SIST EN ISO 10993-16:2010
(Main)Biological evaluation of medical devices - Part 16: Toxicokinetic study design for degradation products and leachables (ISO 10993-16:2010)
Biological evaluation of medical devices - Part 16: Toxicokinetic study design for degradation products and leachables (ISO 10993-16:2010)
This part of ISO 10993 gives principles on how toxicokinetic studies relevant to medical devices should be designed and performed. Annex A describes the considerations for inclusion of toxicokinetic studies in the biological evaluation of medical devices.
Biologische Beurteilung von Medizinprodukten - Teil 16: Entwurf und Auslegung toxikokinetischer Untersuchungen hinsichtlich Abbauprodukten und Extrakten (ISO 10993-16:2010)
Dieser Teil von ISO 10993 beschreibt Prinzipien dafür, wie toxikokinetische Untersuchungen, die bei Medizinprodukten von Bedeutung sind, entworfen und durchgeführt werden sollten. Anhang A beschreibt die Überlegungen zur Durchführung toxikokinetischer Untersuchungen zur biologischen Beurteilung von Medizinprodukten.
Évaluation biologique des dispositifs médicaux - Partie 16: Conception des études toxicocinétiques des produits de dégradation et des substances relargables (ISO 10993-16:2010)
L'ISO 10993-16:2010 énonce les principes de conception et de mise en œuvre des études toxicocinétiques relatives aux dispositifs médicaux. L'Annexe A décrit les considérations relatives à l'inclusion d'études toxicocinétiques dans l'évaluation biologique des dispositifs médicaux.
Biološko ovrednotenje medicinskih pripomočkov - 16. del: Načrt toksikokinetičnih raziskav razgradnih produktov in izlužnin (ISO 10993-16:2010)
Ta del ISO 10993 podaja načela o načrtu in izvedbi toksikokinetičnih raziskav, pomembnih za medicinske pripomočke. Dodatek A opisuje premisleke o vključitvi toksikokinetičnih raziskav v biološko ovrednotenje medicinskih pripomočkov.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 10993-16:2010
01-junij-2010
1DGRPHãþD
SIST EN ISO 10993-16:2009
%LRORãNRRYUHGQRWHQMHPHGLFLQVNLKSULSRPRþNRYGHO 1DþUWWRNVLNRNLQHWLþQLK
UD]LVNDYUD]JUDGQLKSURGXNWRYLQL]OXåQLQ ,62
Biological evaluation of medical devices - Part 16: Toxicokinetic study design for
degradation products and leachables (ISO 10993-16:2010)
Biologische Beurteilung von Medizinprodukten - Teil 16: Entwurf und Auslegung
toxikokinetischer Untersuchungen hinsichtlich Abbauprodukten und Extrakten (ISO
10993-16:2010)
Évaluation biologique des dispositifs médicaux - Partie 16: Conception des études
toxicocinétiques des produits de dégradation et des substances relargables (ISO 10993-
16:2010)
Ta slovenski standard je istoveten z: EN ISO 10993-16:2010
ICS:
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
SIST EN ISO 10993-16:2010 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
---------------------- Page: 1 ----------------------
SIST EN ISO 10993-16:2010
---------------------- Page: 2 ----------------------
SIST EN ISO 10993-16:2010
EUROPEAN STANDARD
EN ISO 10993-16
NORME EUROPÉENNE
EUROPÄISCHE NORM
February 2010
ICS 11.100.20 Supersedes EN ISO 10993-16:2009
English Version
Biological evaluation of medical devices - Part 16: Toxicokinetic
study design for degradation products and leachables (ISO
10993-16:2010)
Évaluation biologique des dispositifs médicaux - Partie 16: Biologische Beurteilung von Medizinprodukten - Teil 16:
Conception des études toxicocinétiques des produits de Entwurf und Auslegung toxikenitischer Untersuchungen
dégradation et des substances relargables (ISO 10993- hinsichtlich Abbauprodukten und herauslösbaren
16:2010) Bestandteilen (ISO 10993-16:2010)
This European Standard was approved by CEN on 20 January 2010.
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, Croatia, 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
© 2010 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 10993-16:2010: E
worldwide for CEN national Members.
---------------------- Page: 3 ----------------------
SIST EN ISO 10993-16:2010
EN ISO 10993-16:2010 (E)
Contents Page
Foreword .3
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on Medical Devices .4
Annex ZB (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices .5
2
---------------------- Page: 4 ----------------------
SIST EN ISO 10993-16:2010
EN ISO 10993-16:2010 (E)
Foreword
This document (EN ISO 10993-16:2010) has been prepared by Technical Committee ISO/TC 194 "Biological
evaluation of medical devices" in collaboration 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 August 2010, and conflicting national standards shall be withdrawn at
the latest by August 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 10993-16:2009.
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, Croatia, 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 10993-16:2010 has been approved by CEN as a EN ISO 10993-16:2010 without any
modification.
3
---------------------- Page: 5 ----------------------
SIST EN ISO 10993-16:2010
EN ISO 10993-16:2010 (E)
Annex ZA
(informative)
Relationship between this European Standard and the Essential Requirements of EU
Directive 93/42/EEC on Medical Devices
This European 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 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 European Standard, a
presumption of conformity with the corresponding Essential Requirements of that Directive and associated
EFTA regulations.
Table ZA.1 — Correspondence between this European Standard and Directive 93/42/EEC on medical
devices
Clause(s)/sub-clause(s) of this Essential Requirements (ERs) Qualifying remarks/Notes
European Standard of Directive 93/42/EEC
4, 5, Annex A 7.1, 7.2, 7.5 These relevant Essential
Requirements are only partly
addressed in this International
Standard
GENERAL NOTE — Presumption of conformity depends on also complying with all relevant
clauses/subclauses of ISO 10993-1.
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this standard.
4
---------------------- Page: 6 ----------------------
SIST EN ISO 10993-16:2010
EN ISO 10993-16:2010 (E)
Annex ZB
(informative)
Relationship between this European Standard and the Essential Requirements of
EU Directive 90/385/EEC on Active Implantable Medical Devices
This European 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 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
Clause(s)/sub-clause(s) of this Essential Requirements (ERs) Qualifying remarks/Notes
European Standard of Directive 90/385/EEC
4, 5, Annex A 9 (First and second indents only) The first and second indents of
this relevant Essential
Requirement are only partly
addressed in this International
Standard
GENERAL NOTE — Presumption of conformity depends on also complying with all relevant
clauses/subclauses of ISO 10993-1.
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this standard.
5
---------------------- Page: 7 ----------------------
SIST EN ISO 10993-16:2010
---------------------- Page: 8 ----------------------
SIST EN ISO 10993-16:2010
INTERNATIONAL ISO
STANDARD 10993-16
Second edition
2010-02-15
Biological evaluation of medical
devices —
Part 16:
Toxicokinetic study design for
degradation products and leachables
Évaluation biologique des dispositifs médicaux —
Partie 16: Conception des études toxicocinétiques des produits de
dégradation et des substances relargables
Reference number
ISO 10993-16:2010(E)
©
ISO 2010
---------------------- Page: 9 ----------------------
SIST EN ISO 10993-16:2010
ISO 10993-16:2010(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.
COPYRIGHT PROTECTED DOCUMENT
© ISO 2010
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 copyright@iso.org
Web www.iso.org
Published in Switzerland
ii © ISO 2010 – All rights reserved
---------------------- Page: 10 ----------------------
SIST EN ISO 10993-16:2010
ISO 10993-16:2010(E)
Contents Page
Foreword .iv
Introduction.vi
1 Scope.1
2 Normative references.1
3 Terms and definitions .1
4 Principles for design of toxicokinetic studies.3
5 Guidance on test methods .4
5.1 General considerations.4
5.2 Guidance on specific types of test .5
5.2.1 General.5
5.2.2 Absorption.5
5.2.3 Distribution.6
5.2.4 Metabolism and excretion .6
Annex A (normative) Circumstances in which toxicokinetic studies shall be considered.7
Bibliography.8
© ISO 2010 – All rights reserved iii
---------------------- Page: 11 ----------------------
SIST EN ISO 10993-16:2010
ISO 10993-16:2010(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 10993-16 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices.
This second edition cancels and replaces the first edition (ISO 10993-16:1997), 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 2010 – All rights reserved
---------------------- Page: 12 ----------------------
SIST EN ISO 10993-16:2010
ISO 10993-16:2010(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]
© ISO 2010 – All rights reserved v
---------------------- Page: 13 ----------------------
SIST EN ISO 10993-16:2010
ISO 10993-16:2010(E)
Introduction
Toxicokinetics describe the absorption, distribution, metabolism and excretion, with time, of foreign
compounds in the body. Essential to the evaluation of the safety of a medical device is consideration of the
stability of the material(s) in vivo and the disposition of intended and unintended leachables and degradation
products. Toxicokinetic studies can be of value in assessing the safety of materials used in the development
of a medical device or in elucidating the mechanism of observed adverse reactions. Toxicokinetic studies can
also be applicable to medical devices containing active ingredients. The need for and extent of such studies
should be carefully considered based on the nature and duration of contact of the device with the body
(see Annex A). Existing toxicological literature and toxicokinetic data can be sufficient for this consideration.
The potential hazard posed by a medical device can be attributed to the interactions of its components or their
metabolites with the biological system. Medical devices can release leachables (e.g. residual catalysts,
processing aids, residual monomers, fillers, antioxidants, plasticizers) and/or degradation products which
migrate from the material and have the potential to cause adverse effects in the body.
A considerable body of published literature exists on the use of toxicokinetic methods to study the fate of
chemicals in the body (see Bibliography). The methodologies and techniques utilized in such studies form the
basis of the guidance in this part of ISO 10993. Annex A provides a rationale for the use of this part of
ISO 10993.
vi © ISO 2010 – All rights reserved
---------------------- Page: 14 ----------------------
SIST EN ISO 10993-16:2010
INTERNATIONAL STANDARD ISO 10993-16:2010(E)
Biological evaluation of medical devices —
Part 16:
Toxicokinetic study design for degradation products and
leachables
1 Scope
This part of ISO 10993 gives principles on how toxicokinetic studies relevant to medical devices should be
designed and performed. Annex A describes the considerations for inclusion of toxicokinetic studies in the
biological evaluation of medical devices.
2 Normative references
The following referenced 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 10993-1, 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 10993-12, Biological evaluation of medical devices — Part 12: Sample preparation and reference
materials
ISO 10993-17, Biological evaluation of medical devices — Part 17: Establishment of allowable limits for
leachable substances
ISO 10993-18, Biological evaluation of medical devices — Part 18: Chemical characterization of materials
ISO 14971, Medical devices — Application of risk management to medical devices
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 10993-1 and the following apply.
3.1
absorption
process by which a substance enters the blood and/or lymph system
3.2
bioavailability
extent of systemic absorption of specified substance
© ISO 2010 – All rights reserved 1
---------------------- Page: 15 ----------------------
SIST EN ISO 10993-16:2010
ISO 10993-16:2010(E)
3.3
biodegradation
degradation due to the biological environment
NOTE Biodegradation might be modelled by in vitro tests.
3.4
bioresorption
process by which a biomaterial is degraded in the physiological environment and the product(s) eliminated
and/or absorbed
3.5
clearance
rate of removal of a specified substance from the body or parts of the body by metabolism and/or excretion
3.6
c
max
maximum concentration of a specified substance in plasma expressed in mass per unit volume
NOTE When the maximum concentration in fluid or tissue is being referred to, it should have an appropriate identifier,
e.g. c , liver, and be expressed in mass per unit volume or mass.
max
3.7
degradation product
product of a material which is derived from the chemical breakdown of the original material
3.8
distribution
process by which an absorbed substance and/or its metabolites circulate and partition within the body
3.9
excretion
process by which an absorbed substance and/or its metabolites are removed from the body
3.10
extract
liquid that results from extraction of the test substance or control
3.11
half-life
t
1/2
time for the concentration of a specified substance to decrease to 50 % of its initial value in the same body
fluid or tissue
3.12
leachable
chemical that can migrate from a device or component under storage conditions or conditions of use
NOTE A leachable (e.g. additives, monomeric or oligomeric constituent of polymeric material) can be extracted under
laboratory conditions that simulate normal conditions of exposure.
3.13
mean residence time
statistical moment related to half-life which provides a quantitative estimate of the persistence of a specified
substance in the body
2 © ISO 2010 – All rights reserved
---------------------- Page: 16 ----------------------
SIST EN ISO 10993-16:2010
ISO 10993-16:2010(E)
3.14
metabolism
process by which an absorbed substance is structurally changed within the body by enzymatic and/or non-
enzymatic reactions
NOTE The products of the initial reaction can subsequently be modified by either enzymatic or non-enzymatic
reactions prior to excretion.
3.15
test substance
degradation product or leachable used for toxicokinetic study
3.16
t
max
time at which c is observed
max
3.17
volume of distribution
V
d
parameter for a single-compartment model describing the apparent volume which would contain the amount of
test substance in the body if it were uniformly distributed
4 Principles for design of toxicokinetic studies
4.1 Toxicokinetic studies should be designed on a case-by-case basis.
4.2 A study protocol shall be written prior to commencement of the study. The study design, including
methods, shall be defined in this protocol. Details of areas to be defined are given in 4.3 to 4.8 and in
Clause 5.
4.3 The results of leaching studies should be considered in order to determine the methods to be used for
toxicokinetic studies. Information on the chemical and physicochemical properties, surface morphology of the
material and biochemical properties of any leachable should also be considered.
NOTE The extent and rate of release of leachables depend on the concentration at the surface, migration to the
surface within the material, solubility and flow rate in the physiological milieu.
4.4 lt is recommended to undertake toxicokinetic studies with a characterized leachable or degradation
product that has the potential of being toxic. However, the performance of toxicokinetic studies on mixtures is
possible under certain conditions. An extract liquid (see lSO 10993-12), or a ground or powdered form of the
material or device, may be used in exceptional circumstances and shall be justified in the study design.
4.5 Analytical methods shall be able to detect and characterize degradation products, leachables and
metabolites in biological fluids and tissues. For analytical methods, other parts of ISO 10993 shall be used as
relevant. The methods shall be fully described in the study report (see 5.1.11). Quantitative analytical methods
shall be specific, sensitive and reproducible, and produce data which show linearity over the range of
expected analyte concentrations. Validation of the assay method shall be presented in the report.
4.6 The study design shall state the physiological fluid, tissue or excreta in which analyte levels will be
determined.
NOTE Blood is convenient to sample and thus is often the fluid of choice for kinetic parameter and absorption studies.
lt is necessary to specify whether analysis is on whole blood, serum or plasma and to provide validation of this choice.
Binding to circulating proteins or red cells can be determined in vitro.
4.7 The study report should contain information on analyte binding in the sample (e.g. amount and affinity)
and demonstrate that this does not lead to underestimation of analyte concentration.
© ISO 2010 – All rights reserved 3
---------------------- Page: 17 ----------------------
SIST EN ISO 10993-16:2010
ISO 10993-16:2010(E)
4.8 There should be sufficient data points with adequate time intervals to allow determination of kinetic
parameters. ln theory this should cover several terminal half-lives; in practice the constraints of the analytical
method may necessitate a compromise.
5 Guidance on test methods
5.1 General considerations
5.1.1 The study should be performed in an appropriate sex and species. Healthy young adult animals
should be acclimatized to laboratory conditions for at least 7 d. They should be transferred to individual
metabolism cages, when used, for an acclimatization period of at least 24 h. The environmental conditions
should be as recommended in guidelines for the care and use of animals (see ISO 10993-2). During the study,
conventional animal diets and drinking water should be freely available unless otherwise specified in the
protocol. Animals should be randomly selected into groups for each time period studied; group sizes of at
least three for small animals and at least two for larger species should be used. At the appropriate specified
times, animals should be humanely killed.
5.1.2 A non-radiolabelled test substance may be utilized provided suitable validated assay procedures for
the test substance in the relevant samples exist and the metabolism of the test substance is well
characterized.
5.1.3 If necessary, the test substance should be radiolabelled in a metabolically stable position, preferably
14 3 3
with C or H, and of a suitable radiochemical purity (> 97 %). When using H, the possibility of tritium
exchange should be considered. The radiolabelled compound should be diluted, when appropriate, with a
non-radiolabelled substance.
5.1.4 When using a radiolabelled compound, the specific activity and radiochemical purity of the test
substance shall be known.
5.1.5 The test substance should be administered by an appropriate route. This route should be relevant to
the use of the medical device. The test substance should be prepared in a suitable vehicle taking into account
the physicochemical properties of the test substance (leachable or degradation product) using appropriate
route and dose of administration. The stability of the sample under the proposed condition's administration
should be known and reported.
NOTE The study design might require the inclusion of other route(s) for comparison of percent absorption.
5.1.6 In dose balance studies, animals should be housed only in metabolism cages.
5.1.7 Urine and faeces should be collected in low temperature vessels (or in vessels containing
preservative that does not interfere with the analysis) to prevent post-elimination microbial or spontaneous
modification. Blood for whole-blood or plasma analysis should be collected in the presence of a suitable
anticoagulant.
5.1.8 Controls should, wherever possible, be collected prior to dosing. In some studies collection of controls
(e.g. tissues) is not possible from the test animals and these should be obtained from a control group.
5.1.9 Collection times should be appropriate to the type of study being performed, and may be carried out,
as necessary, over periods of minutes, hours, days, weeks or even months. For studies involving excreta, this
is usually 24 h periods over at least 96 h. Where blood sampling is required, blood is collected according to a
specified schedule ranging from minutes to hours over a period up to 72 h.
5.1.10 Toxicokinetic studies should be performed in accordance with good laboratory practice.
4 © ISO 2010 – All rights reserved
---------------------- Page: 18 ----------------------
SIST EN ISO 10993-16:2010
ISO 10993-16:2010(E)
5.1.11 The study report shall include the following information, where relevant:
a) strain and source of animals, age, sex, environmental conditions, diet;
b) test substance and sample, purity, stability, formulation, amount administered;
c) test conditions, including route of administration;
d) assay methods, extraction, detection, validation;
e) overall recovery of material;
f) tabulation of individual results at each time point;
g) quality standard or good laboratory practice compliance statement;
h) discussion of results;
i) interpretation of results.
5.2 Guidance on specific types of test
5.2.1
...
Questions, Comments and Discussion
Ask us and Technical Secretary will try to provide an answer. You can facilitate discussion about the standard in here.