oSIST prEN ISO 22442-2:2019

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

Dispositifs médicaux utilisant des tissus animaux et leurs dérivés - Partie 2: Contrôles de

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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

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

(EU) No 722/2012 ............................................................................................................................................................................................15

Bibliography .............................................................................................................................................................................................................................17

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

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

Any trade name used in this document is information given for the convenience of users and does not

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

This third edition cancels and replaces the second edition (ISO 22442-2:2015), of which it constitutes a

— 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;

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

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

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

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

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.

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

For the purposes of this document, the terms and definitions given in ISO/DIS 22442-1 and the

ISO and IEC maintain terminological databases for use in standardization at the following addresses:

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:

g) a process to control introduction of genetic material from herds with the deviating TSE status

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

Note 1 to entry: Under certain jurisdictions, it is a requirement that the veterinarian be a professionally qualified

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

Apply the requirements of this document as determined by the risk assessment (see ISO/DIS 22442-1).

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

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,

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

b) hygiene and quality assurance requirements to be met by the slaughterer including the provisions

c) procedures for the collection, preservation, handling, storage, and transport of materials of

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

Manufacturers should apply relevant provisions of ISO 22442 to natural substances such as milk, hair,

NOTE 2 The use of risk analysis/risk management tools [such as HACCP, FMEA (see ISO 14971:2007, Annex G)]

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

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

a) the pertinent issues of appropriate documents are available at all locations where operations

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

Where practicable, the nature of each change shall be identified in the document or the appropriate

A master list or equivalent document control procedure shall be established to identify the current

Responsibility for the collection, handling, and storage of materials shall be assigned to qualified

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

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

The manufacturer shall identify the in-house verification requirements and shall provide adequate

Audits shall be carried out by personnel independent of those having direct responsibility for the work

Due account shall be taken of relevant current regional regulatory requirements or guidance including

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/

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.

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.

The risk of certain diseases is dependent on the geographical origin and this shall be taken into account

Geographical origin can include conception, birth, rearing, and slaughtering (for bovine species, see

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

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

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

individual animals cannot be inspected, the justification for this shall be documented and a relevant

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

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

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

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).

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.

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

6.1 Between the manufacturer of the medical device and the supplier of material of animal origin,

— 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

6.2 The manufacturer shall be responsible for ensuring that the collection of the material is conducted

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

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

7.2 Source materials to be utilized in medical devices shall be segregated for delivery according to a