EN ISO 10993-17:2023
(Main)Biological evaluation of medical devices - Part 17: Toxicological risk assessment of medical device constituents (ISO 10993-17:2023)
Biological evaluation of medical devices - Part 17: Toxicological risk assessment of medical device constituents (ISO 10993-17:2023)
This document specifies the process and requirements for the toxicological risk assessment of medical device constituents. The methods and criteria used to assess whether exposure to a constituent is without appreciable harm are also specified. The toxicological risk assessment can be part of the biological evaluation of the final product, as described in ISO 10993-1.
The process described in this document applies to chemical characterization information obtained in line with ISO 10993-18. When a toxicological risk assessment of either the compositional information or analytical chemistry data (e.g. extractable data or leachable data) are required to determine whether the toxicological risks related to the constituents are negligible or tolerable.
The process described in this document is not intended to apply to circumstances where the toxicological risk has been estimated by other means, such as:
— constituents, excluding cohort of concern or excluded chemicals, that are present in or extracted from a medical device at an amount representative of patient exposure below a relevant, toxicologically-based reporting threshold (see applicable requirements in ISO 10993-18:2020, Annex E and ISO/TS 21726);
— a new or changed medical device for which chemical or biological equivalence has been established with an existing biocompatible or clinically established medical device (see applicable requirements in ISO 10993-18:2020, Annex C).
The process described in this document is also not applicable to:
— medical device constituents that do not contact the body (e.g. in vitro diagnostics);
— biological risks associated with physical interactions of the medical device with the body (i.e. application of mechanical forces, energy or surface morphology, etc.), provided that the chemical exposure is not changed;
— active pharmaceutical ingredients of device-drug combination products or biologic components of device-biologic combination products as additional regulatory considerations can apply;
— exposure to a particular constituent that arises from sources other than the device, such as food, water or air.
Biologische Beurteilung von Medizinprodukten - Teil 17: Toxikologische Risikobewertung von Medizinproduktbestandteilen (ISO 10993-17:2023)
Dieses Dokument legt das Verfahren und die Anforderungen für die Bewertung des toxikologischen Risikos von Bestandteilen von Medizinprodukten fest. Darüber hinaus werden Verfahren und Kriterien zur Bewertung, ob die Exposition gegenüber einem Bestandteil ohne nennenswerten Schaden bleibt, festgelegt. Die Bewertung des toxikologischen Risikos kann Teil der biologischen Beurteilung des Endprodukts sein, wie in ISO 10993 1 beschrieben.
Das in diesem Dokument beschriebene Verfahren ist anwendbar auf die Informationen über die chemische Charakterisierung, die nach ISO 10993 18 erhalten wurden. Wenn eine Bewertung des toxikologischen Risikos entweder der Informationen zur Zusammensetzung oder der Daten aus der analytischen Chemie (z. B. Daten zu den extrahierbaren oder herauslösbaren Substanzen) erforderlich ist, um festzustellen, ob die toxikologischen Risiken in Verbindung mit den Bestandteilen vernachlässigbar oder tolerierbar sind.
Das in diesem Dokument beschriebene Verfahren ist nicht für Fälle vorgesehen, in denen das toxikologische Risiko auf andere Weise geschätzt wurde, wie z. B.:
Bestandteile, mit Ausnahme der Kohorte bedenklicher Stoffe oder ausgeschlossener Chemikalien, die in einer für die Patientenexposition repräsentativen Menge unterhalb einer relevanten, toxikologisch begründeten Berichtsschwelle in einem Medizinprodukt vorhanden oder aus ihm extrahierbar sind (siehe anwendbare Anforderungen in ISO 10993 18:2020, Anhang E und ISO/TS 21726);
ein neues oder geändertes Medizinprodukt, für das die chemische oder biologische Gleichwertigkeit mit einem vorhandenen biokompatiblen oder klinisch etablierten Medizinprodukt festgestellt wurde (siehe anwendbare Anforderungen in ISO 10993 18:2020, Anhang C).
Außerdem ist das in diesem Dokument beschriebene Verfahren nicht anwendbar auf:
Bestandteile von Medizinprodukten, die nicht mit dem Körper in Kontakt kommen (z. B. In vitro-Diagnostika);
biologische Risiken infolge von physikalischen Wechselwirkungen mit dem Körper (d. h. durch Anwendung von mechanischen Kräften, von Energie oder aufgrund der Oberflächenmorphologie usw.), sofern die chemische Exposition unverändert ist;
arzneilich wirksame Bestandteile von Produkt-Arzneimittel-Kombinationen oder biologische Komponen¬ten von Produkt-Biologikum-Kombinationen, da hier zusätzliche rechtliche Erwägungen gelten können;
die Exposition gegenüber einem bestimmten Bestandteil, der aus anderen Quellen als dem Produkt stammt, z. B. aus der Nahrung, dem Wasser oder der Luft.
Évaluation biologique des dispositifs médicaux - Partie 17: Appréciation du risque toxicologique des constituants des dispositifs médicaux (ISO 10993-17:2023)
Le présent document spécifie le processus et les exigences pour l'appréciation du risque toxicologique des constituants des dispositifs médicaux. Les méthodes et les critères utilisés pour évaluer si l'exposition à un constituant ne présente pas de dommages significatifs sont également spécifiés. L'appréciation du risque toxicologique peut faire partie de l'évaluation biologique du produit final, comme décrit dans l'ISO 10993-1.
Le processus décrit dans le présent document s'applique aux informations relatives à la caractérisation chimique collectées conformément à l'ISO 10993-18. Lorsqu'une appréciation du risque toxicologique portant sur les informations relatives à la composition ou sur les données de chimie analytique (par exemple, données sur les extractibles ou sur les relargables) est nécessaire pour déterminer si les risques toxicologiques liés aux constituants sont négligeables ou tolérables.
Le processus décrit dans le présent document n'est pas destiné à s'appliquer aux cas où le risque toxicologique a été estimé par d'autres moyens, par exemple:
— les constituants, à l'exclusion de la cohorte préoccupante ou des produits chimiques exclus, qui sont présents ou extraits d'un dispositif médical à une quantité représentative de l'exposition du patient inférieure à un seuil de déclaration pertinent, fondé sur des critères toxicologiques (voir les exigences applicables de l'ISO 10993-18:2020, l'Annexe E et l'ISO/TS 21726);
— un dispositif médical nouveau ou modifié pour lequel une équivalence chimique ou biologique a été établie avec un dispositif médical existant biocompatible ou cliniquement établi (voir les exigences applicables de l'ISO 10993-18:2020, Annexe C).
Par ailleurs, le processus décrit dans le présent document ne s'applique pas:
— aux constituants des dispositifs médicaux qui n'entrent pas en contact avec le corps (par exemple, les dispositifs de diagnostic in vitro);
— aux risques biologiques associés aux interactions physiques du dispositif médical avec le corps (c'est-à-dire l'application de forces mécaniques, d'énergie ou de la morphologie de la surface, etc.), à condition que l'exposition chimique reste inchangée;
— aux ingrédients pharmaceutiques actifs des produits combinés dispositif/médicament ou aux composants biologiques des produits combinés dispositif/substance biologique, selon les considérations réglementaires supplémentaires qui peuvent s'appliquer;
— à l'exposition à un constituant particulier provenant d'autres sources que le dispositif, comme la nourriture, l'eau et l'air.
Biološko ovrednotenje medicinskih pripomočkov - 17. del: Toksikološka ocena tveganja glede sestavin medicinskih pripomočkov (ISO 10993-17:2023)
Ta dokument določa postopek in zahteve za toksikološko oceno tveganja glede sestavin medicinskih pripomočkov. Metode in kriteriji za ocenjevanje, ali je izpostavljenost sestavini brez znatnega škodljivega učinka, so prav tako navedeni. Toksikološka ocena tveganja je lahko del biološkega ovrednotenja končnega proizvoda, kot je opisano v standardu ISO 10993-1.
Postopek, opisan v tem dokumentu, velja za informacije o kemijski karakterizaciji, pridobljene v skladu s standardom ISO 10993-18. Če so potrebne toksikološke ocene tveganja informacij o sestavi ali analitičnih kemijskih podatkov (npr. podatkov, ki jih je mogoče pridobiti ali izločiti) za določanje toksikoloških tveganj v zvezi s sestavinami zanemarljive ali dopustne.
Postopek, opisan v tem dokumentu, ni namenjen za uporabo v okoliščinah, ko je toksikološko tveganje ocenjeno z drugimi sredstvi, npr.:
– iz sestavin, brez sklopa dvomljivih ali izločenih kemikalij, ki so prisotne v ali ekstrahirane iz medicinskega pripomočka v količini, ki predstavlja izpostavljenost pacienta, ki je nižja od pomembnega, toksikološko osnovanega pragu za poročanje (glej veljavne zahteve v standardu ISO 10993-18:2020, dodatek E in standard ISO/TS 21726);
– z novim ali spremenjenim medicinskim pripomočkom, za katerega je ugotovljena kemijska ali biološka enakovrednost z obstoječim biološko združljivim ali klinično uveljavljenim medicinskim pripomočkom (glej veljavne zahteve v standardu ISO 10993-18:2020, dodatek C).
Postopek, opisan v tem dokumentu, se prav tako ne uporablja za:
– sestavine medicinskih pripomočkov, ki ne pridejo v stik s telesom (npr. diagnostika in vitro);
– biološka tveganja, povezana s fizičnimi interakcijami med medicinskim pripomočkom in telesom (tj. uporaba mehanskih sil energije ali površine itd.) pod pogojem, da se kemijska izpostavljenost ni spremenila;
– aktivne farmacevtske sestavine izdelkov s kombinacijo pripomoček-zdravilo ali biološke sestavine izdelkov s kombinacijo pripomoček-biološka sestavina, saj v teh primerih lahko veljajo dodatne zakonske zahteve;
– izpostavljenost določeni sestavini, ki ne izvira iz pripomočka, npr. živila, voda ali zrak.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
01-marec-2024
Biološko ovrednotenje medicinskih pripomočkov - 17. del: Toksikološka ocena
tveganja glede sestavin medicinskih pripomočkov (ISO 10993-17:2023)
Biological evaluation of medical devices - Part 17: Toxicological risk assessment of
medical device constituents (ISO 10993-17:2023)
Biologische Beurteilung von Medizinprodukten - Teil 17: Toxikologische Risikobewertung
von Medizinproduktbestandteilen (ISO 10993-17:2023)
Évaluation biologique des dispositifs médicaux - Partie 17: Appréciation du risque
toxicologique des constituants des dispositifs médicaux (ISO 10993-17:2023)
Ta slovenski standard je istoveten z: EN ISO 10993-17:2023
ICS:
11.100.20 Biološko ovrednotenje Biological evaluation of
medicinskih pripomočkov medical devices
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
EN ISO 10993-17
EUROPEAN STANDARD
NORME EUROPÉENNE
November 2023
EUROPÄISCHE NORM
ICS 11.100.20 Supersedes EN ISO 10993-17:2009
English Version
Biological evaluation of medical devices - Part 17:
Toxicological risk assessment of medical device
constituents (ISO 10993-17:2023)
Évaluation biologique des dispositifs médicaux - Partie Biologische Beurteilung von Medizinprodukten - Teil
17: Appréciation du risque toxicologique des 17: Toxikologische Risikobewertung von
constituants des dispositifs médicaux (ISO 10993- Medizinproduktbestandteilen (ISO 10993-17:2023)
17:2023)
This European Standard was approved by CEN on 2 July 2023.
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, Türkiye 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
© 2023 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 10993-17:2023 E
worldwide for CEN national Members.
Contents Page
European foreword . 3
Annex ZA (informative) Relationship between this European Standard and the General
Safety and Performance Requirements of Regulation (EU) 2017/745 aimed to be
covered. 4
European foreword
This document (EN ISO 10993-17:2023) 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 May 2024, and conflicting national standards shall be
withdrawn at the latest by May 2024.
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 10993-17:2009.
This document has been prepared under a Standardization Request given to CEN by the European
Commission and the European Free Trade Association, and supports essential requirements of EU
Directive(s) / Regulation(s).
For the relationship with EU Directive(s) / Regulation(s), see informative Annex ZA, which is an integral
part of this document.
Any feedback and questions on this document should be directed to the users’ national standards
body/national committee. A complete listing of these bodies can be found on the CEN website.
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, Türkiye and the
United Kingdom.
Endorsement notice
The text of ISO 10993-17:2023 has been approved by CEN as EN ISO 10993-17:2023 without any
modification.
Annex ZA
(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 M/575 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] and to system or process requirements including
those relating to quality management systems, risk management, post-market surveillance systems,
clinical investigations, clinical evaluation or post-market clinical follow-up.
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 and application of the
edition of the normatively referenced standards as given in Table ZA.2 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.
Where a definition in this harmonised standard differs from a definition of the same term set out in
Regulation (EU) 2017/745, the differences shall be indicated in the Annex Z. For the purpose of using
this standard in support of the requirements set out in Regulation (EU) 2017/745, the definitions set
out in this Regulation prevail.
Where the European standard is an adoption of an International Standard, the scope of this document
can differ from the scope of the European Regulation that it supports. As the scope of the applicable
regulatory requirements differ from nation to nation and region to region the standard can only
support European regulatory requirements to the extent of the scope of the European Regulation for
medical devices ((EU) 2017/745).
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 When a General Safety and Performance Requirement does not appear in Table ZA.1, it means that it is
not addressed by this European Standard.
Table ZA.1 — Correspondence between this European Standard and Annex I
of Regulation (EU) 2017/745 [OJ L 117] and to system or process requirements including those
relating to quality management systems, risk management, post-market surveillance systems, clinical
investigations, clinical evaluation or post-market clinical follow-up
General Safety and
Clause(s)/subclause(s)
Performance Requirements
of Remarks/Notes
of Regulation
this EN
(EU) 2017/745
EN ISO 10993-17 addresses the choice of
materials as regards toxicity, but 10.1 is
only partly covered. Flammability and
mechanical or physical (e.g., surface)
properties are not covered. This standard
provides requirements for a toxicological
risk assessment process for constituents
present in or on, or released from, a
medical device.
This risk assessment process involves the
identification of substances that have the
capacity to interact with biological
tissues, cells or body fluids and the
assessment of the nature and likelihood
of any associated harm to health arising
as a result of the intended use of the
medical device. While such an assessment
can confirm the absence of appreciable
toxicological risk, it does not necessarily
5, 6, 7, 8, 9, 10 and Annex
demonstrate the ability of a medical
10.1 a), b), d), e), and h) A, Annex B, Annex C and
device or material to perform with an
Annex E
appropriate host response in a specific
application.
The toxicological risk assessment is based
on the composition of the finished
medical device, which is dependent, in
part, on the processing materials used
and the impact of processes on the
materials of manufacture.
Where appropriate and necessary for the
risk assessment, quantitative structure-
activity relationships or mathematical
models can be used as part of the process
specified.
The standard provides requirements for a
process for specifying a level of exposure
to a constituent of a medical device that
is without appreciable harm to health
and for confirming that a medical device
meets the specification so defined.
EN ISO 10993-17 addresses risks posed by
contaminants and residues. However,
10.2 is only partly covered by this
standard, since the standard does not
provide requirements for design,
manufacture and packaging. Although
this standard does not oblige
manufacturers to minimize the risk posed
by contaminants and residues in medical
devices, it provides a means to estimate
5, 6, 7, 8, 9, 10 and Annex
those risks and demonstrate that they
10.2 A, Annex B, Annex C and
have been minimized.
Annex E
The primary focus of this standard is the
risk to patients, but risks to users coming
into contact with a medical device are
also addressed. However the standard is
not applicable to medical device
constituents that do not contact the body,
so risks to persons involved in the
transport or storage of medical devices
would not normally be addressed.
EN ISO 10993-17 addresses risks posed by
substances, including degradation
products and processing residues.
However, 10.4.1 is only partly covered by
this standard, since the standard does not
provide requirements for design and
manufacture, nor does it address risks
associated with particles, including wear
debris, from medical devices. Although
this standard does not oblige
manufacturers to minimize the
toxicological risk posed by substances in
medical devices, it provides a means to
estimate those risks and demonstrate
5, 6, 7, 8, 9, 10 and Annex
that they have been minimized.
10.4.1 A, Annex B, Annex C and
Annex E
The process specified by this standard
includes the identification of substances
which are carcinogenic, mutagenic or
toxic to reproduction or that have
endocrine-disrupting properties. Where
such substances are identified, it provides
a means for estimation of potential
patient or user exposure to the substance
that can form a basis for a justification
regarding the presence of the substance
and for appropriate labelling. However
the standard does not include
acceptability criteria or labelling
requirements.
Table ZA.2 — Applicable Standards to confer presumption of conformity as described in this
Annex ZA
Column 1 Column 2 Column 3 Column 4
Reference in International
Title Corresponding European
Clause 2 Standard Edition
Standard Edition
ISO ISO 10993-1:2018 Biological evaluation of medical EN ISO 10993-1:2020
10993-1:2018 devices — Part 1: Evaluation and
testing within a risk management
process
ISO ISO 10993-18:2020 Biological evaluation of medical EN ISO 10993-18:2020
10993-18:2020 devices — Part 18: Chemical
characterization of medical device
materials within a risk
management process
ISO/TS ISO/TS Biological evaluation of medical For applicable standard
21726:2019 21726:2019 devices — Application of the edition see Column 2
threshold of toxicological concern
(TTC) for assessing
biocompatibility of medical device
constituents
ISO 14971:2019 ISO 14971:2019 Medical devices — Application of EN ISO 14971:2019
risk management to medical
EN ISO
devices
14971:2019/A11:2021
The documents listed in the Column 1 of table ZA.2, in whole or in part, are normatively referenced in
this document, i.e. are indispensable for its application. The achievement of the presumption of
conformity is subject to the application of the edition of Standards as listed in Column 4 or, if no
European Standard Edition exists, the International Standard Edition given in Column 2 of table ZA.2.
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 c
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