SIST EN 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)

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: Withdrawn
• Public Enquiry End Date: 04-Nov-2018
• Publication Date: 12-Oct-2020
• Withdrawal Date: 13-Sep-2023
• ICS: 11.100.20 - Biological evaluation of medical devices
• Technical Committee: VAZ - Healthcare
• Current Stage: 9900 - Withdrawal (Adopted Project)
• Start Date: 24-Aug-2023
• Due Date: 16-Sep-2023
• Completion Date: 14-Sep-2023
• Directive: 2007/47/EC - Directive 2007/47/EC of the European Parliament and of the council of 5 September 2007 amending Council Directive 90/385/EEC on the approximation of the laws of the Member States relating to active implantable medical devices, Council Directive 93/42/EEC concerning medical devices and Directive 98/8/EC concerning the placing of biocidal products on the market
• Directive: 90/385/EEC - 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
• Directive: 93/42/EEC - Council Directive 93/42/EEC of 14 June 1993 concerning medical devices
• Mandate: M/BC/CEN/89/9 - Joint Standardization request to CEN/CENELEC concerning harmonized standards relating to horizontal aspects in the field of medical devices
• Ref Project: EN 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)

Relations

• Replaces: SIST EN ISO 10993-18:2009 - Biological evaluation of medical devices - Part 18: Chemical characterization of materials (ISO 10993-18:2005)
• Effective Date: 01-Nov-2020
• Amended By: SIST EN ISO 10993-18:2020/A1:2023 - Biological evaluation of medical devices - Part 18: Chemical characterization of medical device materials within a risk management process - Amendment 1: Determination of the uncertainty factor (ISO 10993-18:2020/Amd 1:2022)
• Effective Date: 16-Jun-2021

Standards Content (Sample)

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.

---------------------- Page: 3 ----------------------
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

2

---------------------- Page: 4 ----------------------
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

3

---------------------- Page: 5 ----------------------
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.

4

---------------------- Page: 6 ----------------------
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.
5

---------------------- Page: 7 ----------------------
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.
6

---------------------- 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.
7

---------------------- 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.
8

---------------------- 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.
9

---------------------- 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.

10

---------------------- Page: 12 ----------------------
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

---------------------- Page: 13 ----------------------
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.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: [phone]
Fax: [phone]
Email: [e-mail]
Website: www.iso.org
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

---------------------- Page: 15 ----------------------
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
...

SLOVENSKI STANDARD
oSIST prEN ISO 10993-18:2018
01-november-2018
%LRORãNRRYUHGQRWHQMHPHGLFLQVNLKSULSRPRþNRYGHO.HPLþQDRSUHGHOLWHY
ODVWQRVWLPDWHULDORY]QRWUDMSURFHVRYREYODGRYDQMDWYHJDQMD,62',6

Biological evaluation of medical devices - Part 18: Chemical characterization of medical
device materials within a risk management process - Évaluation biologique (ISO/DIS
10993-18:2018)
Biologische Beurteilung von Medizinprodukten - Teil 18: Chemische Charakterisierung
von Werkstoffen für Medizinprodukte im Rahmen eines Risikomanagementsystems
(ISO/DIS 10993-18:2018)
Évaluation biologique des dispositifs médicaux - Partie 18: Caractérisation chimique des
matériaux des dispositifs médicaux au sein d'un processus de gestion du risque
(ISO/DIS 10993-18:2018)
Ta slovenski standard je istoveten z: prEN ISO 10993-18
ICS:
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
oSIST prEN ISO 10993-18:2018 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

---------------------- Page: 1 ----------------------
oSIST prEN ISO 10993-18:2018

---------------------- Page: 2 ----------------------
oSIST prEN ISO 10993-18:2018
DRAFT INTERNATIONAL STANDARD
ISO/DIS 10993-18
ISO/TC 194 Secretariat: DIN
Voting begins on: Voting terminates on:
2018-08-08 2018-10-31
Biological evaluation of medical devices —
Part 18:
Chemical characterization of medical device materials
within a risk management process — Évaluation
biologique
Évaluation biologique des dispositifs médicaux —
Partie 18: Caractérisation chimique des matériaux des dispositifs médicaux au sein d'un processus de
gestion du risque
ICS: 11.100.20
THIS DOCUMENT IS A DRAFT CIRCULATED
This document is circulated as received from the committee secretariat.
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
IN ADDITION TO THEIR EVALUATION AS
ISO/CEN PARALLEL PROCESSING
BEING ACCEPTABLE FOR INDUSTRIAL,
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
STANDARDS MAY ON OCCASION HAVE TO
BE CONSIDERED IN THE LIGHT OF THEIR
POTENTIAL TO BECOME STANDARDS TO
WHICH REFERENCE MAY BE MADE IN
Reference number
NATIONAL REGULATIONS.
ISO/DIS 10993-18:2018(E)
RECIPIENTS OF THIS DRAFT ARE INVITED
TO SUBMIT, WITH THEIR COMMENTS,
NOTIFICATION OF ANY RELEVANT PATENT
RIGHTS OF WHICH THEY ARE AWARE AND TO
©
PROVIDE SUPPORTING DOCUMENTATION. ISO 2018

---------------------- Page: 3 ----------------------
oSIST prEN ISO 10993-18:2018
ISO/DIS 10993-18:2018(E)

COPYRIGHT PROTECTED DOCUMENT
© ISO 2018
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting
on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address
below or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: [phone]
Fax: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland
ii © ISO 2018 – All rights reserved

---------------------- Page: 4 ----------------------
oSIST prEN ISO 10993-18:2018
ISO/DIS 10993-18:2018(E)

Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Symbols and abbreviated terms . 5
5 Characterization procedure . 6
5.1 General . 6
5.2 Address contact with a potentially affected individual . 10
5.2.1 Establish contact with a potentially affected individual . 10
5.2.2 Assess contact with a potentially affected individual . 10
5.3 Establish medical device configuration and material composition . 10
5.3.1 General.10
5.3.2 Information gathering . 11
5.3.3 Information generation . 11
5.4 Assess versus a clinically established material or medical device . 12
5.5 Establish appropriate safety threshold . 13
5.6 Assess the hypothetical worst case chemical release based on total exposure to the
medical device’s chemical constituents . 13
5.6.1 Establish the greatest potential chemical release . 13
5.6.2 Assess the greatest potential chemical release . 13
5.7 Estimate the medical device’s actual chemical release; perform extraction study . 14
5.8 Assess the medical device’s estimated chemical release (extractables profile) . 16
5.8.1 Perform the risk assessment . 16
5.8.2 Evaluate results of the risk assessment . 16
5.9 Determine the medical device’s actual chemical release; perform leachables study . 16
5.10 Assess the medical device’s actual chemical release (leachables profile) . 18
5.10.1 Perform the risk assessment . 18
5.10.2 Evaluate results of the risk assessment . 18
5.11 Exiting the chemical characterization process . 18
5.11.1 Medical device presents an acceptable health risk . 18
5.11.2 Medical device presents a potential health risk . 18
6 Chemical characterization parameters and methods .18
6.1 General .18
6.2 Chemical composition . 19
6.3 Extractables and leachables . 20
6.4 Structural composition or configuration . 22
6.5 Analytical methods . 23
7 Reporting of the chemical and/or compositional 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 .37
Annex E (informative) Calculation and application of the analytical evaluation threshold (AET) .48
Annex F (informative) Reporting details for analytical methods and chemical data .53
ANNEX ZA (informative) Relationship between this European Standard and the essential
requirements of Directive 93/42/EEC [OJ L 169] aimed to be covered .57
© ISO 2018 – All rights reserved iii

---------------------- Page: 5 ----------------------
oSIST prEN ISO 10993-18:2018
ISO/DIS 10993-18:2018(E)

Annex ZB (informative) Relationship between this European Standard and the essential
requirements of Directive 90/385/EEC [OJ L 189] aimed to be covered .59
Bibliography .61
iv © ISO 2018 – All rights reserved

---------------------- Page: 6 ----------------------
oSIST prEN ISO 10993-18:2018
ISO/DIS 10993-18:2018(E)

Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www .iso .org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to the
World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see the following
URL: www .iso .org/iso/foreword .html.
This document was prepared by Technical Committee ISO/TC 194, Biological and clinical evaluation of
medical devices.
This second edition cancels and replaces the first edition (ISO 10993-18:2005), which has been
technically revised.
The main changes compared to the previous edition are as follows:
a) greater integration and harmonization with ISO 10993-1, ISO 10993-12, and ISO 10993-17;
b) a revised and expanded chemical characterization process flowchart;
c) a strengthened explanation that analytical testing is not necessarily required;
d) added a number of definitions (e.g., medical device configuration, materials of construction,
material composition);
e) clarified testing approaches unique to material characterization (i.e., digestion and dissolution for
hazard identification);
f) added discussion of considerations related to analytical method qualification;
g) added informative annexes on general principles, vehicle extraction considerations, and the
analytical evaluation threshold (AET; concentration threshold below which extractables or
leachables identification is unneeded).
A list of all parts in the ISO 10993 series can be found on the ISO website.
© ISO 2018 – All rights reserved v

---------------------- Page: 7 ----------------------
oSIST prEN ISO 10993-18:2018
ISO/DIS 10993-18:2018(E)

Introduction
ISO 10993-1 serves as a framework in which to plan a biological evaluation which, as scientific
knowledge advances our understanding of the basic mechanisms of tissue responses, minimizes
the number and exposure of test animals by giving preference to assessment of chemical/physical
properties and testing with in vitro models in situations within a risk assessment process where these
methods yield equally relevant information to that obtained from in vivo models.
The characterization procedure and its associated flowchart is based on the principles in ISO 10993-1;
specifically, that the biological evaluation and toxicological risk assessment process is most efficient
and effective if it is based on the minimum amount of acceptable and necessary chemical information
that can establish that a medical device presents an acceptable health risk.
ISO 10993-1, Clause 4 states that in the selection of materials to be used in medical device manufacture,
the first consideration shall be fitness for purpose with regard to characteristics and properties of the
material, which can include chemical, toxicological, physical, electrical, morphological and mechanical
properties. This information is necessary for any biological evaluation. Furthermore, IS0 10993-1, 6.1
states that material characterization is a crucial first step in the biological evaluation process and
includes a discussion of the role and application of chemical characterization in risk assessment.
Lastly, ISO 10993-1, and by reference ISO 14971, points out that a toxicological risk analysis should take
into account the chemical nature of the medical device, its material composition, and its intended use.
The requirements specified in this document are intended to yield the following information, which
will be of value in assessing the biological response of the materials as represented in the final product.
— The identities and quantities, as appropriate, of the materials of construction of the medical device
(device configuration).
— The identities and quantities, as appropriate, of the chemical constituents in each material of
construction (material composition).
— The identities and quantities, as appropriate, of chemical substances used in the medical device’s
manufacturing process including processing aids and residues.
— The potential of the medical device and/or its materials of construction to release chemical substances
to which a potentially affected individual could be exposed to during clinical conditions of use.
The chemical composition of the materials of construction is mainly established by the suppliers of
these materials. The chemical composition may change during manufacture of a medical device. Other
medical device characteristics are chiefly established by component suppliers or device manufacturers
to address the performance and quality requirements to be met by the finished medical device as well
as the production, storage and distribution processes experienced by the medical device.
vi © ISO 2018 – All rights reserved

---------------------- Page: 8 ----------------------
oSIST prEN ISO 10993-18:2018
DRAFT INTERNATIONAL STANDARD ISO/DIS 10993-18:2018(E)
Biological evaluation of medical devices —
Part 18:
Chemical characterization of medical device materials
within a risk management process — Évaluation
biologique
1 Scope
This document specifies a framework for the identification of biological hazards and the estimation and
control of biological risks from material constituents, using a stepwise approach to the characterization
of a medical device through:
— 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);
— the estimation 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 may 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 of standards 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.
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated
references, the latest edition of the referenced document (including any amendments) applies.
ISO 10993-1:2018, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
ISO 10993-12:2012, Biological evaluation of medical devices — Part 12: Sample preparation and reference
materials
ISO 10993-17, Biological evaluation of medical devices — Part 17: Establishment of allowable limits for
leachable substances
ISO 14971, Medical devices — Application of risk management to medical devices
© ISO 2018 – All rights reserved 1

---------------------- Page: 9 ----------------------
oSIST prEN ISO 10993-18:2018
ISO/DIS 10993-18:2018(E)

3 Terms and definitions
For the purposes of this document, the definitions in ISO 10993-1 and the following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— IEC Electropedia: available from http: //www .electropedia .org/
— ISO Online browsing platform: available from http: //www .iso .org/obp
3.1
accelerated extraction
extraction whose duration is shorter than the duration of clinical use but whose conditions do not result
in a chemical change to the substances being extracted
Note 1 to entry: See also Annex D.
3.2
analytical evaluation threshold (AET)
threshold below which the analyst need not identify or quantify leachables or extractables or report
them for potential toxicological assessment (see Annex E)
3.3
analytically expedient
situation where an extraction vehicle can be directly evaluated with generally available analytical
methods with the sensitivity and selectivity necessary to achieve a designated reporting threshold
such as the AET
3.4
analytical screening method
method whose purpose is to discover, identify and semi-quantitatively estimate the concentration of all
relevant analytes in a test sample above an established reporting threshold (such as the AET)
3.5
analytical targeting method
method whose purpose is to quantify, with an appropriately high degree of accuracy and precision,
specified analytes in a specified test sample over a specified concentration range
3.6
chemical characterization
process of obtaining chemical information, accomplished by either information gathering or by
information generation, for example, by chemical testing
3.7
chemical information
qualitative and quantitative knowledge related to the configuration, composition and production of the
medical device and/or its materials of construction, thereby establishing the identities and levels of
chemicals present in the materials and device (including any additives and processing aids)
Note 1 to entry: See also 5.3.1, 5.3.2, 5.3.3, and Annex B.
Note 2 to entry: Chemical information can be used to establish the hypothetical worst case release of chemicals
from a medical device, predicated on the circumstance that all chemicals present in the device are released from
the device under its clinical conditions of use.
3.8
clinically established material, component or medical device
medical device (and its associated materials and components of construction) which has been used
extensively for specified and established clinical uses for which biocompatibility has been established
2 © ISO 2018 – All rights reserved

---------------------- Page: 10 ----------------------
oSIST prEN ISO 10993-18:2018
ISO/DIS 10993-18:2018(E)

3.9
component
item which is manufactured from a basic starting material but is not itself a medical device, since it
forms only one part of a medical device
3.10
constituent
chemical that is present in a finished medical device or its materials of construction
Note 1 to entry: Constituents may be intentionally present (e.g., an additive such as an antioxidant) or
unintentionally present (e.g., an impurity).
3.11
convertor
person or company who converts or fabricates a basic raw material into a semi-finished product (e.g. a
former of lengths of rod, tubing, or plastic components)
3.12
digestion
process of solubilizing a medical device, one or more of its components or one or more of its materials
of construction by breaking it down into its fundamental structural units, including its elemental
constituents or monomeric units
3.13
dissolution
process of completely solubilizing a medical device, one or more of its components and /or one or more
of its materials of construction, generally preserving the molecular structures of its constituents
3.14
exaggerated extraction
extraction that is intended to result in a greater number or amount of chemical constituents being
released as compared to the amount generated under the clinical conditions of use but is not expected
to result in a chemical change of the substances being extracted
3.15
exhaustive extraction
a multi-step extraction conducted until the amount of material extracted in a subsequent extraction
step is less than 10 % by gravimetric analysis (or achieved by other means) of that determined in the
first extraction step
3.16
extractables
substances that are released from a medical device or material of construction when the medical device
or material is extracted using laboratory extraction conditions and vehicles
3.17
extraction
process performed to separate a chemical substance from a test article by exposing the test article to
an extraction vehicle under defined and controlled conditions
3.18
extraction power
ability of an extraction vehicle to extract (or leach) substances from a medical device, component or
material of construction
Note 1 to entry: The extraction power of an extraction vehicle is impacted by its physicochemical properties,
including, but not limited to, its polarity, pH, volatility, permeability, dielectric constant.
© ISO 2018 – All rights reserved 3

---------------------- Page: 11 ----------------------
oSIST prEN ISO 10993-18:2018
ISO/DIS 10993-18:2018(E)

3.19
extraction vehicle
that medium (solution or solvent) which is used to extract (or leach) a test article for the purpose of
establishing the test article’s extractables or leachables profile
Note 1 to entry: For some medical devices (e.g., infusion systems) that are labelled for use with a drug, the most
appropriate extraction medium may be the drug product or drug product vehicle.
Note 2 to entry: It is preferred that extraction vehicles be analytically expedient.
3.20
identification
process of assigning a molecular structure and chemical name to an organic compound or assigning
constituent elements or molecular structure as appropriate, and a chemical name to an inorganic
compound
3.21
information gathering
process of collecting existing chemical information, including available test results, that is relevant to
chemical characterization
3.22
information generation
process of producing chemical information via laboratory testing
3.23
leachables
substances that are released from a medical device and to a potentially affected individual during its
clinical use
Note 1 to entry: Leachables studies establish the type and amount of compounds that are released from a device
under its actual conditions of clinical use.
3.24
manufacturer
natural or legal person who manufactures or fully refurbishes a medical device, or has a device designed,
manufactured, or fully refurbished, and markets that medical device under its name or trademark
3.25
material composition
listing of the substances that are contained in a material (qualitative) and the amount of each substance
in the material (quantitative)
Note 1 to entry: A material’s composition establishes the hypothetical situation in which the total amount of all
substances present in a medical device are released during clinical use. These amounts can be derived directly
from known composition; experimentally, they can be derived from digestion, dissolution, and, in many cases,
exhaustive extraction studies.
3.26
material of construction
individual raw materials (for example, polymer resins) that are used to produce a component
3.27
medical device configuration
listing of a medical device’s components (qualitative), including a listing of the component’s materials of
construction (qualitative) and the proportion of each material in each component (quantitative)
3.28
potentially affected individual
person having direct or indirect body contact with the medical device (see ISO 10993-1 for categorization
by nature of body contact)
4 © ISO 2018 – All rights reserved

---------------------- Page: 12 ----------------------
oSIST prEN ISO 10993-18:2018
ISO/DIS 10993-18:2018(E)

3.29
safety concern threshold (SCT)
conceptually derived and information-based dose threshold below which a leachable (or an extractable
as a probable leachable) has a dose so low that it presents a negligible safety concern from carcinogenic
and non-carcinogenic toxic effects
3.30
simulated-use extraction
extraction, performed using an extraction method that simulates clinical use, which is conducted to
evaluate those extractable substances which could be available as leachables from a medical device
during the routine clinical use of the device
Note 1 to entry: A simulated-use extraction is performed to estimate the type and amount of substances that
are expected to be released from a medical device during its clinical use. A simulated-use extraction is designed
to produce an extractables profile that represents the worst case leachables profile, meaning that all leachables
are also extractables and the levels of all individual extractables are at least equal to the level of all individual
leachables.
3.31
solubilisation
action or process of using a vehicle to dissolve part or all of a test article
Note 1 to entry: Leaching, extraction, dissolution, and digestion are (progressively more complete) sub-
categories of solubilisation.
3.32
sponsor
individual or organization that plans, commissions, and takes responsibility for testing of a medical device
3.33
supplier
person or company who manufactures and/or supplies the basic starting materials of construction to
be used in the manufacture of a medical device
3.34
threshold of toxicological concern (TTC)
theoretically derived human exposure threshold value for all chemicals (except for known and
documented exclusions) below which the chemical would not pose an appreciable risk to human health
as established by relevant and appropriate biological endpoints
3.35
toxicological risk assessment
act of determining the potential of a chemical to elicit an adverse effect based on a specified level of
exposure
4 Symbols and abbreviated terms
The abbreviated terms given in Table 1 are used in this document.
Table 1 — Methodology abbreviations
Abbreviated term Analytic
...