SIST EN ISO 10993-1:2003

SLOVENSKI STANDARD
SIST EN ISO 10993-1:2003
01-november-2003
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SIST EN ISO 10993-1:2000
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Biological evaluation of medical devices - Part 1: Evaluation and testing (ISO 10993-
1:2003)
Biologische Beurteilung von Medizinprodukten Teil 1: Beurteilung und Prüfungen (ISO
10993-1:2003)
Evaluation biologique des dispositifs médicaux - Partie 1: Evaluation et essais (ISO
10993-1:2003)
Ta slovenski standard je istoveten z: EN ISO 10993-1:2003
ICS:
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
SIST EN ISO 10993-1:2003 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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EUROPEAN STANDARD
EN ISO 10993-1
NORME EUROPÉENNE
EUROPÄISCHE NORM
August 2003
ICS 11.100 Supersedes EN ISO 10993-1:1997
English version
Biological evaluation of medical devices - Part 1: Evaluation and
testing (ISO 10993-1:2003)
Evaluation biologique des dispositifs médicaux - Partie 1: Biologische Beurteilung von Medizinprodukten Teil 1:
Evaluation et essais (ISO 10993-1:2003) Beurteilung und Prüfungen (ISO 10993-1:2003)
This European Standard was approved by CEN on 28 July 2003.
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 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 Management Centre has the same status as the official
versions.
CEN members are the national standards bodies of Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece,
Hungary, Iceland, Ireland, Italy, Luxembourg, Malta, Netherlands, Norway, Portugal, Slovakia, Spain, Sweden, Switzerland and United
Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: rue de Stassart, 36  B-1050 Brussels
© 2003 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 10993-1:2003 E
worldwide for CEN national Members.

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EN ISO 10993-1:2003 (E)
CORRECTED  2003-09-24
Foreword
This document (EN ISO 10993-1:2003) has been prepared by Technical Committee ISO/TC 194
"Biological evaluation of medical devices" in collaboration with Technical Committee CEN/TC
206 "Biocompatibility of medical and dental materials and 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 February 2004, and conflicting national
standards shall be withdrawn at the latest by February 2004.
This document supersedes EN ISO 10993-1:1997.
This document has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association, and supports essential requirements of EU
Directive(s).
For relationship with EU Directive(s), see informative Annex ZA, which is an integral part 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, Czech
Republic, Denmark, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy,
Luxembourg, Malta, Netherlands, Norway, Portugal, Slovakia, Spain, Sweden, Switzerland and
the United Kingdom.
Endorsement notice
The text of ISO 10993-1:2003 has been approved by CEN as EN ISO 10993-1:2003 without any
modifications.
2

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EN ISO 10993-1:2003 (E)
Annex ZA
(informative)
Clauses of this European Standard addressing essential requirements or
other provisions of EU Directives
This European Standard has been prepared under a mandate given to CEN by the European
Commission and the European Free Trade Association and supports essential requirements of
EU Directive 93/42/EEC.
WARNING Other requirements and other EU Directives may be applicable to the
product(s) falling within the scope of this standard.
Compliance with these clauses of this standard provides one means of conforming with the
specific essential requirements of the Directive concerned and associated EFTA regulations.
3

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INTERNATIONAL ISO
STANDARD 10993-1
Third edition
2003-08-01


Biological evaluation of medical
devices —
Part 1:
Evaluation and testing
Évaluation biologique des dispositifs médicaux —
Partie 1: Évaluation et essais




Reference number
ISO 10993-1:2003(E)
©
ISO 2003

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ISO 10993-1:2003(E)
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ii © ISO 2003 — All rights reserved

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ISO 10993-1:2003(E)
Contents Page
Foreword. iv
Introduction . vi
1 Scope. 1
2 Terms and definitions. 1
3 General principles applying to biological evaluation of medical devices . 2
4 Categorization of medical devices . 3
5 Testing. 4
6 Selection of biological evaluation tests. 7
7 Assurance of test methods. 8
Annex A (informative) Rationale .11
Annex B (informative) Flow chart to aid in ensuring a systematic approach to biological
evaluation of medical devices . 13
Bibliography . 14

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ISO 10993-1:2003(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 third edition cancels and replaces the second edition (ISO 10993-1:1997), of which it constitutes a minor
revision.
ISO 10993 consists of the following parts, under the general title Biological evaluation of medical devices:
— Part 1: Evaluation and testing
— 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 8: Selection and qualification of reference materials for biological tests
— Part 9: Framework for identification and quantification of potential degradation products
— Part 10: Tests for irritation and delayed-type hypersensitivity
— 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
— Part 16: Toxicokinetic study design for degradation products and leachables
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ISO 10993-1:2003(E)
— Part 17: Establishment of allowable limits for leachable substances
— Part 18: Chemical characterization of materials
Future parts will deal with other relevant aspects of biological testing.
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ISO 10993-1:2003(E)
Introduction
This part of ISO 10993 is a combination/harmonization of numerous international and national standards and
guidelines concerning the biological evaluation of medical devices. It is intended to be the overall guidance
document for the selection of tests enabling evaluation of biological responses relevant to the safety of
medical devices and materials.
The role of this part of ISO 10993 is to serve as a framework in which to plan such a biological evaluation
which minimizes the number and exposure of test animals.
The protection of humans is the primary goal of ISO 10993.
The appropriate selection and interpretation of biological evaluation tests requires an understanding of the
rationale behind such testing. An informative rationale for the use of this part of ISO 10993 is provided in
Annex A. Annex B contains a flow chart to aid in the systematic approach to the biological evaluation of
medical devices. A bibliography is given at the end of the text.

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INTERNATIONAL STANDARD ISO 10993-1:2003(E)

Biological evaluation of medical devices —
Part 1:
Evaluation and testing
1 Scope
This part of ISO 10993 describes
a) the general principles governing the biological evaluation of medical devices;
b) the categorization of devices based on the nature and duration of their contact with the body;
c) the selection of appropriate tests.
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.
NOTE Other parts of ISO 10993 cover specific tests (see also the rationale in A.2).
2 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
2.1
medical device
any instrument, apparatus, appliance, material or other article, including software, whether used alone or in
combination, intended by the manufacturer to be used for human beings solely or principally for the purpose
of:
 diagnosis, prevention, monitoring, treatment or alleviation of disease;
 diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap;
 investigation, replacement or modification of the anatomy or of a physiological process;
 control of conception;
and which does not achieve its principal 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 Devices are different from drugs, and their biological evaluation requires a different approach.
NOTE 2 Use of the term “medical device” includes dental devices.
2.2
material
any synthetic or natural polymer, metal, alloy, ceramic or other nonviable substance, including tissue rendered
nonviable, used as a medical device or any part thereof
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ISO 10993-1:2003(E)
2.3
final product
medical device in its “as-used” state
3 General principles applying to biological evaluation of medical devices
3.1 The selection and evaluation of any material or device intended for use in humans requires a structured
programme of assessment.
In the design process, an informed decision shall be made and documented that weighs the
advantages/disadvantages of the various choices of material and test procedure. To give assurance that the
final product will perform as intended and be safe for human use, the programme shall include a biological
evaluation.
The biological evaluation shall be planned, carried out and documented by knowledgeable and experienced
individuals capable of making informed decisions based on the advantages and disadvantages of the various
materials and test procedures available.
3.2 In the selection of materials to be used in device manufacture, the first consideration should be fitness
for purpose with regard to characteristics and properties of the material, which include chemical, toxicological,
physical, electrical, morphological and mechanical properties.
3.3 The following should be considered for their relevance to the overall biological evaluation of the device:
a) the material(s) of manufacture;
b) intended additives, process contaminants and residues;
c) leachable substances;
d) degradation products;
e) other components and their interactions in the final product;
f) the properties and characteristics of the final product.
NOTE If appropriate, identification and quantification of extractable chemical entities of the final product should
precede biological evaluation (see ISO 10993-9).
3.4 Tests to be used in biological evaluation, and the interpretation of the results of such tests, should take
into account the chemical composition of the materials, including the conditions of exposure and the nature,
degree, frequency and duration of exposure of the device or its constituents to the body. By following these
principles, devices can be categorized to facilitate the selection of appropriate tests (see Clause 4). This part
of ISO 10993 is concerned with the tests to be carried out on materials and/or the final product.
The range of potential biological hazards is wide and may include:
a) short-term effects (e.g. acute toxicity, irritation to the skin, eye and mucosal surfaces, sensitization,
haemolysis and thrombogenicity);
b) long-term or specific toxic effects [e.g. subchronic and chronic toxic effects, sensitization, genotoxicity,
carcinogenicity (tumorigenicity) and effects on reproduction including teratogenicity].
3.5 All potential biological hazards should be considered for every material and final product, but this does
not imply that testing for all potential hazards will be necessary or practical (see Clause 6).
3.6 Any in vitro or in vivo tests shall be based on end-use applications and appropriate good laboratory
practice followed by evaluation by competent informed persons. Whenever possible, in vitro screening should
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ISO 10993-1:2003(E)
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 (see A.2, “Subclause 3.6”).
3.7 The materials or final product shall be considered for biological re-evaluation 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 final product during storage;
d) any change in the intended use of the product;
e) any evidence that the product may produce adverse effects when used in humans.
3.8 The biological evaluation performed in accordance with this part of ISO 10993 should be considered in
conjunction with the nature and mobility of the ingredients 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 (see A.2, “Subclause 3.8”).
4 Categorization of medical devices
4.1 General
Following the general principles laid down in Clause 3, medical devices can be categorized to facilitate the
selection of appropriate tests.
The testing of any device that does not fall into one of the categories described should follow the general
principles contained in this part of ISO 10993. Certain devices may fall into more than one category, in which
case testing appropriate to each category should be considered.
Medical devices shall be categorized according to the nature and duration of body contact as described in 4.2
and 4.3.
4.2 Categorization by nature of body contact
4.2.1 Non-contact devices
Medical devices that do not contact the patient's body directly or indirectly are not included in the scope of
ISO 10993.
4.2.2 Surface-contacting devices
These include medical devices in contact with the following surfaces:
a) skin: devices that contact intact skin surfaces only; examples include electrodes, external prostheses,
fixation tapes, compression bandages and monitors of various types;
b) mucosal membranes: devices that contact intact mucosal membranes; examples include contact lenses,
urinary catheters, intravaginal and intraintestinal devices (stomach tubes, sigmoidoscopes, colonoscopes,
gastroscopes), endotracheal tubes, bronchoscopes, dental prostheses, orthodontic devices and
intrauterine devices;
c) breached or compromised surfaces: devices that contact breached or otherwise compromised body
surfaces; examples include dressings, healing devices and occlusive patches for ulcers, burns and
granulation tissue.
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ISO 10993-1:2003(E)
4.2.3 External communicating devices
These include medical devices in 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 include 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 include
laparoscopes, arthroscopes, draining systems, dental cements, dental filling materials and skin staples;
c) circulating blood: devices that contact circulating blood; examples include intravascular catheters,
temporary pacemaker electrodes, oxygenators, extracorporal oxygenator tubing and accessories,
dialysers, dialysis
...