EN ISO 10993-1:2020
(Main)Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process (ISO 10993-1:2018, including corrected version 2018-10)
Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process (ISO 10993-1:2018, including corrected version 2018-10)
This document specifies:
— the general principles governing the biological evaluation of medical devices within a risk management process;
— the general categorization of medical devices based on the nature and duration of their contact with the body;
— the evaluation of existing relevant data from all sources;
— the identification of gaps in the available data set on the basis of a risk analysis;
— the identification of additional data sets necessary to analyse the biological safety of the medical device;
— the assessment of the biological safety of the medical device.
This document applies to evaluation of materials and medical devices that are expected to have direct or indirect contact with:
— the patient's body during intended use;
— the user's body, if the medical device is intended for protection (e.g., surgical gloves, masks and others).
This document is applicable to biological evaluation of all types of medical devices including active, non-active, implantable and non-implantable medical devices.
This document also gives guidelines for the assessment of biological hazards arising from:
— risks, such as changes to the medical device over time, as a part of the overall biological safety assessment;
— breakage of a medical device or medical device component which exposes body tissue to new or novel materials.
Other parts of ISO 10993 cover specific aspects of biological assessments and related tests. Device-specific or product standards address mechanical testing.
This document excludes hazards related to bacteria, moulds, yeasts, viruses, transmissible spongiform encephalopathy (TSE) agents and other pathogens.
Biologische Beurteilung von Medizinprodukten - Teil 1: Beurteilung und Prüfungen im Rahmen eines Risikomanagementsystems (ISO 10993-1:2018, einschließlich korrigierte Fassung 2018-10)
Dieses Dokument legt das Folgende fest:
- die allgemeinen Grundsätze, die für die biologische Beurteilung von Medizinprodukten innerhalb eines Risikomanagementverfahrens gelten;
- die allgemeine Einteilung von Medizinprodukten, basierend auf der Art und Dauer von deren Kontakt mit dem Körper;
- die Auswertung vorhandener relevanter Daten aus allen Quellen;
- die Ermittlung von Lücken in den verfügbaren Datensätzen auf der Grundlage einer Risikoanalyse;
- die Ermittlung zusätzlicher Datensätze, die für die Analyse der biologischen Sicherheit des Medizin¬produkts notwendig sind;
- die Beurteilung der biologischen Sicherheit des Medizinprodukts.
Dieses Dokument gilt für die Beurteilung von Materialien und Medizinprodukten, von denen erwartet wird, dass sie direkt oder indirekt in Kontakt kommen mit
- dem Körper des Patienten im Rahmen der bestimmungsgemäßen Verwendung, und/oder
- dem Körper des Anwenders, wenn das Medizinprodukt zum Schutz vorgesehen ist (z. B. OP-Hand-schuhe, Masken und andere Produkte).
Dieses Dokument ist anwendbar auf die biologische Beurteilung aller Arten an Medizinprodukten, einschließlich aktiver, nicht aktiver, implantierbarer und nicht implantierbarer Medizinprodukte.
Dieses Dokument bietet außerdem einen Leitfaden zur Beurteilung von biologischen Gefährdungen aufgrund von
- Risiken, wie etwa Veränderungen des Medizinprodukts im Laufe der Zeit, als Teil der biologischen Sicherheitsbewertung, und/oder
- Beschädigung eines Medizinprodukts oder eines Bestandteils des Medizinprodukts, was zur Folge hat, dass Körpergewebe neuen oder neu entstandenen Materialien ausgesetzt wird.
Andere Teile der ISO 10993 decken spezifische Aspekte der biologischen Beurteilungen und zugehörigen Prüfungen ab. Spezifische Normen für das Medizinprodukt oder Produktnormen behandeln die mechanische Prüfung.
Gefährdungen im Zusammenhang mit Bakterien, Schimmelpilzen, Hefen, Viren, den Erregern der Trans¬missiblen Spongiformen Enzephalopathie (TSE) und weiteren pathogenen Organismen werden in diesem Dokument nicht behandelt.
Évaluation biologique des dispositifs médicaux - Partie 1: Évaluation et essais au sein d'un processus de gestion du risque (ISO 10993-1:2018, y compris version corrigée 2018-10)
Le présent document spécifie:
— les principes généraux sur lesquels repose l'évaluation biologique des dispositifs médicaux dans un processus de gestion du risque;
— la classification générale des dispositifs médicaux, fondée sur la nature et la durée de leur contact avec le corps humain;
— l'évaluation de toutes les données pertinentes existantes;
— l'identification de lacunes dans les ensembles de données disponibles sur la base d'une analyse de risque;
— l'identification d'ensembles de données supplémentaires nécessaires à l'analyse de la sécurité biologique du dispositif médical;
— l'évaluation de la sécurité biologique du dispositif médical.
Le présent document s'applique à l'évaluation de matériaux et dispositifs médicaux qui sont destinés à entrer en contact direct ou indirect avec:
— le corps du patient pendant leur utilisation prévue;
— le corps de l'utilisateur si le dispositif médical est destiné à la protection (par exemple gants chirurgicaux, masques et autres).
Le présent document est applicable à l'évaluation biologique de tous types de dispositifs médicaux, y compris les dispositifs médicaux actifs, non actifs, implantables et non implantables.
Le présent document donne également des lignes directrices pour l'évaluation des dangers biologiques provenant de:
— risques tels que des modifications du dispositif médical au fil du temps, dans le cadre de l'évaluation de sécurité biologique générale;
— rupture d'un dispositif médical ou d'un composant de dispositif médical qui expose des tissus de l'organisme à des matériaux nouveaux.
Les autres parties de l'ISO 10993 couvrent des aspects spécifiques des évaluations biologiques et des essais associés. Des normes de produits ou spécifiques aux dispositifs traitent des essais mécaniques.
Le présent document exclut les dangers relatifs aux bactéries, moisissures, levures, virus, agents de l'encéphalopathie spongiforme transmissible (EST) et autres agents pathogènes.
Biološko ovrednotenje medicinskih pripomočkov - 1. del: Ocena in preskušanje znotraj procesa obvladovanja tveganja (ISO 10993-1:2018, vključno s popravkom verzije 2018-11)
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
01-februar-2021
Nadomešča:
SIST EN ISO 10993-1:2010
SIST EN ISO 10993-1:2010/AC:2010
Biološko ovrednotenje medicinskih pripomočkov - 1. del: Ocena in preskušanje
znotraj procesa obvladovanja tveganja (ISO 10993-1:2018, vključno s popravkom
verzije 2018-11)
Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk
management process (ISO 10993-1:2018, including corrected version 2018-11)
Biologische Beurteilung von Medizinprodukten - Teil 1: Beurteilung und Prüfungen im
Rahmen eines Risikomanagementsystems (ISO 10993-1:2018, einschließlich korrigierte
Fassung 2018-11)
Évaluation biologique des dispositifs médicaux - Partie 1: Évaluation et essais au sein
d'un processus de gestion du risque (ISO 10993-1:2018, y compris version corrigée
2018-11)
Ta slovenski standard je istoveten z: EN ISO 10993-1:2020
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 10993-1
EUROPEAN STANDARD
NORME EUROPÉENNE
December 2020
EUROPÄISCHE NORM
ICS 11.100.20 Supersedes EN ISO 10993-1:2009
English Version
Biological evaluation of medical devices - Part 1:
Evaluation and testing within a risk management process
(ISO 10993-1:2018, including corrected version 2018-11)
Évaluation biologique des dispositifs médicaux - Partie Biologische Beurteilung von Medizinprodukten - Teil 1:
1: Évaluation et essais au sein d'un processus de Beurteilung und Prüfungen im Rahmen eines
gestion du risque (ISO 10993-1:2018, y compris Risikomanagementsystems (ISO 10993-1:2018,
version corrigée 2018-11) einschließlich korrigierte Fassung 2018-11)
This European Standard was approved by CEN on 10 December 2020.
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 10993-1:2020 E
worldwide for CEN national Members.
Contents Page
European foreword . 3
European foreword
This document (EN ISO 10993-1:2020) 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 June 2021, and conflicting national standards shall be
withdrawn at the latest by June 2021.
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 10993-1:2009.
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 10993-1:2018, including corrected version 2018-11 has been approved by CEN as
INTERNATIONAL ISO
STANDARD 10993-1
Fifth edition
2018-08
Corrected version
2018-10
Biological evaluation of medical
devices —
Part 1:
Evaluation and testing within a risk
management process
Évaluation biologique des dispositifs médicaux —
Partie 1: Évaluation et essais au sein d'un processus de gestion du
risque
Reference number
ISO 10993-1:2018(E)
©
ISO 2018
ISO 10993-1:2018(E)
© 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: +41 22 749 01 11
Fax: +41 22 749 09 47
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2018 – All rights reserved
ISO 10993-1:2018(E)
Contents Page
Foreword .iv
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 General principles applying to biological evaluation of medical devices .5
5 Categorization of medical devices . 9
5.1 General . 9
5.2 Categorization by nature of body contact . 9
5.2.1 Non-contacting medical devices. 9
5.2.2 Surface-contacting medical devices .10
5.2.3 Externally communicating medical devices .10
5.2.4 Implant medical devices .11
5.3 Categorization by duration of contact .11
5.3.1 Contact duration categories .11
5.3.2 Transitory-contacting medical devices .11
5.3.3 Medical devices with multiple contact duration categories .11
6 Biological evaluation process .12
6.1 Physical and chemical information for biological risk analysis .12
6.2 Gap analysis and selection of biological endpoints for assessment .12
6.3 Biological testing .13
6.3.1 General.13
6.3.2 Testing for evaluation .14
7 Interpretation of biological evaluation data and overall biological risk assessment .18
Annex A (informative) Endpoints to be addressed in a biological risk assessment.20
Annex B (informative) Guidance on the conduct of biological evaluation within a risk
management process .25
Annex C (informative) Suggested procedure for literature review .38
Bibliography .40
ISO 10993-1:2018(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 fifth edition cancels and replaces the fourth edition (ISO 10993-1:2009), which has been technically
revised. It also incorporates the Technical Corrigendum ISO 10993-1:2009/Cor.1:2010.
The main changes compared to the previous edition are as follows:
a) revised Annex A “Endpoints to be addressed in a biological risk assessment” with new columns for
“physical and/or chemical information” and “material mediated pyrogenicity” as well as columns
for “chronic toxicity,” “carcinogenicity,” “reproductive/developmental toxicity,” and “degradation”
which now indicates “endpoints” to be considered with “E” (instead of “tests” to be conducted with
an “X”);
b) replaced Annex B “Guidance on the risk management process” with “Guidance on the conduct of
biological evaluation within a risk management process” (formerly ISO TR 15499);
c) additional definitions for terms used throughout the ISO 10993 series of standards;
d) additional information on the evaluation of “Non-contacting medical devices” and new information
on the evaluation of “Transitory-contacting medical devices”;
e) additional information on the evaluation of nanomaterials, and absorbable materials;
f) additional reference to ISO 18562 (all parts) for “Biocompatibility evaluation of breathing gas
pathways in healthcare applications”;
g) significant editing changes throughout the document;
A list of all parts in the ISO 10993 series can be found on the ISO website.
This corrected version of ISO 10993-1:2018 incorporates the following correction.
iv © ISO 2018 – All rights reserved
ISO 10993-1:2018(E)
th
—In Table A.1, 6 column, “Sensitization” has been added as a table heading.
ISO 10993-1:2018(E)
Introduction
The primary aim of this document is the protection of humans from potential biological risks arising
from the use of medical devices. It is compiled from numerous International and national standards
and guidelines concerning the biological evaluation of medical devices. It is intended to describe the
biological evaluation of medical devices within a risk management process, as part of the overall
evaluation and development of each medical device. This approach combines the review and evaluation
of existing data from all sources with, where necessary, the selection and application of additional tests,
thus enabling a full evaluation to be made of the biological responses to each medical device, relevant
to its safety in use. The term “medical device” is wide-ranging and, at one extreme, consists of a single
material, which can exist in more than one physical form, and at the other extreme, of a medical device
consisting of numerous components made of more than one material.
This document addresses the determination of the biological response to medical devices, mostly in a
general way, rather than in a specific device-type situation. Thus, for a complete biological evaluation, it
classifies medical devices according to the nature and duration of their anticipated contact with human
tissues when in use and indicates, in a matrix, the biological endpoints that are thought to be relevant in
the consideration of each medical device category. See also 3.14, Note 1 to entry.
The range of biological hazards is wide and complex. The biological response to a constituent material
alone cannot be considered in isolation from the overall medical device design. Thus, in designing a
medical device, the choice of the best material with respect to its biocompatibility might result in a
less functional medical device, biocompatibility being only one of a number of characteristics to be
considered in making that choice. Where a material is intended to interact with tissue in order to
perform its function, the biological evaluation needs to address this.
Biological responses that are regarded as adverse, caused by a material in one application, might not be
regarded as such in a different situation. Biological testing is based upon, among other things, in vitro
and ex vivo test methods and upon animal models, so that the anticipated behaviour when a medical
device is used in humans can be judged only with caution, as it cannot be unequivocally concluded
that the same biological response will also occur in this species. In addition, differences in the manner
of response to the same material among individuals indicate that some patients can have adverse
reactions, even to well-established materials.
The primary role of this document is to serve as a framework in which to plan a biological evaluation. A
secondary role is to utilize scientific advances in our understanding of basic mechanisms, to minimize
the number and exposure of test animals by giving preference to in vitro models and to chemical,
physical, morphological, and topographical characterization testing, in situations where these methods
yield equally relevant information to that obtained from in vivo models.
It is not intended that this document provide a rigid set of test methods, including pass/fail criteria,
as this might result in either an unnecessary constraint on the development and use of novel medical
devices, or a false sense of security in the general use of medical devices. Where a particular application
warrants it, experts in the product or in the area of application concerned can choose to establish
specific tests and criteria, described in a product-specific vertical standard.
ISO 10993 series is intended for use by professionals, appropriately qualified by training and experience,
who are able to interpret its requirements and judge the outcome of the evaluation for each medical
device, taking into consideration all the factors relevant to the medical device, its intended use and the
current knowledge of the medical device provided by review of the scientific literature and previous
clinical experience.
Informative Annex A contains a table that is generally helpful in identifying endpoints recommended
in the biocompatibility evaluation of medical devices, according to their category of body contact and
duration of clinical exposure. Informative Annex B contains guidance for the application of the risk
management process to medical devices which encompasses biological evaluation.
vi © ISO 2018 – All rights reserved
INTERNATIONAL STANDARD ISO 10993-1:2018(E)
Biological evaluation of medical devices —
Part 1:
Evaluation and testing within a risk management process
1 Scope
This document specifies:
— the general principles governing the biological evaluation of medical devices within a risk
management process;
— the general categorization of medical devices based on the nature and duration of their contact with
the body;
— the evaluation of existing relevant data from all sources;
— the identification of gaps in the available data set on the basis of a risk analysis;
— the identification of additional data sets necessary to analyse the biological safety of the medical
device;
— the assessment of the biological safety of the medical device.
This document applies to evaluation of materials and medical devices that are expected to have direct
or indirect contact with:
— the patient's body during intended use;
— the user’s body, if the medical device is intended for protection (e.g., surgical gloves, masks and
others).
This document is applicable to biological evaluation of all types of medical devices including active,
non-active, implantable and non-implantable medical devices.
This document also gives guidelines for the assessment of biological hazards arising from:
— risks, such as changes to the medical device over time, as a part of the overall biological safety
assessment;
— breakage of a medical device or medical device component which exposes body tissue to new or
novel materials.
Other parts of ISO 10993 cover specific aspects of biological assessments and related tests. Device-
specific or product standards address mechanical testing.
This document excludes hazards related to bacteria, moulds, yeasts, viruses, transmissible spongiform
encephalopathy (TSE) agents and other pathogens.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements of this document. For dated references, only the edition cited applies. For
undated references, the latest edition of the referenced document (including any amendments) applies.
ISO 10993-2:2006, Biological evaluation of medical devices — Part 2: Animal welfare requirements
ISO 10993-1:2018(E)
ISO 10993-3, Biological evaluation of medical devices — Part 3: Tests for genotoxicity, carcinogenicity and
reproductive toxicity
ISO 10993-4, Biological evaluation of medical devices — Part 4: Selection of tests for interactions with blood
ISO 10993-5, Biological evaluation of medical devices — Part 5: Tests for in vitro cytotoxicity
ISO 10993-6, Biological evaluation of medical devices — Part 6: Tests for local effects after implantation
ISO 10993-7, Biological evaluation of medical devices — Part 7: Ethylene oxide sterilization residuals
ISO 10993-9, Biological evaluation of medical devices — Part 9: Framework for identification and
quantification of potential degradation products
ISO 10993-10, Biological evaluation of medical devices — Part 10: Tests for irritation and skin sensitization
ISO 10993-11:2017, Biological evaluation of medical devices — Part 11: Tests for systemic toxicity
ISO 10993-12, Biological evaluation of medical devices — Part 12: Sample preparation and reference
materials
ISO 10993-13, Biological evaluation of medical devices — Part 13: Identification and quantification of
degradation products from polymeric medical devices
ISO 10993-14, Biological evaluation of medical devices — Part 14: Identification and quantification of
degradation products from ceramics
ISO 10993-15, Biological evaluation of medical devices — Part 15: Identification and quantification of
degradation products from metals and alloys
ISO 10993-16, Biological evaluation of medical devices — Part 16: Toxicokinetic study design for
degradation products and leachables
ISO 10993-17, Biological evaluation of medical devices — Part 17: Establishment of allowable limits for
leachable substances
ISO 10993-18, Biological evaluation of medical devices — Part 18: Chemical characterization of materials
ISO/TS 10993-20, Biological evaluation of medical devices — Part 20: Principles and methods for
immunotoxicology testing of medical devices
ISO 14971:2007, Medical devices — Application of risk management to medical devices
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— IEC Electropedia: available at http: //www .electropedia .org/
— ISO Online browsing platform: available at https: //www .iso .org/obp
3.1
biocompatibility
ability of a medical device (3.14) or material (3.12) to perform with an appropriate host response in a
specific application
3.2
biological risk
combination of the probability of harm to health occurring as a result of adverse reactions associated
with medical device (3.14) or material (3.12) interactions, and the severity of that harm
2 © ISO 2018 – All rights reserved
ISO 10993-1:2018(E)
3.3
biological safety
freedom from unacceptable biological risk (3.2) in the context of the intended use
3.4
chemical constituent
any synthetic or natural substance that is used in a process for manufacturing materials (3.12) and/
or medical devices (3.14), including the base material(s), additives (antioxidants, UV stabilizers, color
additives, dyes, etc.), and processing aids (solvents, lubricants, antifoaming agents, etc.)
3.5
data set
information, such as physical and/or chemical characterization, toxicity data, etc. from a variety of
sources necessary to characterize the biological response to a medical device
3.6
direct contact
medical device (3.14) or medical device component that comes into physical contact with body tissue
3.7
externally communicating medical device
medical device (3.14) or medical device component that is partially or wholly located outside the body
but has either direct or indirect contact with the internal body fluids and/or tissues
3.8
final product
medical device (3.14) or medical device component that has been subjected to all manufacturing
processes for the “to be marketed” medical device including packaging and if applicable, sterilization
3.9
geometry
device configuration
shape and relative arrangement of the parts of the medical device (3.14)
3.10
implant
medical device (3.14) which is intended to be totally introduced into the human body or to replace an
epithelial surface or the surface of the eye by means of clinical intervention and which is intended to
remain in place after the procedure
3.11
indirect contact
medical device (3.14) or medical device component through which a fluid or gas passes, prior to the fluid
or gas coming into physical contact with body tissue (in this case the medical device or medical device
component itself does not physically contact body tissue)
3.12
material
synthetic or natural polymer, metal or alloy, ceramic, or composite, including tissue rendered non-
viable, used as a medical device (3.14) or any part thereof
3.13
material characterization
broad and general process of collecting existing information about a material’s chemistry, structure
and other properties, and if appropriate, new data, to facilitate the evaluation of these properties
3.14
medical device
any instrument, apparatus, implement, machine, appliance, implant, reagent for in vitro use, software,
material (3.12) or other similar or related article, intended by the manufacturer to be used, alone or in
combination, for human beings, for one or more of the specific medical purpose(s) of:
ISO 10993-1:2018(E)
— diagnosis, prevention, monitoring, treatment or alleviation of disease;
— diagnosis, monitoring, treatment, alleviation of or compensation for an injury;
— investigation, replacement, modification, or support of the anatomy or of a physiological process;
— supporting or sustaining life;
— control of conception;
— disinfection of medical devices;
— providing information by means of in vitro examination of specimens derived from the human body;
and does not achieve its primary intended action by pharmacological, immunological or metabolic
means, in or on the human body, but which may be assisted in its intended function by such means.
Medical devices include dental devices.
Note 1 to entry: Products which may be considered to be medical devices in some jurisdictions but not in others
include:
— disinfection substances;
— aids for persons with disabilities;
— devices incorporating animal and/or human tissues;
— devices for in vitro fertilization or assisted reproduction technologies;
[SOURCE: GHTF/SG1/N071: 2012, 5.1 modified to clarify that dental devices are included]
3.15
nanomaterial
material (3.12) with any external dimension in the nanoscale or having internal structure or surface
structure in the nanoscale
[SOURCE: ISO/TR 10993-22:2017, 3. 7, modified — Notes to entry have been deleted.]
3.16
non-contacting
indicates that the medical device (3.14) or medical device component has neither direct nor indirect
contact with body tissues
3.17
physical and chemical information
knowledge regarding formulation, manufacturing processes, geometric and physical properties and
type of body contact and clinical use that is used to determine whether any additional biological or
material characterization testing is needed
3.18
risk analysis
systematic use of available information to identify hazards and to estimate the risk
[SOURCE: ISO 14971:2007, 2.17, modified— The Note has been deleted.]
3.19
risk assessment
overall process comprising a risk analysis (3.18) and a risk evaluation (3.20)
[SOURCE: ISO 14971:2007, 2.18]
4 © ISO 2018 – All rights reserved
ISO 10993-1:2018(E)
3.20
risk evaluation
process of comparing the estimated risk against given risk criteria to determine the acceptability of
the risk
[SOURCE: ISO 14971:2007, 2.21]
3.21
risk management
systematic application of management policies, procedures and practices to the tasks of analysing,
evaluating, controlling and monitoring risk
[SOURCE: ISO 14971:2007, 2.22]
3.22
toxic
capable of causing an adverse biological response
3.23
toxicological hazard
potential for a chemical substance or material (3.12) to cause an adverse biological reaction, taking into
account the nature of the reaction and the dose required to elicit it
3.24
toxicological risk
probability of a specified degree of an adverse reaction occurring in response to a specified level of
exposure
3.25
toxicological threshold
limit, such as a tolerable intake (TI), tolerable exposure (TE), allowable limit (AL) value, or Threshold
of Toxicological Concern (TTC) below which adverse effects are not expected for relevant biological
endpoints
3.26
transitory contact
medical device (3.14) or medical device component that has a very brief duration of contact with
body tissue
4 General principles applying to biological evaluation of medical devices
4.1 The biological evaluation of any material or medical device intended for use in humans shall form
part of a structured biological evaluation plan within a risk management process in accordance with
ISO 14971:2007, Annex I, as given in Figure 1 of this document. This risk management process involves
identification of biological hazards, estimation of the associated biological risks, and determination of
their acceptability. Annex B provides guidance on this process. The biological evaluation shall be planned,
carried out, and documented by knowledgeable and experienced professionals.
The risk management plan should identify aspects of the biological evaluation requiring specific
technical competencies and shall identify the person(s) responsible for the biological evaluation.
The evaluation shall include documented, informed consideration of advantages/disadvantages and
relevance of:
a) medical device configuration (e.g. size, geometry, surface properties) and a listing of a medical
device’s materials of construction (qualitative) and where necessary, the proportion and amount
(mass) of each material in the medical device (quantitative);
b) the physical and chemical characteristics of the various materials of construction and their
composition;
ISO 10993-1:2018(E)
NOTE Where this information is already documented within the risk management for the medical
device, it can be included by reference.
c) any history of clinical use or human exposure data;
NOTE Previous regulatory approval history can be relevant.
d) any existing toxicology and other biological safety data on product and component materials,
breakdown products and metabolites;
e) test procedures.
Evaluation can include both a review of relevant existing preclinical and clinical data and actual
testing. Such an evaluation might result in the conclusion that no testing is needed if the material has
a demonstrable safe history of use in a specified role and physical form that is equivalent to that of the
medical device under design. The type of information that can be useful to demonstrate equivalence is
included in Annex B. Testing is usually not necessary when sufficient information is already available to
perform a risk assessment of the material and/or the medical device (see Annex C).
4.2 In the selection of materials to be used in the medical device manufacture, the first consideration
shall be fitness for purpose with regard to characteristics and properties of the material, which include
chemical, toxicological, physical, electrical, morphological and mechanical properties.
4.3 The following shall be taken into account for their relevance to the overall biological evaluation of
the medical device:
a) the material(s) of construction (i.e. all direct and indirect tissue contacting materials);
b) intended additives, process contaminants and residues (for example, testing for ethylene oxide
sterilization residuals shall be conducted in accordance with ISO 10993-7);
c) packaging materials that directly or indirectly contact the medical device can transfer chemicals to
the medical device and then indirectly to the patient or clinician;
d) leachable substances (see ISO 10993-17 and ISO 10993-18);
e) degradation products (see ISO 10993-9, for general principles and 10993-13, 10993-14 and 10993-
15 for degradation products from polymers, ceramics and metals, respectively);
f) other components and their interactions in the final product;
g) the performance and characteristics of the final product;
h) physical characteristics of the final product, including but not limited to, porosity, particle size,
shape and surface morphology.
Description of medical device chemical constituents and consideration of material characterization
including chemical characterization (see ISO 10993-18) shall precede any biological testing (see
Figure 1). Chemical characterization with an appropriate toxicological threshold can be used to
determine if further testing is needed (see Annex B, ISO 10993-17 and ISO 10993-18).
Physical effects of the medical device shall be considered if they impact the biocompatibility.
NOTE See ISO/TR 10993-19 for information.
Medical devices that contain, generate, or are composed of nanomaterials can pose specific challenges
to the biological evaluation due to their potentially unique properties (see ISO/TR 10993-22).
Both local and systemic effects shall be considered for risk evaluation.
4.4 The biological evaluation shall commence with categorization of medical devices (see Clause 6).
Assessment of the information already available then enables a gap analysis to facilitate the selection
6 © ISO 2018 – All rights reserved
ISO 10993-1:2018(E)
of appropriate tests. The rigour necessary in the biological evaluation is principally determined by the
nature, degree, frequency and duration of the exposure and the hazards identified for the medical device
or material. Testing is usually not necessary when sufficient information is already available to perform a
risk assessment of the material and/or the medical device (see Annex C). For example, biological testing is
usually not necessary, if material characterization (e.g. physical and chemical) demonstrates equivalence
to a previously assessed medical device or material with established safety (see ISO 10993-18 and ISO/
TR 10993-19).
The interpretation of the data shall take into account the chemical composition of the materials,
including the conditions of exposure as well as the nature, degree, frequency and duration of exposure
of the body to the medical device or its constituents.
4.5 All known possible biological hazards shall be taken into account for every material and final
product, but this does not imply that testing for all possible hazards will be necessary or practical (see
Clauses 5 and 6). Test results cannot guarantee freedom from potential biological hazards, thus biological
investigations shall be followed by careful observations for unexpected adverse reactions or events in
humans during clinical use of the medical device.
The range of possible biological hazards is wide and can include short-term effects such as acute
toxicity, irritation to the skin, eye and mucosal surfaces, haemolysis and thrombogenicity, as well as
long-term or specific toxic effects such as subchronic and chronic toxic effects, sensitization resulting
in allergy, genotoxicity, carcinogenicity (tumorigenicity) and effects on reproduction or development,
including teratogenicity.
4.6 If testing is needed, selection of any in vitro or in vivo tests (see Annex A) shall be based on
intended use.
In vitro test methods, which are appropriately validated, reasonably and practically available, reliable
and reproducible, shall be considered for use in preference to in vivo tests (see ISO 10993-2). Whenever
in vivo tests are indicated by findings of the initial risk assessment, use of appropriate in vitro screening,
if available, shall be considered before in vivo tests are commenced. A rationale for the testing strategy,
as well as for test selection, shall be provided. Test data, complete to the extent that an independent
analysis could be made, shall be evaluated by competent, informed professionals, and shall be retained.
In certain circumstances, such as for specific medical devices, or biological endpoint assessments, if a
non-standardized, non-validated test is necessary, additional information regarding the rationale for
the study design and data interpretation should be provided.
4.7 The biological safety of a medical device shall be evaluated by the manufacturer over the whole
life-cycle of a medical device.
4.8 For re-usable medical devices, biological safety shall be evaluated for the maximum number of
validated processing cycles by the manufacturer.
ISO 10993-1:2018(E)
Figure 1 — Summary of the systematic approach to a biological evaluation of medical devices as
part of a risk management process
8 © ISO 2018 – All rights reserved
ISO 10993-1:2018(E)
4.9 The biological risk assessment of materials or final products shall be re-evaluated if any of the
following occur:
a) any change in the source or in the specification of the materials used in the manufacture of the
product;
b) any change in the formulation, processing, primary packaging or sterilization of the product;
c) any change in the manufacturer's instructions or expectations concerning storage, e.g. changes in
shelf life and/or transport;
d) any change in the intended use of the product;
e) any evidence that the product can produce adverse biological effects when used in humans.
4.10 The biological evaluation shall take into account preclinical tests, clinical investigations, post-
market experience from similar medical devices or materials, and other relevant information (see
Annex B).
4.11 This document shall not be used to mandate re-testing of historical products assessed previously
using the appropriate edition of this document at the time of the assessment. Nevertheless, compliance
to this new edition shall be shown, by providing a justification for omission of further testing. Where
recommendations for endpoint assessment per Annex A are different from prior published versions
of this document, a history of safe clinical use can be used to document why additional testing on a
commercially-marketed medical device is not needed. However, if any of the changes described in
Clause 4.9 occur, an evaluation of the biologic risks related to the change shall be performed using the
current version of this standard.
5 Categorization of medical devices
5.1 General
Medical devices shall be categorized according to the nature and duration of body contact as specified
in 5.2 and 5.3. The categorization of medical devices facilitates selection of appropriate data sets (see
informative Annex A).
The evaluation of any medical device that does not fall into one of the categories specified shall follow
the general principles contained in this document. Certain medical devices might fall into more than
one body contact or duration category, in which case evaluation appropriate to each category shall be
carried out.
EXAMPLE For medical devices that include both an implanted component, and a delivery system that is used
only during a surgical procedure to place the medical device, the implant should be assessed separately from the
delivery system.
EXAMPLE For gas pathway device components with only indirect contact, device specific standards should
be used to determine the relevant type of biocompatibility evaluations [see ISO 18562 (all parts)].
5.2 Categorization by nature of body contact
5.2.1 Non-contacting medical devices
These include medical devices (or components) that have neither direct nor indirect contact with the
body and where biocompatibility information would not be necessary. Diagnostic software, an in vitro
diagnostic device and a blood-collection tube are examples of non-contact devices.
ISO 10993-1:2018(E)
5.2.2 Surface-contacting medical devices
These include medical devices in contact with the following.
a) Skin
— Medical devices that contact intact skin surfaces only.
EXAMPLES Electrodes, external prostheses, fixation tapes, compression bandages and monitors of
various types.
NOTE Some medical devices used in either sterile or non-sterile environments include components
that can come into contact with a user’s ungloved hands such as human interfaces for electronic
equipment (e.g. computer keyboards, dials or buttons, touch screens, SD cards, USB sticks); housings
for electronic monitors or programmers that can come into contact with any intact skin (e.g. electronic
devices like cell phones, tablets); or components that can come into contact with a user’s gloved hand
(e.g. catheter handles). If these types of components can be shown to be made from materials in common
use for other consumer products with a similar nature of contact, no further biological evaluation is
needed.
b) Mucosal membranes
— Medical devices that contact intact mucosal membranes.
EXAMPLES Contact lenses, urinary catheters, intravaginal and intra-intestinal devices (stomach
tubes, sigmoidoscopes, colonoscopes, gastroscopes), endotracheal tubes, bronchoscopes, some dental
prostheses and orthodontic devices.
c) Breached or compromised surfaces
— Medical devices that contact breached or otherwise comprom
...
Questions, Comments and Discussion
Ask us and Technical Secretary will try to provide an answer. You can facilitate discussion about the standard in here.
Loading comments...