TECHNICAL ISO/TR REPORT 10993-22 First edition 2017-07 Biological evaluation of medical devices - Part 22: Guidance on nanomaterials Evaluation biologique des dispositifs medicaux Partie 22: Lignes directrices sur les nanomatériaux Reference number IS0/TR10993-22:2017(E) International Organization for Standardization @ IS0 2017 =ZHEJIANG INST OF STANDARDIZATION C1 5956617 vided by IHS under Not for Resale, 2017/9/11 05:37:11 ted without license from IHS IS0/TR 10993-22:2017(E) COPYRIGHTPROTECTEDDOCUMENT IS0.2017, Published in Switzerland All rights reserved. Unless otherwise specified, 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 Ch. de Blandonnet 8 . CP 401 CH-1214 Vernier, Geneva, Switzerland Tel. +41 22 749 01 11 Fax +4122 749 09 47 [email protected] www.iso.org Intenatinir PrganizationforStandardization ensee-ZHEJIANG INST.OF STANDARDIzARoISQa7 - All rights reserved Not for Resale, 2017/9/11 05:37:11 etworking permitted without license from IHS IS0/TR 10993-22:2017(E) Contents Page Foreword ..V Introduction. ...vi 1 Scope. 2 Normative references 3 Terms and definitions 4 General principles .5 4.1 General considerations .5 4.2 Biological evaluation of nanomaterials .. 6 4.3 Categorization of nanomaterials .6 4.4 Nanomaterial equivalence.. 5 Characterization of nanomaterials 5.1 General considerations. ..8 5.2 Characterization parameters and methods .10 5.3 Use of reference materials .14 6 Sample preparation. .15 6.1 General considerations. .15 6.2 Special considerations for nanostructured materials ..15 6.3 Specialconsiderationsfornano-objects .15 6.4 Identity, storage and stability of stock nanomaterials ..17 6.5 Description of chemical composition of stock and dosing dispersions .17 6.6 Characterization of stock dispersions. .18 6.7 Characterization of dosing solutions prepared from stock dispersions ..18 6.8 Dosemetrics.. .19 6.9 Additional considerations ..19 6.9.1 Endotoxin. ..19 6.9.2 Sterilization ..20 7 Release of nano-objects from medical devices ..21 7.1 Generalconsiderations .21 7.2 Degradation products .22 7.3 Release of nano-objects by wear .22 7.4 In situ processing .22 8 Toxicokinetics. .22 8.1 General considerations 22 8.2 Factors influencing the toxicokinetics 23 8.2.1 Physicochemical properties .23 8.2.2 Biomolecular adsorption. .24 8.2.3 Exposure route. .25 8.2.4 Dose. 25 8.2.5 Species and gender .25 8.2.6 Measurement techniques 26 Toxicological evaluation .26 9 9.1 General considerations .26 9.2 In vitro cytotoxicity testing 27 9.2.1 Generalconsiderations .27 9.2.2 Consideration of nanomaterial interference with the assays .28 9.2.3 Consideration of relevant dose and dose metrics. .28 9.2.4 Consideration of nano-object kinetics 28 9.3 Genotoxicity, carcinogenicity and reproductive toxicity 29 9.3.1 General considerations. .29 9.3.2 In vitro genotoxicitytests .30 9.3.3 In vivo genotoxicity tests. 31 ntemaional oganzation@sS27-All rights reserved iii ISee=ZHEJIANG INST OF STANDARDIZATION C1 5956617 ed without license from IHS Not for Resale, 2017/9/11 05:37:11