SIST EN ISO 7405:2019

Dentistry - Evaluation of biocompatibility of medical devices used in dentistry (ISO 7405:2018, Corrected version 2018-12)

This document specifies test methods for the evaluation of biological effects of medical devices used in dentistry. It includes testing of pharmacological agents that are an integral part of the device under test.
This document does not cover testing of materials and devices that do not come into direct or indirect contact with the patient's body.

Zahnheilkunde - Beurteilung der Biokompatibilität von in der Zahnheilkunde verwendeten Medizinprodukten (ISO 7405:2018)

Médecine bucco-dentaire - Évaluation de la biocompatibilité des dispositifs médicaux utilisés en médecine bucco-dentaire (ISO 7405:2018)

Le présent document spécifie des méthodes d'essai pour l'évaluation des effets biologiques des dispositifs médicaux utilisés en médecine bucco-dentaire. Il inclut des essais de produits pharmacologiques qui font partie intégrante du dispositif soumis à essai.
Le présent document ne couvre pas les essais des matériaux et des dispositifs qui n'entrent pas en contact direct ou indirect avec le corps du patient.

Zobozdravstvo - Ovrednotenje biokompatibilnosti medicinskih pripomočkov v zobozdravstvu (ISO 7405:2018, popravljena verzija 2018-12)

Ta dokument določa preskusne metode za ovrednotenje bioloških učinkov medicinskih pripomočkov v zobozdravstvu. Vključuje preskušanje farmakoloških agentov, ki so ključen del pripomočka, ki se preskuša.
Ta dokument ne zajema preskušanja materialov in pripomočkov, ki ne prihajajo v neposreden ali posreden
stik z bolnikovim telesom.

General Information

• Status: Withdrawn
• Public Enquiry End Date: 19-May-2017
• Publication Date: 09-Dec-2018
• Withdrawal Date: 17-Jul-2025
• ICS: 11.060.01 - Dentistry in general
• ICS: 11.100.20 - Biological evaluation of medical devices
• Technical Committee: VAZ - Healthcare
• Current Stage: 9900 - Withdrawal (Adopted Project)
• Start Date: 18-Jul-2025
• Due Date: 10-Aug-2025
• Completion Date: 18-Jul-2025
• Directive: 93/42/EEC - Council Directive 93/42/EEC of 14 June 1993 concerning medical devices
• Ref Project: EN ISO 7405:2018 - Dentistry - Evaluation of biocompatibility of medical devices used in dentistry (ISO 7405:2018, Corrected version 2018-12)

Relations

• Replaces: SIST EN ISO 7405:2009 - Dentistry - Evaluation of biocompatibility of medical devices used in dentistry (ISO 7405:2008)
• Effective Date: 01-Jan-2019
• Replaces: SIST EN ISO 7405:2009/A1:2013 - Dentistry - Evaluation of biocompatibility of medical devices used in dentistry - Amendment 1: Positive control material (ISO 7405:2008/Amd 1:2013)
• Effective Date: 01-Jan-2019
• Replaced By: SIST EN ISO 7405:2025 - Dentistry - Evaluation of biocompatibility of medical devices used in dentistry (ISO 7405:2025)
• Effective Date: 01-Sep-2025

Standards Content (Sample)

SLOVENSKI STANDARD
01-januar-2019
1DGRPHãþD
SIST EN ISO 7405:2009
SIST EN ISO 7405:2009/A1:2013
=RER]GUDYVWYR2YUHGQRWHQMHELRNRPSDWLELOQRVWLPHGLFLQVNLKSULSRPRþNRYY
]RER]GUDYVWYX,62
Dentistry - Evaluation of biocompatibility of medical devices used in dentistry (ISO
7405:2018)
Zahnheilkunde - Beurteilung der Biokompatibilität von in der Zahnheilkunde verwendeten
Medizinprodukten (ISO 7405:2018)
Médecine bucco-dentaire - Évaluation de la biocompatibilité des dispositifs médicaux
utilisés en médecine bucco-dentaire (ISO 7405:2018)
Ta slovenski standard je istoveten z: EN ISO 7405:2018
ICS:
11.060.01 Zobozdravstvo na splošno Dentistry in general
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EN ISO 7405
EUROPEAN STANDARD
NORME EUROPÉENNE
November 2018
EUROPÄISCHE NORM
ICS 11.060.10; 11.100.99 Supersedes EN ISO 7405:2008
English Version
Dentistry - Evaluation of biocompatibility of medical
devices used in dentistry (ISO 7405:2018)
Médecine bucco-dentaire - Évaluation de la Zahnheilkunde - Beurteilung der Biokompatibilität von
biocompatibilité des dispositifs médicaux utilisés en in der Zahnheilkunde verwendeten Medizinprodukten
médecine bucco-dentaire (ISO 7405:2018) (ISO 7405:2018)
This European Standard was approved by CEN on 17 August 2018.

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, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, 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
© 2018 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 7405:2018 E
worldwide for CEN national Members.

Contents Page
European foreword . 3

European foreword
This document (EN ISO 7405:2018) has been prepared by Technical Committee ISO/TC 106 "Dentistry"
in collaboration with Technical Committee CEN/TC 55 “Dentistry” the secretariat of which is held by
DIN.
This European Standard shall be given the status of a national standard, either by publication of an
identical text or by endorsement, at the latest by May 2019, and conflicting national standards shall be
withdrawn at the latest by May 2019.
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 7405:2008.
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, Former Yugoslav Republic of Macedonia,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,
Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and the United Kingdom.
Endorsement notice
The text of ISO 7405:2018 has been approved by CEN as EN ISO 7405:2018 without any modification.

INTERNATIONAL ISO
STANDARD 7405
Third edition
2018-10
Corrected version
2018-12
Dentistry — Evaluation of
biocompatibility of medical devices
used in dentistry
Médecine bucco-dentaire — Évaluation de la biocompatibilité des
dispositifs médicaux utilisés en médecine bucco-dentaire
Reference number
ISO 7405:2018(E)
©
ISO 2018
ISO 7405:2018(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: [phone]
Fax: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland
ii © ISO 2018 – All rights reserved

ISO 7405:2018(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Categorization of medical devices . 2
4.1 Categorization by nature of contact . 2
4.1.1 General. 2
4.1.2 Non-contact devices . 3
4.1.3 Surface-contacting devices . 3
4.1.4 External communicating devices . 3
4.1.5 Implant devices used in dentistry . 3
4.2 Categorization by duration of contact . 3
4.2.1 General. 3
4.2.2 Limited exposure devices . 3
4.2.3 Prolonged exposure devices . 3
4.2.4 Permanent contact devices . 4
5 Biological evaluation process . 4
5.1 General . 4
5.2 Selection of tests and overall assessment . 4
5.3 Selection of test methods . 4
5.4 Types of test . 5
5.4.1 General. 5
5.4.2 Physical and chemical characterization . 5
5.4.3 Group I . 5
5.4.4 Group II . 5
5.4.5 Group III . 6
5.5 Re-evaluation of biocompatibility . 6
6 Test procedures specific to dental materials . 6
6.1 Recommendations for sample preparation . 6
6.1.1 General. 6
6.1.2 General recommendations for sample preparation . 6
6.1.3 Specific recommendations for light curing materials . 7
6.1.4 Specific recommendations for chemically setting materials . 8
6.1.5 Positive control material . 8
6.2 Agar diffusion test . 8
6.2.1 Objective . . 8
6.2.2 Cell line . 8
6.2.3 Culture medium, reagents and equipment . 8
6.2.4 Sample preparation . 9
6.2.5 Controls . 9
6.2.6 Test procedure . 9
6.2.7 Parameters of assessment . 9
6.2.8 Assessment of results .10
6.2.9 Test report .11
6.3 Filter diffusion test .11
6.3.1 Objective . .11
6.3.2 Cell line .11
6.3.3 Culture medium, reagents and equipment .11
6.3.4 Sample preparation .11
6.3.5 Controls .12
6.3.6 Test procedure .12
ISO 7405:2018(E)
6.3.7 Assessment of cell damage.12
6.3.8 Assessment of results .13
6.3.9 Test report .13
6.4 Pulp and dentine usage test .13
6.4.1 Objective . .13
6.4.2 Animals and animal welfare .13
6.4.3 Test procedure .14
6.4.4 Assessment of results .19
6.4.5 Test report .19
6.5 Pulp capping test .19
6.5.1 Objective . .19
6.5.2 Animals and animal welfare .19
6.5.3 Test procedure .20
6.5.4 Assessment of results .22
6.5.5 Test report .22
6.6 Endodontic usage test .22
6.6.1 Objective . .22
6.6.2 Animals and animal welfare .22
6.6.3 Test procedure .22
6.6.4 Assessment of results .24
6.6.5 Test report .25
Annex A (informative) Types of test to be considered for evaluation of biocompatibility of
medical devices used in dentistry .26
Annex B (informative) Dentine barrier cytotoxicity test .29
Annex C (informative) Endosseous dental implant usage test .37
Bibliography .41
iv © ISO 2018 – All rights reserved

ISO 7405:2018(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 106, Dentistry.
This third edition of ISO 7405 cancels and replaces ISO 7405:2008 and ISO/TS 22911:2016 which have
been technically revised. It also incorporates the Amendment ISO 7405:2008/Amd.1:2013.
The main changes compared to the previous edition are as follows:
— as crucial first step in the biological evaluation a material characterization is required before
biological tests are conducted (see 5.4.2)
— modifications of contents of ‘pulp and dentine usage test’ and ‘endodontic test’
— deletion of Annex C (Acute toxicity testing);
— addition of ISO/TS 22911 as new Annex C.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www .iso .org/members .html.
This corrected version of ISO 7405:2018 incorporates the following corrections.
rd rd
—In Table A.1, 3 row, 3 column for “Physical and/or chemical data”, “ISO 10993-18” and “ISO/
TS 10993-19” have been added.
rd th
—In Table A.1, 3 row, 5 column for “Cytotoxicity tests”, “ISO 10993-5” has been added.
rd th
—In Table A.1, 3 row, 11 column for “Genotoxicity”, “ISO 10993-3” has been added.
ISO 7405:2018(E)
Introduction
This document describes the evaluation of the biocompatibility of medical devices used in dentistry. It is
to be used in conjunction with the ISO 10993 series of standards. This document contains special tests,
for which ample experience exists in dentistry and which acknowledge the special needs of dentistry.
Only test methods for which the members of the committee considered there was sufficient published
data have been included. In recommending test methods, the need to minimize the number and exposure
of test animals was given a high priority. It is essential that the decision to undertake tests involving
animals be reached only after a full and careful review of the evidence indicating that a similar outcome
cannot be achieved by other types of test. In order to keep the number of animals required for tests
to an absolute minimum, consistent with achieving the objective indicated, it can be appropriate to
conduct more than one type of test on the same animal at the same time, e.g. pulp and dentine usage
test and pulp capping test. However, in accordance with ISO 10993-2 these tests are performed both
in an efficient and humane way. On all occasions when animal testing is undertaken, such tests are
conducted empathetically and according to standardized procedures as described for each test.
This document does not explicitly describe test methods for occupationally related risks.
Annex B is included to encourage the development of in vitro and ex vivo test methods which will further
reduce the use of animals in the evaluation of the biocompatibility of medical devices used in dentistry.
Annex C is based on and replaces ISO/TS 22911.
vi © ISO 2018 – All rights reserved

INTERNATIONAL STANDARD ISO 7405:2018(E)
Dentistry — Evaluation of biocompatibility of medical
devices used in dentistry
1 Scope
This document specifies test methods for the evaluation of biological effects of medical devices used in
dentistry. It includes testing of pharmacological agents that are an integral part of the device under test.
This document does not cover testing of materials and devices that do not come into direct or indirect
contact with the patient's body.
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 1942, Dentistry — Vocabulary
ISO 6344-1, Coated abrasives — Grain size analysis — Part 1: Grain size distribution test
ISO 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
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 10993-5, 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 10993-10, Biological evaluation of medical devices — Part 10: Tests for irritation and skin sensitization
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 10993-18, 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 14971, Medical devices — Application of risk management to medical devices
ISO 16443, Dentistry — Vocabulary for dental implants systems and related procedure
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 1942, ISO 10993-1,
ISO 10993-12, ISO 16443 and the following apply.
ISO 7405:2018(E)
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https: //www .iso .org/obp
— IEC Electropedia: available at http: //www .electropedia .org/
3.1
dental material
material and/or substance or combination of materials and/or substances specially formulated and
prepared for use in the practice of dentistry and/or associated procedures
3.2
final product
medical device or device component that includes all manufacturing processes for the “to be marketed”
device including packaging and sterilization, if applicable, and that includes processes prior to intended
use, such as mixing, preconditioning and preparation
3.3
positive control material
well characterized material and/or substance that, when evaluated by a specific test method,
demonstrates the suitability of the test system to yield a reproducible, appropriately positive or reactive
response in the test system
3.4
negative control material
well characterized material and/or substance that, when evaluated by a specific test method,
demonstrates the suitability of the test system to yield a reproducible, appropriately negative, non-
reactive or minimal response in the test system
Note 1 to entry: In practice, negative controls include blanks, vehicles/solvents and reference materials (3.5).
3.5
reference material
material with one or more property values that are sufficiently reproducible and well established
to enable use of the material or substance for the calibration of an apparatus, the assessment of a
measurement method or for the assignment of values to materials
Note 1 to entry: For the purpose of this document, a reference material is any well characterized material and/or
substance that, when tested by the procedure described, demonstrates the suitability of the procedure to yield a
reproducible, predictable response. The response may be negative or positive.
3.6
in vitro pulp chamber
device that holds a thin slice of dentine between two chambers and allows fluid and molecules to filter
or to diffuse across the “dentine barrier”
3.7
diffusion
establishment of passive movement of solutes (solubilized constituents) by means of a diffusion gradient
through the “dentine barrier”
4 Categorization of medical devices
4.1 Categorization by nature of contact
4.1.1 General
For the purposes of this document, the classification of medical devices used in dentistry is derived
from ISO 10993-1. If a device or material can be placed in more than one category, the more rigorous
testing requirements shall apply. With multiple exposures the decision into which category a device is
2 © ISO 2018 – All rights reserved

ISO 7405:2018(E)
placed shall take into account the potential cumulative effect, bearing in mind the period of time over
which these exposures occur.
NOTE In this context the term dentistry includes the oromaxillofacial environment.
4.1.2 Non-contact devices
These devices do not contact the patient's body directly or indirectly, and are not included in
ISO 10993-1.
4.1.3 Surface-contacting devices
These devices include those that contact the surface of intact or breached or otherwise compromised
skin, the surface of intact or breached or otherwise compromised oral mucosa, and those that contact
the external surfaces of dental hard tissue, including enamel, dentine and cementum.
NOTE In some circumstances, dentine and cementum are considered as surfaces, e.g. after gingival
recession.
4.1.4 External communicating devices
These devices include dental devices that penetrate and are in contact with oral mucosa, dental hard
tissues, dental pulp tissue or bone, or any combination of these, and are exposed to the oral environment.
NOTE This group also includes any kind of lining or base material to be used under a restoration.
4.1.5 Implant devices used in dentistry
These devices include dental implants and other dental devices that are partially or fully embedded in
one or more of the following:
a) soft tissue, e.g. subperiosteal implants and subdermal implants;
b) bone, e.g. endosteal implants and bone substitutes;
c) pulpodentinal system of the tooth, e.g. endodontic materials;
d) any combination of these, e.g. transosteal implants.
4.2 Categorization by duration of contact
4.2.1 General
For the purposes of this document, medical devices used in dentistry are classified by duration of
contact as described in ISO 10993-1 and listed in 4.2.2 to 4.2.4.
4.2.2 Limited exposure devices
Devices whose cumulative single or multiple use or contact is likely to be up to 24 h.
4.2.3 Prolonged exposure devices
Devices whose cumulative single, multiple or long-term use or contact is likely to exceed 24 h but not 30 d.
ISO 7405:2018(E)
4.2.4 Permanent contact devices
Devices whose cumulative single, multiple or long-term use or contact exceeds 30 d. With multiple
exposures to the device, the decision into which category a device is placed should take into account the
potential cumulative effect, bearing in mind the period of time over which these exposures occur.
NOTE The definition of the term “permanent” is meant to be applied solely for the use of this document. It is
consistent with the definition given in ISO 10993-1.
5 Biological evaluation process
5.1 General
Each medical device used in dentistry shall be subjected to a structured biological evaluation
programme within a risk management process (see ISO 10993-1). Guidance on the implementation of
this programme in ISO 14971 and ISO 10993-1 shall be used.
The biological evaluation programme shall include the review of data sets concerning the biological
properties of each medical device used in dentistry. When this part of the biological evaluation
programme indicates that one or more data sets are incomplete and that further testing is necessary,
the tests shall be selected from the methods described in the ISO 10993 series of standards or in this
document, or in both. If tests that are not included in these International Standards are selected, a
statement shall be made that indicates that the tests described in these International Standards have
been considered and shall include a justification for the selection of other tests.
For combination products the final product shall be evaluated according to this document in conjunction
with any applicable standards.
NOTE 1 In this context, combination products are dental devices of any kind that incorporate, or are intended
to incorporate, as an integral part, a substance that:
a) if used separately, would be a medicine or a biological product;
b) is liable to affect the patient’s body by an ancillary action.
An example would be a bone filling/augmentation device containing a growth factor (i.e. a biological
product).
For combination products, where the device and pharmacological components are packaged separately,
it may be informative to test the device components alone.
All tests shall be conducted according to recognized current/valid best laboratory/quality practices,
where applicable.
NOTE 2 Examples of relevant guidance include GLP (Good Laboratory Practice) or ISO/IEC 17025.
5.2 Selection of tests and overall assessment
The selection of tests and the overall assessment of the results shall be carried out by an expert who
has the appropriate chemical, physical and biological data concerning the device and who is aware of
the intended conditions of use.
5.3 Selection of test methods
The selection of test methods shall be based upon consideration of
a) the intended use of the medical device,
b) the tissue(s) which the medical device may contact, and
4 © ISO 2018 – All rights reserved

ISO 7405:2018(E)
c) the duration of the contact.
If a test selected is not included in the International Standards, a justification for the choice of the
methods shall be included in the test report for each device. If more than one test method in the same
category is recommended by the standards, the selection of one test over the others shall be justified.
5.4 Types of test
5.4.1 General
According to the categorization of the device, tests shall be considered for use as summarized in
Table A.1. This table indicates which types of test method shall be considered, but not that they are
necessarily required to be carried out. A decision not to carry out a type of test identified in Table A.1
shall be justified in the test report on each device. The types of test listed are regarded as a framework
for the evaluation of the biocompatibility of medical devices used in dentistry. For most types of test,
particular methods are identified, although for some devices it is recognized that alternative methods
not included in the International Standards listed can be more appropriate.
5.4.2 Physical and chemical characterization
Material characterization of the medical device or component (see Table A.1) is a crucial first step in the
biological evaluation. Material characterization, if performed, shall be conducted in accordance with
ISO 10993-18 and ISO/TS 10993-19. For nanomaterials, see ISO/TR 10993-22.
For convenience, the types of biological tests have been listed in three groups.
5.4.3 Group I
This group comprises in vitro tests of cytotoxicity. General guidance for in vitro cytotoxicity tests is
presented in ISO 10993-5 and shall be followed. Detailed test protocols for the agar or agarose diffusion
and filter diffusion methods, appropriate to dental materials, are included in this document. The in vitro
cytotoxicity methods include
a) agar diffusion test (see 6.2),
b) filter diffusion test (see 6.3),
c) direct contact or extract tests in accordance with ISO 10993-5, and
d) dentine barrier cytotoxicity test (see Annex B).
NOTE 1 The order of listing does not indicate any preference for one method over another.
NOTE 2 This list does not indicate that all cytotoxicity tests mentioned have to be performed for each medical
device under consideration.
NOTE 3 The use of the dentine barrier cytotoxicity test is encouraged and a description of the test is presented
in Annex B. References to this test are presented in the Bibliography.
5.4.4 Group II
This group comprises tests in accordance with the ISO 10993 series of standards and particular tests,
where appropriate:
a) acute systemic toxicity — oral application — in accordance with ISO 10993-11;
b) acute systemic toxicity — application by inhalation — in accordance with ISO 10993-11;
c) subacute and subchronic systemic toxicity — oral application — in accordance with ISO 10993-11;
d) skin irritation and intracutaneous reactivity in accordance with ISO 10993-10;
ISO 7405:2018(E)
e) delayed-type hypersensitivity in accordance with ISO 10993-10;
f) genotoxicity in accordance with ISO 10993-3;
g) local effects after implantation in accordance with ISO 10993-6.
NOTE 1 In order to allow use of the latest edition of the referenced document only, an undated cross-reference
is possible. An indication of the appropriate clause and subclause is only possible for dated references. Therefore,
the user of this document is requested to check the referenced documents for the appropriate clause numbers.
In the evaluation of materials following local implantation involving mineralized tissues in accordance
with ISO 10993-6, examination of undemineralized sections, in addition to routine demineralized
sections, is recommended.
NOTE 2 If appropriate, the local effects after implantation are evaluated in accordance with dental implant
usage test instead of ISO 10993-6 [see 5.4.5, d)].
5.4.5 Group III
This group comprises tests, specific for medical devices used in dentistry, not referred to in the
ISO 10993 series of standards:
a) pulp and dentine usage test (see 6.4);
b) pulp capping test (see 6.5);
c) endodontic usage test (see 6.6);
d) endosseous dental implant usage test (see Annex C).
Endosseous dental implant usage test is not required, but if applicable, is recommended.
5.5 Re-evaluation of biocompatibility
In accordance with ISO 10993-1, a device shall be considered for re-evaluation of its biocompatibility
as described in 5.4 when revisions or modifications to the formula, quality and/or performance
specifications are made.
NOTE See also ISO 10993-1:2018, B.4.5.1 which provides indications on when to commence a re-evaluation.
6 Test procedures specific to dental materials
6.1 Recommendations for sample preparation
6.1.1 General
These recommendations have been designed for in vitro testing, but can also be used for other purposes,
if suitable.
6.1.2 General recommendations for sample preparation
For the preparation of test samples, consult the respective product standards and/or the manufacturer’s
instructions, and follow those descriptions as closely as possible. Justify any deviation from the
manufacturer's instructions. A detailed description of the sample preparation shall be included in the test
report. Take the following (e.g. environmental) factors into account, considering the final use of the device:
a) temperature;
b) humidity;
6 © ISO 2018 – All rights reserved

ISO 7405:2018(E)
c) light exposure: samples of photosensitive materials shall be produced under the condition that
ambient light does not activate them;
d) material of sample mould: ensure that the material of the sample mould and eventual lubricant
used do not interfere with the setting process of the material;
NOTE Suitable sample mould materials can be semitranslucent or white plastic materials such as
polyethylene or polytetrafluoroethylene (PTFE).
e) oxygen exposure: for materials that produce an oxygen inhibition layer during hardening ensure
that the sample mould is properly sealed during hardening;
f) sterilization: samples shall either be produced under aseptic conditions or be sterilized by the
method appropriate to the material, if necessary and possible; ensure that sterilization does not
affect the material (e.g. sterilization shall not elute substances from material);
g) ratio of sample surface area versus cell layer surface or cell culture medium: document the ratio of
sample surface area versus cell layer surface or cell culture medium; justify the selection of shape
and sample surface area and the applied ratio of sample surface area versus cell layer surface or
cell culture medium;
h) extracts: if extracts are required for a test procedure, prepare extract samples in accordance with
ISO 10993-12:2012, Clause 10.
6.1.3 Specific recommendations for light curing materials
Take the following factors into account, considering the final use of the light curing material:
a) material of sample mould: the reflection coefficient of materials used for sample moulds should
be as close as possible to that of dentine in order to simulate the clinical situation;
NOTE Suitable sample mould materials can be semitranslucent or white plastic materials such as
polyethylene or PTFE.
b) light exposure: light curing shall be done to simulate clinical usage as closely as possible. The
manufacturer's instructions for use shall be followed to provide the same level of curing as would
be the case in actual usage. This will often require curing from one side only but will sometimes
entail a two-sided cure. The cure method is material and/or process specific. Where fully cured test
samples are required for testing, it is important to ensure that the test samples are homogeneous
after removal from the mould. In the case of one-component materials, there shall be no voids, clefts
or air-bubbles present when viewed without magnification. Reference shall be made to the light
source used (light intensity, curing time, spectral distribution of curing light and type of curing
light shall be documented). Care shall be taken to ensure that the light source is recommended for
the materials to be tested and that it is in a satisfactory operating condition;
c) oxygen exposure: for materials that produce an oxygen inhibition layer during light curing, both
ends of the mould shall be covered with transparent oxygen barrier m
...

SLOVENSKI STANDARD
01-januar-2019
Nadomešča:
SIST EN ISO 7405:2009
SIST EN ISO 7405:2009/A1:2013
Zobozdravstvo - Ovrednotenje biokompatibilnosti medicinskih pripomočkov v
zobozdravstvu (ISO 7405:2018, popravljena verzija 2018-12)
Dentistry - Evaluation of biocompatibility of medical devices used in dentistry (ISO
7405:2018, Corrected version 2018-12)
Zahnheilkunde - Beurteilung der Biokompatibilität von in der Zahnheilkunde verwendeten
Medizinprodukten (ISO 7405:2018)
Médecine bucco-dentaire - Évaluation de la biocompatibilité des dispositifs médicaux
utilisés en médecine bucco-dentaire (ISO 7405:2018)
Ta slovenski standard je istoveten z: EN ISO 7405:2018
ICS:
11.060.01 Zobozdravstvo na splošno Dentistry in general
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 7405
EUROPEAN STANDARD
NORME EUROPÉENNE
November 2018
EUROPÄISCHE NORM
ICS 11.060.10; 11.100.99 Supersedes EN ISO 7405:2008
English Version
Dentistry - Evaluation of biocompatibility of medical
devices used in dentistry (ISO 7405:2018, Corrected
version 2018-12)
Médecine bucco-dentaire - Évaluation de la Zahnheilkunde - Beurteilung der Biokompatibilität von
biocompatibilité des dispositifs médicaux utilisés en in der Zahnheilkunde verwendeten Medizinprodukten
médecine bucco-dentaire (ISO 7405:2018) (ISO 7405:2018)
This European Standard was approved by CEN on 17 August 2018.

This European Standard was corrected and reissued by the CEN-CENELEC Management Centre on 19 December 2018.

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, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATIO N

EUROPÄISCHES KOMITEE FÜR NOR M UN G

CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2018 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 7405:2018 E
worldwide for CEN national Members.

Contents Page
European foreword . 3

European foreword
This document (EN ISO 7405:2018) has been prepared by Technical Committee ISO/TC 106 "Dentistry"
in collaboration with Technical Committee CEN/TC 55 “Dentistry” the secretariat of which is held by
DIN.
This European Standard shall be given the status of a national standard, either by publication of an
identical text or by endorsement, at the latest by May 2019, and conflicting national standards shall be
withdrawn at the latest by May 2019.
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 7405:2008.
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, Former Yugoslav Republic of Macedonia,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,
Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and the United Kingdom.
Endorsement notice
The text of ISO 7405:2018, Corrected version 2018-12 has been approved by CEN as EN ISO 7405:2018
without any modification.
INTERNATIONAL ISO
STANDARD 7405
Third edition
2018-10
Corrected version
2018-12
Dentistry — Evaluation of
biocompatibility of medical devices
used in dentistry
Médecine bucco-dentaire — Évaluation de la biocompatibilité des
dispositifs médicaux utilisés en médecine bucco-dentaire
Reference number
ISO 7405:2018(E)
©
ISO 2018
ISO 7405:2018(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: [phone]
Fax: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland
ii © ISO 2018 – All rights reserved

ISO 7405:2018(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Categorization of medical devices . 2
4.1 Categorization by nature of contact . 2
4.1.1 General. 2
4.1.2 Non-contact devices . 3
4.1.3 Surface-contacting devices . 3
4.1.4 External communicating devices . 3
4.1.5 Implant devices used in dentistry . 3
4.2 Categorization by duration of contact . 3
4.2.1 General. 3
4.2.2 Limited exposure devices . 3
4.2.3 Prolonged exposure devices . 3
4.2.4 Permanent contact devices . 4
5 Biological evaluation process . 4
5.1 General . 4
5.2 Selection of tests and overall assessment . 4
5.3 Selection of test methods . 4
5.4 Types of test . 5
5.4.1 General. 5
5.4.2 Physical and chemical characterization . 5
5.4.3 Group I . 5
5.4.4 Group II . 5
5.4.5 Group III . 6
5.5 Re-evaluation of biocompatibility . 6
6 Test procedures specific to dental materials . 6
6.1 Recommendations for sample preparation . 6
6.1.1 General. 6
6.1.2 General recommendations for sample preparation . 6
6.1.3 Specific recommendations for light curing materials . 7
6.1.4 Specific recommendations for chemically setting materials . 8
6.1.5 Positive control material . 8
6.2 Agar diffusion test . 8
6.2.1 Objective . . 8
6.2.2 Cell line . 8
6.2.3 Culture medium, reagents and equipment . 8
6.2.4 Sample preparation . 9
6.2.5 Controls . 9
6.2.6 Test procedure . 9
6.2.7 Parameters of assessment . 9
6.2.8 Assessment of results .10
6.2.9 Test report .11
6.3 Filter diffusion test .11
6.3.1 Objective . .11
6.3.2 Cell line .11
6.3.3 Culture medium, reagents and equipment .11
6.3.4 Sample preparation .11
6.3.5 Controls .12
6.3.6 Test procedure .12
ISO 7405:2018(E)
6.3.7 Assessment of cell damage.12
6.3.8 Assessment of results .13
6.3.9 Test report .13
6.4 Pulp and dentine usage test .13
6.4.1 Objective . .13
6.4.2 Animals and animal welfare .13
6.4.3 Test procedure .14
6.4.4 Assessment of results .19
6.4.5 Test report .19
6.5 Pulp capping test .19
6.5.1 Objective . .19
6.5.2 Animals and animal welfare .19
6.5.3 Test procedure .20
6.5.4 Assessment of results .22
6.5.5 Test report .22
6.6 Endodontic usage test .22
6.6.1 Objective . .22
6.6.2 Animals and animal welfare .22
6.6.3 Test procedure .22
6.6.4 Assessment of results .24
6.6.5 Test report .25
Annex A (informative) Types of test to be considered for evaluation of biocompatibility of
medical devices used in dentistry .26
Annex B (informative) Dentine barrier cytotoxicity test .29
Annex C (informative) Endosseous dental implant usage test .37
Bibliography .41
iv © ISO 2018 – All rights reserved

ISO 7405:2018(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 106, Dentistry.
This third edition of ISO 7405 cancels and replaces ISO 7405:2008 and ISO/TS 22911:2016 which have
been technically revised. It also incorporates the Amendment ISO 7405:2008/Amd.1:2013.
The main changes compared to the previous edition are as follows:
— as crucial first step in the biological evaluation a material characterization is required before
biological tests are conducted (see 5.4.2)
— modifications of contents of ‘pulp and dentine usage test’ and ‘endodontic test’
— deletion of Annex C (Acute toxicity testing);
— addition of ISO/TS 22911 as new Annex C.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www .iso .org/members .html.
This corrected version of ISO 7405:2018 incorporates the following corrections.
rd rd
—In Table A.1, 3 row, 3 column for “Physical and/or chemical data”, “ISO 10993-18” and “ISO/
TS 10993-19” have been added.
rd th
—In Table A.1, 3 row, 5 column for “Cytotoxicity tests”, “ISO 10993-5” has been added.
rd th
—In Table A.1, 3 row, 11 column for “Genotoxicity”, “ISO 10993-3” has been added.
ISO 7405:2018(E)
Introduction
This document describes the evaluation of the biocompatibility of medical devices used in dentistry. It is
to be used in conjunction with the ISO 10993 series of standards. This document contains special tests,
for which ample experience exists in dentistry and which acknowledge the special needs of dentistry.
Only test methods for which the members of the committee considered there was sufficient published
data have been included. In recommending test methods, the need to minimize the number and exposure
of test animals was given a high priority. It is essential that the decision to undertake tests involving
animals be reached only after a full and careful review of the evidence indicating that a similar outcome
cannot be achieved by other types of test. In order to keep the number of animals required for tests
to an absolute minimum, consistent with achieving the objective indicated, it can be appropriate to
conduct more than one type of test on the same animal at the same time, e.g. pulp and dentine usage
test and pulp capping test. However, in accordance with ISO 10993-2 these tests are performed both
in an efficient and humane way. On all occasions when animal testing is undertaken, such tests are
conducted empathetically and according to standardized procedures as described for each test.
This document does not explicitly describe test methods for occupationally related risks.
Annex B is included to encourage the development of in vitro and ex vivo test methods which will further
reduce the use of animals in the evaluation of the biocompatibility of medical devices used in dentistry.
Annex C is based on and replaces ISO/TS 22911.
vi © ISO 2018 – All rights reserved

INTERNATIONAL STANDARD ISO 7405:2018(E)
Dentistry — Evaluation of biocompatibility of medical
devices used in dentistry
1 Scope
This document specifies test methods for the evaluation of biological effects of medical devices used in
dentistry. It includes testing of pharmacological agents that are an integral part of the device under test.
This document does not cover testing of materials and devices that do not come into direct or indirect
contact with the patient's body.
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 1942, Dentistry — Vocabulary
ISO 6344-1, Coated abrasives — Grain size analysis — Part 1: Grain size distribution test
ISO 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
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 10993-5, 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 10993-10, Biological evaluation of medical devices — Part 10: Tests for irritation and skin sensitization
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 10993-18, 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 14971, Medical devices — Application of risk management to medical devices
ISO 16443, Dentistry — Vocabulary for dental implants systems and related procedure
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 1942, ISO 10993-1,
ISO 10993-12, ISO 16443 and the following apply.
ISO 7405:2018(E)
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https: //www .iso .org/obp
— IEC Electropedia: available at http: //www .electropedia .org/
3.1
dental material
material and/or substance or combination of materials and/or substances specially formulated and
prepared for use in the practice of dentistry and/or associated procedures
3.2
final product
medical device or device component that includes all manufacturing processes for the “to be marketed”
device including packaging and sterilization, if applicable, and that includes processes prior to intended
use, such as mixing, preconditioning and preparation
3.3
positive control material
well characterized material and/or substance that, when evaluated by a specific test method,
demonstrates the suitability of the test system to yield a reproducible, appropriately positive or reactive
response in the test system
3.4
negative control material
well characterized material and/or substance that, when evaluated by a specific test method,
demonstrates the suitability of the test system to yield a reproducible, appropriately negative, non-
reactive or minimal response in the test system
Note 1 to entry: In practice, negative controls include blanks, vehicles/solvents and reference materials (3.5).
3.5
reference material
material with one or more property values that are sufficiently reproducible and well established
to enable use of the material or substance for the calibration of an apparatus, the assessment of a
measurement method or for the assignment of values to materials
Note 1 to entry: For the purpose of this document, a reference material is any well characterized material and/or
substance that, when tested by the procedure described, demonstrates the suitability of the procedure to yield a
reproducible, predictable response. The response may be negative or positive.
3.6
in vitro pulp chamber
device that holds a thin slice of dentine between two chambers and allows fluid and molecules to filter
or to diffuse across the “dentine barrier”
3.7
diffusion
establishment of passive movement of solutes (solubilized constituents) by means of a diffusion gradient
through the “dentine barrier”
4 Categorization of medical devices
4.1 Categorization by nature of contact
4.1.1 General
For the purposes of this document, the classification of medical devices used in dentistry is derived
from ISO 10993-1. If a device or material can be placed in more than one category, the more rigorous
testing requirements shall apply. With multiple exposures the decision into which category a device is
2 © ISO 2018 – All rights reserved

ISO 7405:2018(E)
placed shall take into account the potential cumulative effect, bearing in mind the period of time over
which these exposures occur.
NOTE In this context the term dentistry includes the oromaxillofacial environment.
4.1.2 Non-contact devices
These devices do not contact the patient's body directly or indirectly, and are not included in
ISO 10993-1.
4.1.3 Surface-contacting devices
These devices include those that contact the surface of intact or breached or otherwise compromised
skin, the surface of intact or breached or otherwise compromised oral mucosa, and those that contact
the external surfaces of dental hard tissue, including enamel, dentine and cementum.
NOTE In some circumstances, dentine and cementum are considered as surfaces, e.g. after gingival
recession.
4.1.4 External communicating devices
These devices include dental devices that penetrate and are in contact with oral mucosa, dental hard
tissues, dental pulp tissue or bone, or any combination of these, and are exposed to the oral environment.
NOTE This group also includes any kind of lining or base material to be used under a restoration.
4.1.5 Implant devices used in dentistry
These devices include dental implants and other dental devices that are partially or fully embedded in
one or more of the following:
a) soft tissue, e.g. subperiosteal implants and subdermal implants;
b) bone, e.g. endosteal implants and bone substitutes;
c) pulpodentinal system of the tooth, e.g. endodontic materials;
d) any combination of these, e.g. transosteal implants.
4.2 Categorization by duration of contact
4.2.1 General
For the purposes of this document, medical devices used in dentistry are classified by duration of
contact as described in ISO 10993-1 and listed in 4.2.2 to 4.2.4.
4.2.2 Limited exposure devices
Devices whose cumulative single or multiple use or contact is likely to be up to 24 h.
4.2.3 Prolonged exposure devices
Devices whose cumulative single, multiple or long-term use or contact is likely to exceed 24 h but not 30 d.
ISO 7405:2018(E)
4.2.4 Permanent contact devices
Devices whose cumulative single, multiple or long-term use or contact exceeds 30 d. With multiple
exposures to the device, the decision into which category a device is placed should take into account the
potential cumulative effect, bearing in mind the period of time over which these exposures occur.
NOTE The definition of the term “permanent” is meant to be applied solely for the use of this document. It is
consistent with the definition given in ISO 10993-1.
5 Biological evaluation process
5.1 General
Each medical device used in dentistry shall be subjected to a structured biological evaluation
programme within a risk management process (see ISO 10993-1). Guidance on the implementation of
this programme in ISO 14971 and ISO 10993-1 shall be used.
The biological evaluation programme shall include the review of data sets concerning the biological
properties of each medical device used in dentistry. When this part of the biological evaluation
programme indicates that one or more data sets are incomplete and that further testing is necessary,
the tests shall be selected from the methods described in the ISO 10993 series of standards or in this
document, or in both. If tests that are not included in these International Standards are selected, a
statement shall be made that indicates that the tests described in these International Standards have
been considered and shall include a justification for the selection of other tests.
For combination products the final product shall be evaluated according to this document in conjunction
with any applicable standards.
NOTE 1 In this context, combination products are dental devices of any kind that incorporate, or are intended
to incorporate, as an integral part, a substance that:
a) if used separately, would be a medicine or a biological product;
b) is liable to affect the patient’s body by an ancillary action.
An example would be a bone filling/augmentation device containing a growth factor (i.e. a biological
product).
For combination products, where the device and pharmacological components are packaged separately,
it may be informative to test the device components alone.
All tests shall be conducted according to recognized current/valid best laboratory/quality practices,
where applicable.
NOTE 2 Examples of relevant guidance include GLP (Good Laboratory Practice) or ISO/IEC 17025.
5.2 Selection of tests and overall assessment
The selection of tests and the overall assessment of the results shall be carried out by an expert who
has the appropriate chemical, physical and biological data concerning the device and who is aware of
the intended conditions of use.
5.3 Selection of test methods
The selection of test methods shall be based upon consideration of
a) the intended use of the medical device,
b) the tissue(s) which the medical device may contact, and
4 © ISO 2018 – All rights reserved

ISO 7405:2018(E)
c) the duration of the contact.
If a test selected is not included in the International Standards, a justification for the choice of the
methods shall be included in the test report for each device. If more than one test method in the same
category is recommended by the standards, the selection of one test over the others shall be justified.
5.4 Types of test
5.4.1 General
According to the categorization of the device, tests shall be considered for use as summarized in
Table A.1. This table indicates which types of test method shall be considered, but not that they are
necessarily required to be carried out. A decision not to carry out a type of test identified in Table A.1
shall be justified in the test report on each device. The types of test listed are regarded as a framework
for the evaluation of the biocompatibility of medical devices used in dentistry. For most types of test,
particular methods are identified, although for some devices it is recognized that alternative methods
not included in the International Standards listed can be more appropriate.
5.4.2 Physical and chemical characterization
Material characterization of the medical device or component (see Table A.1) is a crucial first step in the
biological evaluation. Material characterization, if performed, shall be conducted in accordance with
ISO 10993-18 and ISO/TS 10993-19. For nanomaterials, see ISO/TR 10993-22.
For convenience, the types of biological tests have been listed in three groups.
5.4.3 Group I
This group comprises in vitro tests of cytotoxicity. General guidance for in vitro cytotoxicity tests is
presented in ISO 10993-5 and shall be followed. Detailed test protocols for the agar or agarose diffusion
and filter diffusion methods, appropriate to dental materials, are included in this document. The in vitro
cytotoxicity methods include
a) agar diffusion test (see 6.2),
b) filter diffusion test (see 6.3),
c) direct contact or extract tests in accordance with ISO 10993-5, and
d) dentine barrier cytotoxicity test (see Annex B).
NOTE 1 The order of listing does not indicate any preference for one method over another.
NOTE 2 This list does not indicate that all cytotoxicity tests mentioned have to be performed for each medical
device under consideration.
NOTE 3 The use of the dentine barrier cytotoxicity test is encouraged and a description of the test is presented
in Annex B. References to this test are presented in the Bibliography.
5.4.4 Group II
This group comprises tests in accordance with the ISO 10993 series of standards and particular tests,
where appropriate:
a) acute systemic toxicity — oral application — in accordance with ISO 10993-11;
b) acute systemic toxicity — application by inhalation — in accordance with ISO 10993-11;
c) subacute and subchronic systemic toxicity — oral application — in accordance with ISO 10993-11;
d) skin irritation and intracutaneous reactivity in accordance with ISO 10993-10;
ISO 7405:2018(E)
e) delayed-type hypersensitivity in accordance with ISO 10993-10;
f) genotoxicity in accordance with ISO 10993-3;
g) local effects after implantation in accordance with ISO 10993-6.
NOTE 1 In order to allow use of the latest edition of the referenced document only, an undated cross-reference
is possible. An indication of the appropriate clause and subclause is only possible for dated references. Therefore,
the user of this document is requested to check the referenced documents for the appropriate clause numbers.
In the evaluation of materials following local implantation involving mineralized tissues in accordance
with ISO 10993-6, examination of undemineralized sections, in addition to routine demineralized
sections, is recommended.
NOTE 2 If appropriate, the local effects after implantation are evaluated in accordance with dental implant
usage test instead of ISO 10993-6 [see 5.4.5, d)].
5.4.5 Group III
This group comprises tests, specific for medical devices used in dentistry, not referred to in the
ISO 10993 series of standards:
a) pulp and dentine usage test (see 6.4);
b) pulp capping test (see 6.5);
c) endodontic usage test (see 6.6);
d) endosseous dental implant usage test (see Annex C).
Endosseous dental implant usage test is not required, but if applicable, is recommended.
5.5 Re-evaluation of biocompatibility
In accordance with ISO 10993-1, a device shall be considered for re-evaluation of its biocompatibility
as described in 5.4 when revisions or modifications to the formula, quality and/or performance
specifications are made.
NOTE See also ISO 10993-1:2018, B.4.5.1 which provides indications on when to commence a re-evaluation.
6 Test procedures specific to dental materials
6.1 Recommendations for sample preparation
6.1.1 General
These recommendations have been designed for in vitro testing, but can also be used for other purposes,
if suitable.
6.1.2 General recommendations for sample preparation
For the preparation of test samples, consult the respective product standards and/or the manufacturer’s
instructions, and follow those descriptions as closely as possible. Justify any deviation from the
manufacturer's instructions. A detailed description of the sample preparation shall be included in the test
report. Take the following (e.g. environmental) factors into account, considering the final use of the device:
a) temperature;
b) humidity;
6 © ISO 2018 – All rights reserved

ISO 7405:2018(E)
c) light exposure: samples of photosensitive materials shall be produced under the condition that
ambient light does not activate them;
d) material of sample mould: ensure that the material of the sample mould and eventual lubricant
used do not interfere with the setting process of the material;
NOTE Suitable sample mould materials can be semitranslucent or white plastic materials such as
polyethylene or polytetrafluoroethylene (PTFE).
e) oxygen exposure: for materials that produce an oxygen inhibition layer during hardening ensure
that the sample mould is properly sealed during hardening;
f) sterilization: samples shall either be produced under aseptic conditions or be sterilized by the
method appropriate to the material, if necessary and possible; ensure that sterilization does not
affect the material (e.g. sterilization shall not elute substances from material);
g) ratio of sample surface area versus cell layer surface or cell culture medium: document the ratio of
sample surface area versus cell layer surface or cell culture medium; justify the selection of shape
and sample surface area and the applied ratio of sample surface area versus cell layer surface or
cell culture medium;
h) extracts: if extracts are required for a test procedure, prepare extract samples in accordance with
ISO 10993-12:2012, Clause 10.
6.1.3 Specific recommendations for light curing materials
Take the following factors into account, considering the final use of the light curing material:
a) material of sample mould: the reflection coefficient of materials used for sample moulds should
be as close as possible to that of dentine in order to simulate the clinical situation;
NOTE Suitable sample mould materials can be semitranslucent or white plastic materials such as
polyethylene or PTFE.
b) light exposure: light curing shall be done to simulate clinical usage as closely as possible. The
manufacturer's instructions for use shall be followed to provide the same level of curing as would
be the case in actual usage. This will often require curing from one side only but will sometimes
entail a two-sided cure. The cure method is material and/or process specific. Where fully cured test
samples are required for testing, it is important to ensure that the test samples are homogeneous
after removal from the mould. In the case of one-component materials, there shall be no voids, clefts
or air-bubbles present when viewed without magnification. Reference shall be made to the light
source used (light intensity, curing time, spectral distribution of curing light and type of curing
light shall be documented). Care shall be taken to ensure that the light source is recommended for
the materials to be tested and that it is in
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