Biological evaluation of medical devices - Part 18: Chemical characterization of medical device materials within a risk management process (ISO 10993-18:2020)

This document specifies a framework for the identification, and if necessary, quantification of
constituents of a medical device, allowing the identification of biological hazards and the estimation
and control of biological risks from material constituents, using a generally stepwise approach to the
chemical characterization which can include one or more of the following:
— the identification of its materials of construction (medical device configuration);
— the characterization of the materials of construction via the identification and quantification of
their chemical constituents (material composition);
— the characterization of the medical device for chemical substances that were introduced during
manufacturing (e.g. mould release agents, process contaminants, sterilization residues);
— the estimation (using laboratory extraction conditions) of the potential of the medical device,
or its materials of construction, to release chemical substances under clinical use conditions
(extractables);
— the measurement of chemical substances released from a medical device under its clinical conditions
of use (leachables).
This document can also be used for chemical characterization (e.g. the identification and/or
quantification) of degradation products. Information on other aspects of degradation assessment are
covered in ISO 10993-9, ISO 10993-13, ISO 10993-14 and ISO 10993-15.
The ISO 10993 series is applicable when the material or medical device has direct or indirect body
contact (see ISO 10993-1 for categorization by nature of body contact).
This document is intended for suppliers of materials and manufacturers of medical devices, to support
a biological evaluation.

Biologische Beurteilung von Medizinprodukten - Teil 18: Chemische Charakterisierung von Werkstoffen für Medizinprodukte im Rahmen eines Risikomanagementsystems (ISO 10993-18:2020)

Dieses Dokument legt einen Rahmen für die Identifizierung und gegebenenfalls die Quantifizierung der Bestandteile eines Medizinprodukts fest, welcher die Ermittlung biologischer Gefährdungen und die Abschätzung und Beherrschung der von Bestandteilwerkstoffen ausgehenden biologischen Risiken ermöglicht. Dabei wird ein weitgehend schrittweiser Ansatz für die chemische Charakterisierung angewendet, der einen oder mehrere der folgenden Schritte umfassen kann:
- die Identifizierung der Herstellungswerkstoffe (Konfiguration des Medizinprodukts);
- die Charakterisierung der Herstellungswerkstoffe mittels Identifizierung und Quantifizierung ihrer chemischen Bestandteile (Werkstoffzusammensetzung);
- die Charakterisierung des Medizinproduktes in Bezug auf chemische Substanzen, die während der Herstellung eingeführt wurden (z. B. Formtrennmittel, herstellungsbedingte Verunreinigungen, Sterilisationsrückstände);
- die Abschätzung (unter Labor-Extraktionsbedingungen) des Potentials des Medizinprodukts oder seiner Herstellungswerkstoffe unter klinischen Gebrauchsbedingungen chemische Substanzen freizusetzen (extrahierbare Substanzen);
- die Messung der von einem Medizinprodukt unter seinen klinischen Gebrauchsbedingungen freigesetzten chemischen Substanzen (herauslösbare Substanzen).
Dieses Dokument kann auch zur chemischen Charakterisierung (z. B. zur Identifizierung und/oder Quantifizierung) von Abbauprodukten herangezogen werden. Informationen zu anderen Aspekten der Beurteilung des Abbaus werden in ISO 10993 9, ISO 10993 13, ISO 10993 14 und ISO 10993 15 behandelt.
Die Normenreihe ISO 10993 ist anwendbar, wenn der Werkstoff oder das Medizinprodukt in direkten oder indirekten Kontakt mit dem Körper kommt (zur Kategorisierung nach der Art des Körperkontakts siehe ISO 10993 1).
Dieses Dokument ist zur Unterstützung der Werkstofflieferanten und Hersteller von Medizinprodukten bei der biologischen Beurteilung vorgesehen.

Évaluation biologique des dispositifs médicaux - Partie 18: Caractérisation chimique des matériaux des dispositifs médicaux au sein d'un processus de gestion du risque (ISO 10993-18:2020)

Le présent document définit un cadre pour l'identification et, si nécessaire, la quantification des constituants d'un dispositif médical, qui permette l'identification des dangers biologiques ainsi que l'estimation et la maîtrise des risques biologiques liés aux constituants des matériaux, en utilisant une approche généralement progressive de la caractérisation chimique qui peut englober un ou plusieurs des éléments suivants:
— l'identification de ses matériaux constitutifs (configuration du dispositif médical);
— la caractérisation des matériaux constitutifs via l'identification et la quantification de leurs constituants chimiques (composition du matériau);
— la caractérisation du dispositif médical concernant les substances chimiques introduites au cours de la fabrication (par exemple, agents de démoulage, contaminants du procédé, résidus de stérilisation);
— l'estimation (dans les conditions d'extraction en laboratoire) du potentiel du dispositif médical, ou de ses matériaux constitutifs, à libérer des substances chimiques dans des conditions d'utilisation clinique (produits extractibles);
— le dosage des substances chimiques libérées par un dispositif médical dans les conditions d'utilisation clinique qui lui sont propres (produits relargables).
Le présent document peut également être utilisé pour la caractérisation chimique (par exemple, l'identification et/ou la quantification) des produits de dégradation. Les informations relatives aux autres aspects de l'appréciation de la dégradation sont fournies dans l'ISO 10993-9, ISO 10993-13, l'ISO 10993-14 et l'ISO 10993-15.
La série ISO 10993 est applicable lorsque le matériau ou le dispositif médical est en contact direct ou indirect avec le corps (voir l'ISO 10993-1 pour une catégorisation suivant la nature du contact avec le corps du patient).
Le présent document s'adresse aux fournisseurs de matériaux et aux fabricants de dispositifs médicaux, en vue d'étayer une évaluation biologique.

Biološko ovrednotenje medicinskih pripomočkov - 18. del: Kemična opredelitev lastnosti materialov za medicinske pripomočke znotraj procesov obvladovanja tveganja (ISO 10993-18:2020)

General Information

Status
Published
Public Enquiry End Date
04-Nov-2018
Publication Date
12-Oct-2020
Technical Committee
Current Stage
6060 - National Implementation/Publication (Adopted Project)
Start Date
08-Jun-2020
Due Date
13-Aug-2020
Completion Date
13-Oct-2020

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SLOVENSKI STANDARD
SIST EN ISO 10993-18:2020
01-november-2020
Nadomešča:
SIST EN ISO 10993-18:2009
Biološko ovrednotenje medicinskih pripomočkov - 18. del: Kemična opredelitev
lastnosti materialov za medicinske pripomočke znotraj procesov obvladovanja
tveganja (ISO 10993-18:2020)

Biological evaluation of medical devices - Part 18: Chemical characterization of medical

device materials within a risk management process (ISO 10993-18:2020)

Biologische Beurteilung von Medizinprodukten - Teil 18: Chemische Charakterisierung

von Werkstoffen für Medizinprodukte im Rahmen eines Risikomanagementsystems (ISO
10993-18:2020)

Évaluation biologique des dispositifs médicaux - Partie 18: Caractérisation chimique des

matériaux des dispositifs médicaux au sein d'un processus de gestion du risque (ISO

10993-18:2020)
Ta slovenski standard je istoveten z: EN ISO 10993-18:2020
ICS:
11.100.20 Biološko ovrednotenje Biological evaluation of
medicinskih pripomočkov medical devices
SIST EN ISO 10993-18:2020 en

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

---------------------- Page: 1 ----------------------
SIST EN ISO 10993-18:2020
---------------------- Page: 2 ----------------------
SIST EN ISO 10993-18:2020
EN ISO 10993-18
EUROPEAN STANDARD
NORME EUROPÉENNE
May 2020
EUROPÄISCHE NORM
ICS 11.100.20 Supersedes EN ISO 10993-18:2009
English Version
Biological evaluation of medical devices - Part 18:
Chemical characterization of medical device materials
within a risk management process (ISO 10993-18:2020)

Évaluation biologique des dispositifs médicaux - Partie Biologische Beurteilung von Medizinprodukten - Teil

18: Caractérisation chimique des matériaux des 18: Chemische Charakterisierung von Werkstoffen für

dispositifs médicaux au sein d'un processus de gestion Medizinprodukte im Rahmen eines

du risque (ISO 10993-18:2020) Risikomanagementsystems (ISO 10993-18:2020)
This European Standard was approved by CEN on 21 July 2019.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this

European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references

concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN

member.

This European Standard exists in three official versions (English, French, German). A version in any other language made by

translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management

Centre has the same status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,

Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,

Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and

United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels

© 2020 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 10993-18:2020 E

worldwide for CEN national Members.
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SIST EN ISO 10993-18:2020
EN ISO 10993-18:2020 (E)
Contents Page

European foreword ....................................................................................................................................................... 3

(informative) Relationship between this European standard and the General
Safety and Performance Requirements of Regulation (EU) 2017/745 aimed to be

covered................................................................................................................................................................ 5

(informative) Relationship between this European Standard and the essential

requirements of Directive 90/385/EEC [OJ L 189] aimed to be covered .................................... 7

(informative) Relationship between this European standard and the General
Safety and Performance Requirements of Regulation (EU) 2017/745 aimed to be

covered................................................................................................................................................................ 9

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SIST EN ISO 10993-18:2020
EN ISO 10993-18:2020 (E)
European foreword

This document (EN ISO 10993-18:2020) has been prepared by Technical Committee ISO/TC 194

"Biological and clinical evaluation of medical devices" in collaboration with Technical Committee

CEN/TC 206 “Biological and clinical evaluation of medical devices” the secretariat of which is held by

DIN.

This European Standard shall be given the status of a national standard, either by publication of an

identical text or by endorsement, at the latest by November 2020, and conflicting national standards

shall be withdrawn at the latest by November 2020.

Attention is drawn to the possibility that some of the elements of this document may be the subject of

patent rights. CEN shall not be held responsible for identifying any or all such patent rights.

This document supersedes EN ISO 10993-18:2009.

This document has been prepared under a mandate given to CEN by the European Commission and the

European Free Trade Association, and supports essential requirements of EU Directive(s).

For the relationship with EU Directive(s) see informative Annex ZA, ZB and ZC, which are an integral

part of this document.

The following referenced documents are indispensable for the application of this document. For

undated references, the latest edition of the referenced document (including any amendments) applies.

For dated references, only the edition cited applies. However, for any use of this standard ‘within the

meaning of Annex ZA’, the user should always check that any referenced document has not been

superseded and that its relevant contents can still be considered the generally acknowledged state-of-

art.

When an IEC or ISO standard is referred to in the ISO standard text, this shall be understood as a

normative reference to the corresponding EN standard, if available, and otherwise to the dated version

of the ISO or IEC standard, as listed below.

NOTE The way in which these referenced documents are cited in normative requirements determines the

extent (in whole or in part) to which they apply.

Table — Correlations between undated normative references and dated EN and ISO standards

Normative references as Equivalent dated standard
listed in Clause 2 of the
EN ISO or IEC
ISO standard
ISO 10993-1 EN ISO 10993-1:2020 ISO 10993-1:2018
ISO 10993-17 EN ISO 10993-17:2009 ISO 10993-17:2002
ISO 14971 EN ISO 14971:2020 ISO 14971:2020
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SIST EN ISO 10993-18:2020
EN ISO 10993-18:2020 (E)

According to the CEN-CENELEC Internal Regulations, the national standards organizations of the

following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,

Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,

Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of

North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the

United Kingdom.
Endorsement notice

The text of ISO 10993-18:2020 has been approved by CEN as EN ISO 10993-18:2020 without any

modification.
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SIST EN ISO 10993-18:2020
EN ISO 10993-18:2020 (E)
(informative)
Relationship between this European standard and the General Safety and
Performance Requirements of Regulation (EU) 2017/745 aimed to be
covered

This European standard has been prepared under a Commission’s standardisation request [Full

reference to the request “M/xxx”] to provide one voluntary means of conforming to the General Safety

and Performance Requirements of Regulation (EU) 2017/745 of 5 April 2017 concerning medical

devices [OJ L 117].

Once this standard is cited in the Official Journal of the European Union under that Regulation,

compliance with the normative clauses of this standard given in Table ZA.1 confers, within the limits of

the scope of this standard, a presumption of conformity with the corresponding General Safety and

Performance Requirements of that Regulation, and associated EFTA regulations.

NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk

management process needs to be in compliance with Regulation (EU) 2017/745. This means that risks have to be

‘reduced as far as possible’, ‘reduced to the lowest possible level’, ‘reduced as far as possible and appropriate’,

‘removed or reduced as far as possible’, ‘eliminated or reduced as far as possible’, ’removed or minimized as far as

possible’, or ‘minimized’, according to the wording of the corresponding General Safety and Performance

Requirement.

NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with General Safety

and Performance Requirements 1, 2, 3, 4, 5, 8, 9, 10, 11, 14, 16, 17, 18, 19, 20, 21 and 22 of the Regulation.

NOTE 3 This Annex ZA is based on normative references according to the table of references in the European

Foreword, replacing the references in the core text.

NOTE 4 When a General Safety and Performance Requirement does not appear in Table ZC.1, it means that it is

not addressed by this European Standard.
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SIST EN ISO 10993-18:2020
EN ISO 10993-18:2020 (E)
Table ZA.1 — Correspondence between this European Standard and Annex I
of Regulation (EU) 2017/745 [OJ L 117]
General Safety and
Performance Requirements of Clause(s)/sub-clause(s) of
Remarks/Notes
Regulation this EN
(EU) 2017/745
This standard provides requirements and
recommendations for the chemical
characterization of medical devices as part of
a risk management process, including a
qualitative characterization of the chemicals
and materials used, a quantitative
characterization of the amounts of chemicals
and materials used and an evaluation of
chemical release (leachable and extractable
profile) in both the design and manufacturing
processes. This chemical characterization can
10.1 a), b) and h) 5 and 6
be used to define or confirm chemical
specifications [10.1 h)] and evaluate the risk
of toxicity [10.1 a) and b)] and
biocompatibility [10.1 b)]. Flammability [10.1
a)] is not covered.
For 10.1 b), ADME (absorption, distribution,
metabolism, and excretion) is not covered. .
For 10.1 h), physical specifications are not
covered.
This standard provides requirements and
recommendations for the chemical
characterization of medical devices as part of
a risk management process, including an
evaluation of the release of contaminants and
10.2 5 and 6
residues (composition, leachable and
extractable profile) in both the design and
manufacturing processes. Packaging is not
covered. Aspects of contaminants and residues
during transport and storage are not covered.
This standard provides requirements and
recommendations for the chemical
characterization of medical devices as part of
a risk management process, including an
evaluation of chemical substances that may
10.4.1 (First paragraph, first sentence) 5 and 6
be released from the medical device
(composition, leachable and extractable
profile) in both the design and manufacturing
processes.
Particles and wear debris are not covered.

WARNING 1: Presumption of conformity stays valid only as long as a reference to this European

standard is maintained in the list published in the Official Journal of the European Union. Users of this

standard should consult frequently the latest list published in the Official Journal of the European

Union.

WARNING 2: Other Union legislation may be applicable to the product(s) falling within the scope of this

standard.
---------------------- Page: 8 ----------------------
SIST EN ISO 10993-18:2020
EN ISO 10993-18:2020 (E)
(informative)
Relationship between this European Standard and the essential
requirements of Directive 90/385/EEC [OJ L 189] aimed to be covered

This European Standard has been prepared under a Commission’s joint standardization request

M/BC/CEN/89/9 concerning harmonized standards relating to horizontal aspects in the field of medical

devices to provide one voluntary means of conforming to essential requirements of Council Directive

90/385/EEC of 20 June 1990 on the approximation of the laws of the Member States relating to active

implantable medical devices [OJ L 189].

Once this standard is cited in the Official Journal of the European Union under that Directive,

compliance with the normative clauses of this standard given in Table ZB.1 confers, within the limits of

the scope of this standard, a presumption of conformity with the corresponding essential requirements

of that Directive and associated EFTA regulations.

NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk

management process needs to be in compliance with Directive 90/385/EEC as amended by 2007/47/EC. This

means that risks have to be reduced ‘as far as possible’, ‘to a minimum’, ‘to the lowest possible level’, ‘minimized’

or ‘removed’, according to the wording of the corresponding essential requirement.

NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with Essential

Requirements 1, 4, 5, 8, 9 and 10 of the Directive.

NOTE 3 This Annex ZB is based on normative references according to the table of references in the European

foreword, replacing the references in the core text.

NOTE 4 When an Essential Requirement does not appear in Table ZB.1, it means that it is not addressed by this

European Standard.
---------------------- Page: 9 ----------------------
SIST EN ISO 10993-18:2020
EN ISO 10993-18:2020 (E)

Table ZB.1 — Correspondence between this European Standard and Annex I of Directive

90/385/EEC [OJ L 189]
Essential Requirements of Clause(s)/sub-clause(s) Remarks/Notes
Directive 90/385/EEC of this EN
This standard provides
requirements and recommendations
for evaluating the chemical
characterization of medical devices
as part of a risk management
process, including a qualitative
characterization of the chemicals
and materials used, a quantitative
9 (only first and second characterization of the amounts of
5 and 6
indent) chemicals and materials used and
an evaluation of chemical release
(leachable and extractable profile)
in both the design and
manufacturing processes. This
chemical characterization can be
used to evaluate the risk of toxicity
(first indent) and biocompatibility
(second indent).

General Note: Presumption of conformity depends on also complying with the relevant parts of the

ISO 10993 series.

WARNING 1 — Presumption of conformity stays valid only as long as a reference to this European

Standard is maintained in the list published in the Official Journal of the European Union. Users of this

standard should consult frequently the latest list published in the Official Journal of the European

Union.

WARNING 2 — Other Union legislation may be applicable to the products falling within the scope of

this standard.
---------------------- Page: 10 ----------------------
SIST EN ISO 10993-18:2020
EN ISO 10993-18:2020 (E)
(informative)
Relationship between this European standard and the General Safety and
Performance Requirements of Regulation (EU) 2017/745 aimed to be
covered

This European standard has been prepared under a Commission’s standardisation request [Full

reference to the request “M/xxx”] to provide one voluntary means of conforming to the General Safety

and Performance Requirements of Regulation (EU) 2017/745 of 5 April 2017 concerning medical

devices [OJ L 117].

Once this standard is cited in the Official Journal of the European Union under that Regulation,

compliance with the normative clauses of this standard given in Table ZC.1 confers, within the limits of

the scope of this standard, a presumption of conformity with the corresponding General Safety and

Performance Requirements of that Regulation, and associated EFTA regulations.

NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk

management process needs to be in compliance with Regulation (EU) 2017/745. This means that risks have to be

‘reduced as far as possible’, ‘reduced to the lowest possible level’, ‘reduced as far as possible and appropriate’,

‘removed or reduced as far as possible’, ‘eliminated or reduced as far as possible’, ’removed or minimized as far as

possible’, or ‘minimized’, according to the wording of the corresponding General Safety and Performance

Requirement.

NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with General Safety

and Performance Requirements 1, 2, 3, 4, 5, 8, 9, 10, 11, 14, 16, 17, 18, 19, 20, 21 and 22 of the Regulation.

NOTE 3 This Annex ZC is based on normative references according to the table of references in the European

Foreword, replacing the references in the core text.

NOTE 4 When a General Safety and Performance Requirement does not appear in Table ZC.1, it means that it is

not addressed by this European Standard.
---------------------- Page: 11 ----------------------
SIST EN ISO 10993-18:2020
EN ISO 10993-18:2020 (E)

Table ZC.1 — Correspondence between this European Standard and Annex I of Regulation (EU)

2017/745 [OJ L 117]
General Safety and
Performance Requirements of Clause(s)/sub-clause(s) of
Remarks/Notes
Regulation this EN
(EU) 2017/745
This standard provides requirements and
recommendations for the chemical
characterization of medical devices as part of a
risk management process, including a
qualitative characterization of the chemicals
and materials used, a quantitative
characterization of the amounts of chemicals
and materials used and an evaluation of
chemical release (leachable and extractable
profile) in both the design and manufacturing
processes. This chemical characterization can
10.1 a), b) and h) 5 and 6
be used to define or confirm chemical
specifications [10.1 h)] and evaluate the risk of
toxicity [10.1 a) and b)] and biocompatibility
[10.1 b)]. Flammability [10.1 a)] is not covered.
For 10.1 b), ADME (absorption, distribution,
metabolism, and excretion) is not covered. .
For 10.1 h), physical specifications are not
covered.
This standard provides requirements and
recommendations for the chemical
characterization of medical devices as part of a
risk management process, including an
evaluation of the release of contaminants and
10.2 5 and 6
residues (composition, leachable and
extractable profile) in both the design and
manufacturing processes. Packaging is not
covered. Aspects of contaminants and residues
during transport and storage are not covered.
This standard provides requirements and
recommendations for the chemical
characterization of medical devices as part of a
risk management process, including an
10.4.1 (First paragraph, first
evaluation of chemical substances that may be
5 and 6
sentence)
released from the medical device (composition,
leachable and extractable profile) in both the
design and manufacturing processes.
Particles and wear debris are not covered.

General Note: Presumption of conformity depends on also complying with the relevant parts of the

ISO 10993 series.

WARNING 1 — Presumption of conformity stays valid only as long as a reference to this European

standard is maintained in the list published in the Official Journal of the European Union. Users of this

standard should consult frequently the latest list published in the Official Journal of the European

Union.

WARNING 2 — Other Union legislation may be applicable to the product(s) falling within the scope of

this standard.
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SIST EN ISO 10993-18:2020
INTERNATIONAL ISO
STANDARD 10993-18
Second edition
2020-01
Biological evaluation of medical
devices —
Part 18:
Chemical characterization of medical
device materials within a risk
management process
Évaluation biologique des dispositifs médicaux —
Partie 18: Caractérisation chimique des matériaux des dispositifs
médicaux au sein d'un processus de gestion du risque
Reference number
ISO 10993-18:2020(E)
ISO 2020
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SIST EN ISO 10993-18:2020
ISO 10993-18:2020(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.
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Email: copyright@iso.org
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Published in Switzerland
ii © ISO 2020 – All rights reserved
---------------------- Page: 14 ----------------------
SIST EN ISO 10993-18:2020
ISO 10993-18:2020(E)
Contents Page

Foreword ........................................................................................................................................................................................................................................iv

Introduction ..................................................................................................................................................................................................................................v

1 Scope ................................................................................................................................................................................................................................. 1

2 Normative references ...................................................................................................................................................................................... 1

3 Terms and definitions ..................................................................................................................................................................................... 2

4 Symbols and abbreviated terms ........................................................................................................................................................... 6

5 Characterization procedure ...................................................................................................................................................................... 7

5.1 General ........................................................................................................................................................................................................... 7

5.2 Establish medical device configuration and material composition .......................................................10

5.2.1 General...................................................................................................................................................................................10

5.2.2 Information gathering ..............................................................................................................................................11

5.2.3 Information generation ...........................................................................................................................................11

5.3 Assess material/chemical equivalence to a clinically established material or

medical device ......................................................................................................................................................................................12

5.4 Assess the hypothetical worst-case chemical release based on total exposure to

the medical device’s chemical constituents ................................................................................................................13

5.4.1 Establish the hypothetical worst-case chemical release ............................................................13

5.4.2 Assess the hypothetical worst-case chemical release ..................................................................13

5.5 Establish an analytical evaluation threshold .............................................................................................................14

5.6 Estimate the chemical release; perform extraction study ..............................................................................14

5.7 Assess the estimated chemical release (extractables profile) ....................................................................17

5.8 Determine the actual chemical release; perform leachables study ........................................................17

5.9 Assess the actual chemical release (leachables profile) ...................................................................................19

5.10 Exiting the chemical characterization process .........................................................................................................19

6 Chemical characterization parameters and methods .................................................................................................19

6.1 General ........................................................................................................................................................................................................19

6.2 Material composition .....................................................................................................................................................................20

6.3 Extractables and leachables .....................................................................................................................................................22

6.4 Structural composition or configuration .......................................................................................................................24

6.5 Analytical methods ...........................................................................................................................................................................25

7 Reporting of the chemical characterization data ............................................................................................................26

Annex A (informative) General principles of chemical characterization ....................................................................27

Annex B (informative) Information sources for chemical characterization ............................................................31

Annex C (informative) Principles for establishing biological equivalence ................................................................35

Annex D (informative) Principles of sample extraction ................................................................................................................38

Annex E (informative) Calculation and application of the analytical evaluation threshold (AET) ...50

Annex F (informative) Qualification of analytical methods used for extractables/leachables ............58

Annex G (informative) Reporting details for analytical methods and chemical data .....................................61

Bibliography .............................................................................................................................................................................................................................64

© ISO 2020 – All rights reserved iii
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SIST EN ISO 10993-18:2020
ISO 10993-18:2020(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 declara
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