SIST EN ISO 10993-1:2010

Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process (ISO 10993-1:2009)

Biološko ovrednotenje medicinskih pripomočkov - 1. del: Ocena in preskušanje znotraj procesa obvladovanja tveganja (ISO 10993-1:2009)

General Information

• Status: Published
• Technical Committee: COVID 19 - COVID 19 - ISO
• Directive: standardi COVID-19 - UPDATE ON THE AVAILABILITY OF CEN, CENELEC, ISO, IEC STANDARDS AND THEIR NATIONAL ADOPTIONS IN RESPONSE TO THE COVID-19 OUTBREAK

Standards Content (Sample)

Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
SLOVENSKI STANDARD
01-januar-2010
1DGRPHãþD
SIST EN ISO 10993-1:2009
%LRORãNRRYUHGQRWHQMHPHGLFLQVNLKSULSRPRþNRYGHO2FHQDLQSUHVNXãDQMH
]QRWUDMSURFHVDREYODGRYDQMDWYHJDQMD,62
Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk
management process (ISO 10993-1:2009)
Biologische Beurteilung von Medizinprodukten - Teil 1: Beurteilung und Prüfungen im
Rahmen eines Risikomanagementsystems (ISO 10993-1:2009)
Évaluation biologique des dispositifs médicaux - Partie 1: Évaluation et essais au sein
d'un processus de gestion du risque (ISO 10993-1:2009)
Ta slovenski standard je istoveten z: EN ISO 10993-1:2009
ICS:
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10

Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10

EUROPEAN STANDARD
EN ISO 10993-1
NORME EUROPÉENNE
EUROPÄISCHE NORM
October 2009
ICS 11.100.20 Supersedes EN ISO 10993-1:2009, June
English Version
Biological evaluation of medical devices - Part 1: Evaluation and
testing within a risk management process (ISO 10993-1:2009)
Évaluation biologique des dispositifs médicaux - Partie 1: Biologische Beurteilung von Medizinprodukten - Teil 1:
Évaluation et essais au sein d'un processus de gestion du Beurteilung und Prüfungen im Rahmen eines
risque (ISO 10993-1:2009) Risikomanagementsystems (ISO 10993-1:2009)
This European Standard was approved by CEN on 17 September 2009.

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 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 Management Centre has the same status as the
official versions.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal,
Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.

EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2009 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 10993-1:2009: E
worldwide for CEN national Members.

Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
EN ISO 10993-1:2009 (E)
Contents Page
Foreword .3
Annex ZA (informative) Relationship between this International Standard and the Essential
Requirements of EU Directive 93/42/EEC on Medical devices .4
Annex ZB (informative) Relationship between this International Standard and the Essential
Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices .5

Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
EN ISO 10993-1:2009 (E)
Foreword
This document (EN ISO 10993-1:2009) has been prepared by Technical Committee ISO/TC 194 "Biological
evaluation of medical devices" in collaboration with Technical Committee CEN/TC 206 “Biological evaluation
of medical devices” the secretariat of which is held by NEN.
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 April 2010, and conflicting national standards shall be withdrawn at the
latest by April 2010.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 10993-1:2009, June.
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 Directives.
For relationship with EU Directives, see informative Annex ZA and ZB, which are integral parts of this
document.
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, Cyprus, Czech
Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia,
Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain,
Sweden, Switzerland and the United Kingdom.
Endorsement notice
The text of ISO 10993-1:2009 has been approved by CEN as a EN ISO 10993-1:2009 without any
modification.
Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
EN ISO 10993-1:2009 (E)
Annex ZA
(informative)
Relationship between this International Standard and the Essential
Requirements of EU Directive 93/42/EEC on Medical devices
This International Standard has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association to provide a means of conforming to Essential Requirements of the
New Approach Directive 93/42/EEC on Medical devices.
Once this International Standard is cited in the Official Journal of the European Union under that Directive and
has been implemented as a national standard in at least one Member State, compliance with the clauses of
this International Standard given in Table ZA.1 confers, within the limits of the scope of this Intenational
Standard, a presumption of conformity with the corresponding Essential Requirements of that Directive and
associated EFTA regulations.
Table ZA.1 — Correspondence between this International Standard and Directive 93/42/EEC on
Medical devices
Essential Requirements (ERs) of
Clause(s)/subclause(s) of this Qualifying remarks/notes
Directive 93/42/EEC on Medical
International Standard
devices
4, 5, 6, 7 Annex I:
7.1, 7.2 and 7.5
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this International Standard.
Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
EN ISO 10993-1:2009 (E)
Annex ZB
(informative)
Relationship between this International Standard and the Essential
Requirements of EU Directive 90/385/EEC on Active Implantable Medical
Devices
This International Standard has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association to provide a means of conforming to Essential Requirements of the
New Approach Directive 90/385/EEC on Active Implantable Medical Devices.
Once this International Standard is cited in the Official Journal of the European Union under that Directive and
has been implemented as a national standard in at least one Member State, compliance with the clauses of
this International Standard given in Table ZB.1 confers, within the limits of the scope of this International
Standard, a presumption of conformity with the corresponding Essential Requirements of that Directive and
associated EFTA regulations.
Table ZB.1 — Correspondence between this European Standard and Directive 90/385/EEC on Active
Implantable Medical Devices
Essential Requirements (ERs) of
Clause(s)/subclause(s) of this Qualifying remarks/notes
Directive 90/385/EEC on Active
International Standard
Implantable Medical Devices
4, 5, 6, 7 Annex I:
Indents 1 and 2 of Clause 9 only

WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this International Standard.

Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10

Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10

INTERNATIONAL ISO
STANDARD 10993-1
Fourth edition
2009-10-15
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 10993-1:2009(E)
©
ISO 2009
Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
ISO 10993-1:2009(E)
PDF disclaimer
This PDF file may contain embedded typefaces. In accordance with Adobe's licensing policy, this file may be printed or viewed but
shall not be edited unless the typefaces which are embedded are licensed to and installed on the computer performing the editing. In
downloading this file, parties accept therein the responsibility of not infringing Adobe's licensing policy. The ISO Central Secretariat
accepts no liability in this area.
Adobe is a trademark of Adobe Systems Incorporated.
Details of the software products used to create this PDF file can be found in the General Info relative to the file; the PDF-creation
parameters were optimized for printing. Every care has been taken to ensure that the file is suitable for use by ISO member bodies. In
the unlikely event that a problem relating to it is found, please inform the Central Secretariat at the address given below.

©  ISO 2009
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means,
electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or
ISO's member body in the country of the requester.
ISO copyright office
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail [e-mail]
Web www.iso.org
Published in Switzerland
ii © ISO 2009 – All rights reserved

Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
ISO 10993-1:2009(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.3
5 Categorization of medical devices .6
5.1 General .6
5.2 Categorization by nature of body contact .6
5.3 Categorization by duration of contact.7
6 Biological evaluation process.8
6.1 Material characterization .8
6.2 Biological evaluation tests .8
7 Interpretation of biological evaluation data and overall biological safety assessment .14
Annex A (informative) Biological evaluation tests .15
Annex B (informative) Guidance on the risk management process.16
Annex C (informative) Suggested procedure for literature review .19
Bibliography.21

Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
ISO 10993-1:2009(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.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
The main task of technical committees is to prepare International Standards. Draft International Standards
adopted by the technical committees are circulated to the member bodies for voting. Publication as an
International Standard requires approval by at least 75 % of the member bodies casting a vote.
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.
ISO 10993-1 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices.
This fourth edition cancels and replaces the third edition (ISO 10993-1:2003), which has been technically
revised.
ISO 10993 consists of the following parts, under the general title Biological evaluation of medical devices:
⎯ Part 1: Evaluation and testing within a risk management process
⎯ Part 2: Animal welfare requirements
⎯ Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity
⎯ Part 4: Selection of tests for interactions with blood
⎯ Part 5: Tests for in vitro cytotoxicity
⎯ Part 6: Tests for local effects after implantation
⎯ Part 7: Ethylene oxide sterilization residuals
⎯ Part 9: Framework for identification and quantification of potential degradation products
⎯ Part 10: Tests for irritation and skin sensitization
⎯ Part 11: Tests for systemic toxicity
⎯ Part 12: Sample preparation and reference materials
⎯ Part 13: Identification and quantification of degradation products from polymeric medical devices
⎯ Part 14: Identification and quantification of degradation products from ceramics
⎯ Part 15: Identification and quantification of degradation products from metals and alloys
iv © ISO 2009 – All rights reserved

Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
ISO 10993-1:2009(E)
⎯ Part 16: Toxicokinetic study design for degradation products and leachables
⎯ Part 17: Establishment of allowable limits for leachable substances
⎯ Part 18: Chemical characterization of materials
⎯ Part 19: Physico-chemical, morphological and topographical characterization of materials (Technical
Specification)
⎯ Part 20: Principles and methods for immunotoxicology testing of medical devices (Technical
Specification)
Future parts will deal with other relevant aspects of biological evaluation.
Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
ISO 10993-1:2009(E)
Introduction
The primary aim of this part of ISO 10993 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 be a guidance document
for the biological evaluation of medical devices within a risk management process, as part of the overall
evaluation and development of each 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. It
must be appreciated that the term “medical device” is wide-ranging and, at one extreme, consists of a single
material, which may exist in more than one physical form, and at the other extreme, of a complex instrument
or piece of apparatus, consisting of numerous components made of more than one material.
ISO 10993 addresses the determination of the effects of medical devices on tissues, mostly in a general way,
rather than in a specific device-type situation. Thus, for a complete biological safety evaluation, it classifies
medical devices according to the nature and duration of their anticipated contact with human tissues when in
use and indicates, in matrices, the biological data sets that are thought to be relevant in the consideration of
each device category.
The range of biological hazards is wide and complex. The tissue interaction with a constituent material alone
cannot be considered in isolation from the overall device design. Thus, in designing a device, the choice of the
best material with respect to its tissue interaction might result in a less functional device, tissue interaction
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.
Tissue interactions 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 device is used in
humans can be adjudged only with caution, as it cannot be unequivocally concluded that the same tissue
reactions 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 role of this part of ISO 10993 is to serve 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 chemical constituent testing and in vitro models,
in situations where these methods yield equally relevant information to that obtained from in vivo models.
It is not intended that ISO 10993 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.
This part of ISO 10993 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 device, its intended use and the current knowledge of
the medical device provided by review of the scientific literature and previous clinical experience.
Annex A contains an informative table that is generally helpful in identifying biological data sets recommended
in the evaluation of medical devices, according to their category of body contact and duration of clinical
exposure. Annex B contains guidance for the application of the risk management process to medical devices
which encompasses biological evaluation.

vi © ISO 2009 – All rights reserved

Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
INTERNATIONAL STANDARD ISO 10993-1:2009(E)

Biological evaluation of medical devices —
Part 1:
Evaluation and testing within a risk management process
1 Scope
This part of ISO 10993 describes:
⎯ the general principles governing the biological evaluation of medical devices within a risk management
process;
⎯ the general categorization of 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 part of ISO 10993 does not cover testing of materials and devices that do not come into direct or indirect
contact with the patient's body, nor does it cover biological hazards arising from any mechanical failure. Other
parts of ISO 10993 cover specific tests, as indicated in the Foreword.
2 Normative references
The following documents are indispensable for the application 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, Biological evaluation of medical devices — Part 2: Animal welfare requirements
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 interaction 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
Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
ISO 10993-1:2009(E)
ISO 10993-11, 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 10993-18:2005, Biological evaluation of medical devices — Part 18: Chemical characterization of
materials
ISO/TS 10993-19, Biological evaluation of medical devices — Part 19: Physico-chemical, morphological and
topographical 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, 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.
3.1
medical device
any instrument, apparatus, implement, machine, appliance, implant, in vitro reagent or calibrator, software,
material 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 purpose(s) of:
⎯ 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 for medical purposes by means of in vitro examination of specimens derived from
the human body,
and which does not achieve its primary intended action in or on the human body by pharmacological,
immunological or metabolic means, but which may be assisted in its function by such means
NOTE 1 This definition has been developed by the Global Harmonization Task Force (GHTF).
[ISO 13485:2003, definition 3.7]
2 © ISO 2009 – All rights reserved

Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
ISO 10993-1:2009(E)
NOTE 2 Products which might be considered to be medical devices in some jurisdictions but for which there is not yet
a harmonized approach, are:
1) aids for disabled/handicapped people;
2) devices for the treatment/diagnosis of diseases and injuries in animals;
3) accessories for medical devices (see Note 4);
4) disinfection substances;
5) devices incorporating animal and human tissues, which might meet the requirements of the above definition but
are subject to different controls.
NOTE 3 Accessories intended specifically by manufacturers to be used together with a “parent” medical device to
enable that medical device to achieve its intended purpose, should be subject to ISO 10993.
NOTE 4 Medical devices are different from drugs/biologics, and their biological evaluation requires a different approach.
NOTE 5 Medical devices can include dental devices.
3.2
material
any synthetic or natural polymer, metal, alloy, ceramic or other non-viable substance, including tissue
rendered non-viable, used as a medical device or any part thereof
3.3
final product
medical device in its “as-used” state, as defined by the manufacturer's specification or labelling
3.4
chemical constituent
any synthetic or natural substance that is used in a process for manufacturing materials and/or medical
devices, such as additives (antioxidants, UV stabilizers, dyestuff, etc.), processing aids (solvents, lubricants,
antifoaming agents, etc.)
3.5
data set
information from a variety of sources necessary to characterize the biological response of a device
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 programme within a risk management process in accordance with
ISO 14971, as set out in Figure 1. Annex B provides guidance on this process. The biological evaluation shall
be planned, carried out, and documented by knowledgeable and experienced professionals. See Annex C for
how to perform a literature review of existing data.
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 safety evaluation.
The evaluation programme shall include documented, informed decisions that assess the
advantages/disadvantages and relevance of:
a) the physical and chemical characteristics of the various candidate materials;
NOTE Where this information is already documented within the risk management for the device it can be included by
reference.
Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
ISO 10993-1:2009(E)
b) any history of clinical use or human exposure data;
c) any existing toxicology and other biological safety data on product and component materials, breakdown
products and metabolites;
d) test procedures.
Evaluation may include both a study of relevant preclinical and clinical experience 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 device under design.
4.2 In the selection of materials to be used in 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
device:
a) the material(s) of manufacture;
b) intended additives, process contaminants and residues (see ISO 10993-7 for ethylene oxide residues);
c) leachable substances (see ISO 10993-17);
d) 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);
e) other components and their interactions in the final product;
f) the performance and characteristics of the final product;
g) physical characteristics of the final product, including but not limited to, porosity, particle size, shape and
surface morphology.
Identification of material chemical constituents and consideration of chemical characterization
(see ISO 10993-18) shall precede any biological testing (see Figure 1).
Physical effects of the device shall be considered if they impact the biocompatibility (see ISO/TS 10993-19).
For implanted devices, in addition to systemic effects, local effects should also be considered for risk
evaluation.
4.4 The choice of tests and the data required in a biological evaluation, and their interpretation, 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 medical device or its constituents to the body,
enabling the categorization of devices to facilitate the selection of appropriate tests (see Clause 5). The rigour
necessary in the biological evaluation is principally determined by the nature, degree, duration and frequency
of the exposure and the hazards identified for the material.
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 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, allergy, genotoxicity,
carcinogenicity (tumorigenicity) and effects on reproduction including teratogenicity.
4 © ISO 2009 – All rights reserved

Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
ISO 10993-1:2009(E)
a
This process only applies to those medical devices that contact the patient's body directly or indirectly.
Figure 1 — Summary of the systematic approach to a biological evaluation of medical
devices as part of a risk management process
Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
ISO 10993-1:2009(E)
4.6 Selection of any in vitro or in vivo tests shall be based on end-use applications. All tests shall be
conducted according to recognised current/valid best laboratory/quality practices, for example Good
Laboratory Practice (GLP) or ISO/IEC 17025, where applicable, and the data shall be evaluated by competent,
informed professionals.
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. Whenever possible, in vitro screening
shall be carried out before in vivo tests are commenced. Test data, complete to the extent that an independent
analysis could be made, shall be retained.
4.7 The materials or final product shall be re-evaluated if any of the following occurs:
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 may produce adverse effects when used in humans.
4.8 The biological evaluation shall take into account the nature and mobility of the chemical constituents in
the materials used to manufacture the device and other information, other non-clinical tests, clinical studies,
and post-market experience for an overall assessment.
5 Categorization of medical devices
5.1 General
Medical devices shall be categorized according to the nature and duration of body contact as described in 5.2
and 5.3. The categorization of medical devices facilitates identification of appropriate data sets (see Annex A).
The evaluation of any device that does not fall into one of the categories described shall follow the general
principles contained in this part of ISO 10993. Certain devices might fall into more than one category, in which
case evaluation appropriate to each category shall be carried out.
5.2 Categorization by nature of body contact
5.2.1 Surface-contacting devices
These include medical devices in contact with the following.
a) Skin
⎯ devices that contact intact skin surfaces only.
EXAMPLES Electrodes, external prostheses, fixation tapes, compression bandages and monitors of various types.
b) Mucosal membranes
⎯ 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.
6 © ISO 2009 – All rights reserved

Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
ISO 10993-1:2009(E)
c) Breached or compromised surfaces
⎯ devices that contact breached or otherwise compromised body surfaces.
EXAMPLES Dressings or healing devices and occlusive patches, for ulcers, burns and granulation tissue.
5.2.2 External communicating devices
External communicating devices shall be categorized according to their contact with the following application
sites:
a) Blood path, indirect
⎯ devices that contact the blood path at one point and serve as a conduit for entry into the vascular
system.
EXAMPLES Solution administration sets, extension sets, transfer sets and blood administration sets.
b) Tissue/bone/dentin
⎯ devices that contact tissue, bone or pulp/dentin systems.
EXAMPLES Laparoscopes, arthroscopes, draining systems, dental cements, dental filling materials and skin staples.
c) Circulating blood
⎯ devices that contact circulating blood.
EXAMPLES Intravascular catheters, temporary pacemaker electrodes, oxygenators, extracorporal oxygenator tubing
and accessories, dialysers, dialysis tubing and accessories, haemoadsorbents and immunoadsorbents.
5.2.3 Implant devices
Implant devices shall be categorized according to their contact with the following application sites:
a) Tissue/bone
⎯ devices principally contacting bone.
EXAMPLES Orthopaedic pins, plates, replacement joints, bone prostheses, bone cements and intra-osseous devices.
⎯ devices principally contacting tissue and tissue fluid.
EXAMPLES Pacemakers, drug supply devices, neuromuscular sensors and simulators, replacement tendons, breast
implants, artificial larynxes, subperiosteal implants, ligation clips and intra-uterine devices.
b) Blood
⎯ devices principally contacting blood.
EXAMPLES Pacemaker electrodes, artificial arteriovenous fistulae, heart valves, vascular grafts, internal drug-delivery
catheters and ventricular assist devices.
5.3 Categorization by duration of contact
Medical devices shall be categorized according to the anticipated duration of contact as follows.
a) Limited exposure (A) – devices whose cumulative single, multiple or repeated use or contact is up to 24 h.
Posebna objava SIST z dovoljenjem CEN, CENELEC, ISO in IEC: Za potrebe zagotavljanja brezplačnega dostopa do vsebin standardov v času epidemije COVID-19.
Samo za branje. Kopiranje in posredovanje prepovedano. © SIST 2020-04-10
ISO 10993-1:2009(E)
b) Prolonged exposure (B) – devices whose cumulative single, multiple or repeated long-term use or contact
is likely to exceed 24 h but not 30 d.
c) Permanent contact (C) – devices whose cumulative single, multiple or repeated long-term use or contact
exceeds 30 d.
If a material or device can be placed in more than one duration category, the more rigorous testing and/or
evaluation considerations shall apply. With multiple exposures to the device, the decision into which category
a device is placed shall take into account the potential cumulative effect, bearing in mind the period of time
over which these exposures occur. If a device is intended to change during its lifetime, as those that are
polymerized and/or biodegraded in situ, separate evaluations shall be conducted for the different device states.
For example, for a biodegradable glue intended to polymerize in situ, the different device states would include
starting components, intermediate reaction products, the fully polymerized material and degradation products.
6 Biological evaluation process
6.1 Material characterization
Material characterization is a crucial first step in the biological evaluation process. The extent of chemical
characterization required depends on what pre-clinical and clinical safety and toxicological data exist, and on
the nature and duration of body contact with the
...