmissible spongiform encephalopathies (TSEs), risk control measures are implemented and the
overall TSE risk is estimated and assessed in relation to the medical b
...
NORME ISO
INTERNATIONALE 22442-2
Troisième édition
2020-09
Dispositifs médicaux utilisant des
tissus animaux et leurs dérivés —
Partie 2:
Contrôles de l'origine, de la collecte et
du traitement
Medical devices utilizing animal tissues and their derivatives —
Part 2: Controls on sourcing, collection and handling
Numéro de référence
ISO 22442-2:2020(F)
©
ISO 2020
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ISO 22442-2:2020(F)
DOCUMENT PROTÉGÉ PAR COPYRIGHT
© ISO 2020
Tous droits réservés. Sauf prescription différente ou nécessité dans le contexte de sa mise en œuvre, aucune partie de cette
publication ne peut être reproduite ni utilisée sous quelque forme que ce soit et par aucun procédé, électronique ou mécanique,
y compris la photocopie, ou la diffusion sur l’internet ou sur un intranet, sans autorisation écrite préalable. Une autorisation peut
être demandée à l’ISO à l’adresse ci-après ou au comité membre de l’ISO dans le pays du demandeur.
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Publié en Suisse
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ISO 22442-2:2020(F)
Sommaire Page
Avant-propos .iv
Introduction .v
1 Domaine d’application . 1
2 Références normatives . 1
3 Termes et définitions . 1
4 Exigences générales . 2
4.1 Généralités . 2
4.2 Éléments du système qualité . 2
4.3 Modes opératoires . 3
4.4 Personnel . 4
4.5 Exigences réglementaires et recommandations en vigueur . 4
5 Origine . 4
5.1 Généralités . 4
5.2 Espèce et souche . . 4
5.3 Origine géographique . 5
5.4 Inspection . 5
5.5 Certification . 6
5.6 Traçabilité . 6
6 Collecte . 6
7 Traitement . 7
8 Stockage, transport et étiquetage . 7
Annexe A (normative) Exigences supplémentaires relatives à l’application du présent
document aux matériaux d’origine bovine et à d’autres espèces animales
concernées par l’EST . 8
Annexe B (informative) Certification et attestation .15
Bibliographie .17
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ISO 22442-2:2020(F)
Avant-propos
L’ISO (Organisation internationale de normalisation) est une fédération mondiale d’organismes
nationaux de normalisation (comités membres de l’ISO). L’élaboration des Normes internationales est
en général confiée aux comités techniques de l’ISO. Chaque comité membre intéressé par une étude
a le droit de faire partie du comité technique créé à cet effet. Les organisations internationales,
gouvernementales et non gouvernementales, en liaison avec l’ISO participent également aux travaux.
L’ISO collabore étroitement avec la Commission électrotechnique internationale (IEC) en ce qui
concerne la normalisation électrotechnique.
Les procédures utilisées pour élaborer le présent document et celles destinées à sa mise à jour sont
décrites dans les Directives ISO/IEC, Partie 1. Il convient, en particulier de prendre note des différents
critères d’approbation requis pour les différents types de documents ISO. Le présent document a été
rédigé conformément aux règles de rédaction données dans les Directives ISO/IEC, Partie 2 (voir www
.iso .org/ directives).
L’attention est appelée sur le fait que certains des éléments du présent document peuvent faire l’objet de
droits de propriété intellectuelle ou de droits analogues. L’ISO ne saurait être tenue pour responsable
de ne pas avoir identifié de tels droits de propriété et averti de leur existence. Les détails concernant
les références aux droits de propriété intellectuelle ou autres droits analogues identifiés lors de
l’élaboration du document sont indiqués dans l’Introduction et/ou dans la liste des déclarations de
brevets rédigées par l’ISO (voir www .iso .org/ brevets).
Les appellations commerciales éventuellement mentionnées dans le présent document sont données
pour information, par souci de commodité, à l’intention des utilisateurs et ne sauraient constituer un
engagement.
Pour une explication de la nature volontaire des normes, de la signification des termes et expressions
spécifiques de l’ISO liés à l’évaluation de la conformité, ou pour toute autre information au sujet de
l’adhésion de l’ISO aux principes de l’Organisation mondiale du commerce (OMC) concernant les
obstacles techniques au commerce (OTC), voir le lien suivant: www .iso .org/ iso/ fr/ avant -propos .html.
Le présent document a été élaboré par le comité technique ISO/TC 194, Évaluation biologique et clinique
des dispositifs médicaux, sous-comité SC 1, Sécurité des produits tissulaires, en collaboration avec le
comité technique CEN/TC 206, Évaluation biologique et clinique des dispositifs médicaux, du Comité
européen de normalisation (CEN), conformément à l’Accord de coopération technique entre l’ISO et le
CEN (Accord de Vienne).
Cette troisième édition annule et remplace la deuxième édition (ISO 22442-2:2015).
Les principales modifications par rapport à la version précédente sont les suivantes:
— mise à jour du lien URL relatif à la technique d’étourdissement en A.3.2.5, Note 1;
— clarification de l’inclusion dans le domaine d’application des matériaux provenant de cervidés, et
d’autres espèces sensibles aux EST;
— clarification des types d’ESB particuliers, notamment en combinaison avec des applications
intracrâniennes;
— perspective renforcée d’utilisation d’essais biochimiques validés pour établir la présence d’EST.
Une liste de toutes les parties de la série ISO 22442 se trouve sur le site web de l’ISO.
Il convient que l’utilisateur adresse tout retour d’information ou toute question concernant le présent
document à l’organisme national de normalisation de son pays. Une liste exhaustive desdits organismes
se trouve à l’adresse www .iso .org/ members .html.
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ISO 22442-2:2020(F)
Introduction
Certains dispositifs médicaux utilisent des matériaux d’origine animale.
Des tissus d’origine animale et leurs dérivés sont utilisés dans la conception et la fabrication de
dispositifs médicaux pour obtenir des caractéristiques de performance présentant des avantages
par rapport à celles offertes par des matériaux d’origine non animale. La diversité et la quantité de
matériaux d’origine animale utilisés dans les dispositifs médicaux sont variables. Ces matériaux peuvent
constituer une partie importante du dispositif (par exemple, les valves cardiaques d’origine bovine/
porcine, les substituts osseux destinés à être utilisés dans des applications dentaires ou orthopédiques,
les dispositifs hémostatiques), peuvent être un revêtement ou une enduction du produit (par exemple, le
collagène, la gélatine, l’héparine) ou peuvent être utilisés dans le processus de fabrication du dispositif
(par exemple, les dérivés du suif tels que les oléates et les stéarates, le sérum de veau fœtal, les enzymes,
les milieux de culture).
Les tissus et les dérivés utilisés dans les dispositifs médicaux sont généralement obtenus par le
fabricant à partir de plusieurs sources telles que les troupeaux ou les élevages d’animaux et les
cultures commerciales (y compris la pêche). Certaines industries spécialisées fabriquent également des
matériaux d’origine animale destinés à la fabrication d’un produit fini (par exemple, la gélatine) que le
fabricant incorpore en tant que matière première dans le dispositif médical final.
Le présent document est destiné à être utilisé conjointement avec les deux autres parties de la série
ISO 22442. Des réglementations locales de sécurité peuvent s’appliquer. Il convient que les fabricants
se réfèrent à l’ISO 22442-3 pour les informations relatives à la validation de l’élimination et/ou de
l’inactivation des virus et des agents EST.
Le présent document n’exige pas un système de management de la qualité complet lors de la fabrication,
mais il spécifie des exigences pour la plupart des éléments d’un système de management de la qualité.
L’attention est attirée sur les normes 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.
Les éléments du système de management de la qualité qui sont exigés par le présent document peuvent
former une partie d’un système de management de la qualité en conformité avec l’ISO 13485.
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NORME INTERNATIONALE ISO 22442-2:2020(F)
Dispositifs médicaux utilisant des tissus animaux et leurs
dérivés —
Partie 2:
Contrôles de l'origine, de la collecte et du traitement
1 Domaine d’application
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.
2 Références normatives
Les documents suivants sont cités dans le texte de sorte qu’ils constituent, pour tout ou partie de leur
contenu, des exigences du présent document. Pour les références datées, seule l’édition citée s’applique.
Pour les références non datées, la dernière édition du document de référence s’applique (y compris les
éventuels amendements).
ISO 22442-1, Dispositifs médicaux utilisant des tissus animaux et leurs dérivés — Partie 1: Application de la
gestion des risques
3 Termes et définitions
Pour les besoins du présent document, les termes et définitions donnés dans l’ISO 22442-1 ainsi que les
suivants s’appliquent.
L’ISO et l’IEC tiennent à jour des bases de données terminologiques destinées à être utilisées en
normalisation, consultables aux adresses suivantes:
— ISO Online browsing platform: disponible à l’adresse https:// www .iso .org/ obp
— IEC Electropedia: disponible à l’adresse http:// www .electropedia .org/
3.1
collecte
prélèvement de tissus sur un animal
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ISO 22442-2:2020(F)
3.2
élevage clos
élevage régi par des modes opératoires normalisés (MON) qui spécifient des critères restreignant
l’admission de nouveaux animaux pour s’assurer que tous les animaux introduits présentent un état de
santé égal ou supérieur à celui des résidents de l’élevage
Note 1 à l'article: Ces MON comprennent généralement:
a) un processus de contrôles vétérinaires documentés;
b) des antécédents médicaux intégralement documentés, notamment un statut de risque d’EST négligeable
intégralement documenté de l’élevage, y compris des antécédents d’EST enregistrés;
c) un processus pour empêcher l’alimentation utilisant des protéines issues de mammifères, notamment un
historique d’alimentation intégralement documenté, l’origine et la traçabilité;
d) un historique d’élevage intégralement documenté;
e) une utilisation de médicaments et de vaccins vétérinaires intégralement documentée;
f) un processus de traçabilité de chaque animal;
g) un processus de contrôle de l’introduction du matériel génétique provenant d’animaux extérieurs à l’élevage
clos, notamment des élevages présentant le statut EST divergent;
h) un dossier intégralement documenté des animaux gardés avec ou à proximité de l’élevage clos et des modes
opératoires de lutte contre les ravageurs et les nuisibles.
3.3
vétérinaire
personne désignée par l’autorité compétente, possédant la qualification adéquate pour assumer la
responsabilité qui lui a été déléguée quant au contrôle ante mortem et post-mortem des animaux et/ou
à la certification applicable
Note 1 à l'article: Dans certaines juridictions, il est exigé que le vétérinaire soit une personne possédant une
qualification professionnelle en médecine vétérinaire.
Note 2 à l'article: Dans certaines juridictions, la fonction de contrôle et de certification peut être assumée par
différentes personnes. Dans ce cas, le certificat peut être signé par une personne qui n’est pas désignée par
l’autorité compétente. Cette fonction est abordée dans le système de management de la qualité du fabricant de
dispositifs médicaux.
4 Exigences générales
4.1 Généralités
Appliquer les exigences du présent document comme déterminé par l’évaluation du rapport bénéfices-
risques (voir l’ISO 22442-1).
L’Annexe A doit être appliquée le cas échéant.
4.2 Éléments du système qualité
Un système documenté doit être établi, tenu à jour afin de contrôler la qualité des matériaux d’origine
animale et doit être vérifié par le fabricant de dispositifs médicaux. Des exigences particulières relatives
à la collecte sont incluses dans l’Article 6.
La conformité est vérifiée par contrôle des documents appropriés, notamment:
a) la spécification de l’âge et de l’origine géographique (telle que le pays ou la région) du matériau
d’origine animale, l’état de santé et les critères d’acceptation des animaux, compte tenu de leur
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ISO 22442-2:2020(F)
espèce, du risque potentiel lié aux agents pathogènes et de la capacité d’obtenir des assurances
appropriées, notamment la traçabilité intégrale jusqu’à l’abattoir.
L’origine géographique peut comprendre le lieu de naissance de l’animal et les pays ou les régions
où il a vécu, ainsi que le lieu d’abattage. II est préférable que le fabricant documente l’étendue de
la traçabilité géographique de l’animal, compte tenu de l’application de la gestion des risques (voir
l’ISO 22442-1);
b) les exigences en matière d’hygiène et d’assurance qualité auxquelles l’abattoir doit satisfaire, y
compris les dispositions prises dans l’abattoir pour prévenir une contamination croisée intra- et
interanimaux;
c) les modes opératoires de collecte, de conservation, de manipulation, de stockage et de transport
des matériaux d’origine animale;
d) les preuves documentées de l’efficacité des contrôles définis en a), en b) et en c);
e) les enregistrements à conserver [y compris au minimum les points a), b), c) et d)]. Voir
également en 5.5.
Pour contrôler les fournisseurs de matériaux d’origine animale traités, le fabricant de dispositifs
médicaux doit, dans la mesure du possible, documenter les pratiques des industries spécialisées
auxquelles les articles des diverses parties de l’ISO 22442 ont été appliqués.
Il convient que les fabricants appliquent les dispositions correspondantes de l’ISO 22442 aux substances
naturelles telles que le lait, les poils et la laine, bien qu’elles ne soient pas incluses dans la définition des
dérivés.
[3],[5]
NOTE L’utilisation d’outils d’analyse des risques/de gestion des risques (tels que HACCP, FMEA ) est
intéressante lors de la détermination du risque résiduel.
4.3 Modes opératoires
Les modes opératoires et les instructions documentés requis par le présent document doivent être
établis, appliqués et tenus à jour. Ces modes opératoires et ces instructions doivent être approuvés dès
leur diffusion et être contrôlés comme suit.
Le fabricant doit établir et tenir à jour les modes opératoires destinés à vérifier l’ensemble des
documents et des données se rapportant aux exigences du présent document. Des personnes habilitées
à le faire doivent réviser ces documents et approuver leur adéquation avant leur diffusion.
Ce contrôle doit garantir que:
a) les éditions pertinentes des documents appropriés sont disponibles à tous les endroits où des
opérations essentielles au bon fonctionnement du système qualité sont effectuées; et
b) les documents obsolètes sont aussitôt retirés de tous les points de diffusion ou d’utilisation.
Sauf spécification contraire, les modifications apportées aux documents doivent être revues et
approuvées par les mêmes responsables/organismes qui les ont revus et approuvés à l’origine. Les
responsables/organismes désignés doivent avoir accès à toutes informations archivées appropriées sur
lesquelles ils peuvent fonder leur contrôle et leur approbation.
Lorsque cela est réalisable, la nature de chaque modification doit être identifiée dans le document ou
dans les annexes appropriées.
Une liste principale ou un mode opératoire équivalent de contrôle des documents doit être établi(e) pour
identifier la révision de documents en cours, afin d’exclure l’utilisation de documents non applicables.
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ISO 22442-2:2020(F)
4.4 Personnel
La responsabilité de la collecte, du traitement et du stockage des matériaux doit être confiée à un
personnel qualifié, de la manière suivante:
Le fabricant doit établir et tenir à jour des modes opératoires destinés à l’identification des besoins en
formation et prévoir la formation de tout le personnel ayant des activités en rapport avec la qualité.
Le fabricant doit s’assurer que le personnel accomplissant les tâches spécifiques qui lui ont été confiées
est qualifié sur la base du niveau d’études approprié, d’une formation et/ou d’une expérience requise,
selon le cas. Des enregistrements appropriés de la formation doivent être tenus à jour.
Le personnel intervenant directement dans la collecte et le traitement d’un matériau d’origine animale
doit être du personnel employé par le fabricant de dispositifs ou des employés de l’abattoir, désignés et
correctement formés, ou l’équivalent. Les mêmes exigences s’appliquent au personnel de tous les sous-
traitants.
Le fabricant doit identifier les exigences internes en matière de contrôle, fournir les ressources
nécessaires et affecter un personnel formé aux activités de contrôle.
Des audits doivent être effectués par un personnel indépendant de celui qui a la responsabilité directe
du travail effectué.
4.5 Exigences réglementaires et recommandations en vigueur
Les exigences réglementaires régionales ou les recommandations applicables et en vigueur, y compris
[4], [13]
celles du Code zoosanitaire international de l’OIE , doivent être prises en compte.
5 Origine
5.1 Généralités
Les paragraphes 5.2 à 5.6 et les Articles 6 à 8 doivent être appliqués par les fournisseurs de matériaux
d’origine animale, les intermédiaires et les fabricants de dispositifs médicaux, selon le cas, dans le cadre
du plan de gestion des risques conformément à l’ISO 22442-1.
La qualité du matériau d’origine animale ne doit pas être compromise par une contamination croisée
avant, pendant et après l’abattage. Les animaux doivent être certifiés comme étant propres à la
consommation humaine (voir en 5.5).
Pour le matériau d’origine animale provenant d’espèces non destinées à la consommation humaine, la
justification de l’absence d’inspection et de certification doit être documentée. Les critères de qualité
pertinents pour ce type de matériau doivent être définis par le fabricant.
Il incombe au fabricant de s’assurer que le matériau est adapté à l’usage prévu.
Les sous-produits d’origine animale non destinés à la consommation humaine doivent être des
[16]
«matériaux de catégorie 3 (c’est-à-dire sans danger) ou équivalents» .
5.2 Espèce et souche
Pour chaque matériau ou dérivé, le risque de certaines maladies dépend de l’espèce animale et
éventuellement de la souche et il faut en tenir compte lors de l’établissement des mesures de contrôle.
NOTE Des recommandations spécifiques concernant les exigences applicables au sang d’origine bovine sont
disponibles dans les «Lignes directrices sur l’utilisation de sérum bovin dans la fabrication de produits médicaux
[14]
biologiques à usage humain» .
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ISO 22442-2:2020(F)
5.3 Origine géographique
Le risque de certaines maladies dépend de l’origine géographique et il faut en tenir compte lors de
l’établissement des mesures de contrôle.
L’origine géographique peut comprendre le lieu de conception, de naissance, d’élevage et d’abattage
(pour les espèces bovines, voir l’Annexe A).
Lorsque le processus de gestion des risques l’exige, en cas d’espèces domestiquées/d’élevage, la région
géographique ou le pays de naissance et le récapitulatif des principaux lieux de résidence jusqu’à
l’abattage doivent être enregistrés.
En cas d’espèces sauvages, la région ou le lieu de capture et le pays ou la région de naissance doivent
être enregistrés s’ils sont connus. L’utilisation d’espèces de mammifères sauvages doit être traitée lors
de l’évaluation des risques (voir l’ISO 22442-1).
5.4 Inspection
La sélection du matériau d’origine animale doit faire l’objet d’un contrôle et d’une inspection
individuelle par un vétérinaire. II existe cependant certaines espèces qui ne peuvent être soumises à de
tels contrôles (par exemple les poissons, les crustacés, les cervidés, les visons, les chats). Si les animaux
ne peuvent pas être examinés individuellement, la justification de cela doit être documentée et un plan
d’échantillonnage pertinent doit être fourni.
Les espèces bovines, caprines, équines, ovines et porcines doivent être soumises à une inspection
vétérinaire ante mortem. Les animaux présentant des anomalies du système locomoteur ou des troubles
neurologiques ne doivent pas être utilisés pour la fabrication de dispositifs médicaux; dérivés du suif,
[13], [16]
noir animal et acides aminés «catégorie 3 (c’est-à-dire, sans danger) ou matériaux équivalents» .
Avant la certification, un vétérinaire doit effectuer une inspection post-mortem des espèces bovines,
caprines, ovines et porcines, des cervidés et des équidés, immédiatement après l’abattage conformément
aux coutumes et pratiques locales. L’inspection doit au moins comprendre:
a) une inspection visuelle;
b) une palpation des organes spécifiés;
c) une incision des organes et des ganglions lymphatiques;
d) la recherche d’anomalies (par exemple de consistance, de couleur et d’odeur);
e) si nécessaire, des essais en laboratoire.
Lorsque cela est indiqué par l’évaluation du risque, pour les matériaux (y compris les approvisionnements
de sang rassemblés) destinés à une utilisation directe dans des dispositifs médicaux et qui ne sont
pas soumis à un processus validé pour réduire le risque d’EST conformément à l’ISO 22442-3, il y a
lieu d’effectuer un essai biochimique validé afin de déceler la présence éventuelle d’EST chez l’animal
d’origine. Ces essais in vitro validés indiquent le statut EST positif mais ne peuvent être applicables
que pour confirmer le statut négatif d’un animal dès que cet essai est universellement accepté en tant
qu’état de l’art à cet égard.
Les tissus d’origine animale dérivés de certaines espèces (par exemple les poissons, les crustacés,
les cervidés, les visons, les chats) exigent une approche différente, car le contrôle vétérinaire ne peut
pas être effectué de la même manière que pour les autres tissus d’origine animale. Il convient que les
fabricants appliquent à ces matériaux les parties applicables du présent document, mais ils peuvent
s’appuyer sur d’autres modes opératoires dont l’efficacité de réduction des risques a été démontrée
(voir l’ISO 22442-1).
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ISO 22442-2:2020(F)
5.5 Certification
Les matériaux d’origine animale destinés à être utilisés dans des dispositifs médicaux doivent provenir
d’animaux déclarés propres à la consommation humaine par un vétérinaire. Les enregistrements
permettant de démontrer la conformité aux critères d’inspection vétérinaire à l’abattoir ainsi que
les détails du certificat et l’origine doivent être disponibles (voir par exemple l’Annexe B). En ce qui
concerne les espèces pour lesquelles une telle certification par un vétérinaire ne peut pas être établie,
un statut équivalent à «propre à la consommation humaine» est exigé, par exemple la confirmation
d’une bonne santé apparente.
5.6 Traçabilité
Lorsque la gestion des risques entreprise conformément à l’ISO 22442-1 indique qu’il est nécessaire
et réalisable, un système de traçabilité doit être établi. Il convient d’assurer de la traçabilité jusqu’à
l’abattoir ainsi que de la traçabilité par les fournisseurs de matériaux d’origine animale transformés.
L’étendue exacte de la traçabilité doit être définie par les résultats de l’évaluation du rapport bénéfices-
risques en tenant compte des systèmes d’information officiels existants.
NOTE La traçabilité peut s’avérer irréalisable si les matériaux d’origine animale sont collectés, rassemblés et
fabriqués par des fournisseurs de matériaux d’origine animale transformés.
6 Collecte
6.1 Le fabricant du dispositif médical et le fournisseur du matériau d’origine animale doivent être liés
par un cahier des charges technique définissant:
— les limites de responsabilité;
...
FINAL
INTERNATIONAL ISO/FDIS
DRAFT
STANDARD 22442-2
ISO/TC 194/SC 1
Medical devices utilizing animal
Secretariat: DIN
tissues and their derivatives —
Voting begins on:
2020-05-11
Part 2:
Voting terminates on:
Controls on sourcing, collection and
2020-07-06
handling
Dispositifs médicaux utilisant des tissus animaux et leurs dérivés —
Partie 2: Contrôles de l'origine, de la collecte et du traitement
ISO/CEN PARALLEL PROCESSING
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 SUPPOR TING
DOCUMENTATION.
IN ADDITION TO THEIR EVALUATION AS
Reference number
BEING ACCEPTABLE FOR INDUSTRIAL, TECHNO-
ISO/FDIS 22442-2:2020(E)
LOGICAL, COMMERCIAL AND USER PURPOSES,
DRAFT INTERNATIONAL STANDARDS MAY ON
OCCASION HAVE TO BE CONSIDERED IN THE
LIGHT OF THEIR POTENTIAL TO BECOME STAN-
DARDS TO WHICH REFERENCE MAY BE MADE IN
©
NATIONAL REGULATIONS. ISO 2020
---------------------- Page: 1 ----------------------
ISO/FDIS 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
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CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Fax: +41 22 749 09 47
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2020 – All rights reserved
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ISO/FDIS 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
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 .18
© ISO 2020 – All rights reserved iii
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ISO/FDIS 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 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.
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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ISO/FDIS 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.
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FINAL DRAFT INTERNATIONAL STANDARD ISO/FDIS 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 22442-1:2018, 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 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;
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ISO/FDIS 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;
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ISO/FDIS 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], [4]
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,
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.
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.
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ISO/FDIS 22442-2:2020(E)
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], [13]
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 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).
For the animal material sourced from species that are not intended for human consumption the
justification for the missing inspection and certification is to be documented. Relevant quality criteria
for this type of material are to be defined by the manufacturer.
It is the responsibility of the manufacturer to ensure that the material is fit for its intended use.
In case animal by-products not intended for human consumption are sourced, these have to be ‘Category
[16]
3 (i.e. safe) materials or equivalent’ .
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.
NOTE Specific guidance as regards requirements for bovine blood can be found in the “Guideline on the use
[14]
of bovine serum in the manufacture of human biological medicinal products” .
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 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, cervids,
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ISO/FDIS 22442-2:2020(E)
mink, cat). If individual animals cannot be inspected, the justification for this shall be documented and
a relevant sampling plan provided.
Bovine, caprine, 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; Tallow derivatives, animal charcoal, and amino acids
[13], [16]
`Category 3 (i.e. safe) materials or equivalent’ .
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. Such validated in vitro tests are indicative for TSE positive status
but can only be relied on for confirming the negative stats of an animal once such test is universally
accepted as being state of the art on this aspect.
Animal tissues derived from certain species (e.g. fish, crustaceans, cervids, mink, cat) 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 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 22442-1 indicates that it is both necessary
and feasible, a traceability system shall be established. Traceability to the slaughterhouse should
be assured, as well as traceability by suppliers of processed animal materials. The exact extent of
traceability shall be defined by the outcome of the risk-benefit assessment taking into account those
official information systems that exist.
NOTE Traceability cannot 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;
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ISO/FDIS 22442-2:2020(E)
— specifications of the material;
— documentation provided by the supplier allowing the manufacturer to meet the requirements of
this document;
— 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 be responsible for ensuring that the handling of the material is conducted
in accordance with the documented procedures.
8 Storage, transport and labelling
8.1 Collected material shall be stored and transported in closed or other appropriate containers.
8.2 The conditions for storage and transport shall not compromise compliance with the relevant
qualities of the animal material, in particular, by environmental or enzymatic degradation or microbial
proliferation.
8.3 The manufacturer shall be responsible for en
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