PD ISO GUIDE 35:2017 BSl Standards Publication Reference materials Guidance for characterization and assessment of homogeneity and stability bsi. PUBLISHED DOCUMENT PD ISO GUIDE 35:2017 National foreword This Published Document is the UK implementation of ISO GUIDE 35:2017. The UK participation in its preparation was entrusted to Technical Committee RMI/1, Reference Materials. A list of organizations represented on this committee can be obtained on request to its secretary This publication does not purport to include all the necessary provisions of a contract. Users are responsible for its correct application @ The British Standards Institution 2017 Published by BSI Standards Limited 2017 ISBN 978 0 580 86736 1 ICS 71.040.30 Compliance with a British Standard cannot confer immunity from legal obligations. This Published Document was published under the authority of the Standards Policy and Strategy Committee on 31 October 2017 Amendments/corrigenda issued since publication Date Textaffected PD ISO GUIDE 35:2017 GUIDE 35 Fourth edition 2017-08 Reference materials Guidance for characterization and assessment of homogeneity and stability Matériaux de reéference - Lignes directrices pour la caractérisation et I'évaluation de I'homogénéité et de la stabilite Reference number ISO GUIDE 35:2017(E) osi @IS02017 PD ISO GUIDE 35:2017 IS0 GUIDE 35:2017(E) COPYRIGHT PROTECTED DOCUMENT 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 writtenpermission.Permission canberequestedfromeitherIsOattheaddressbelow orIso'smemberbodyinthecountryof the requester. ISO copyright office Ch. de Blandonnet 8 . CP 401 CH-1214 Vernier, Geneva, Switzerland Tel. +41 22 749 01 11 Fax +41 22 749 09 47 [email protected] www.iso.org ii @ IS0 2017 - All rights reserved PD ISO GUIDE 35:2017 IS0 GUIDE 35:2017(E) Contents Page Foreword ..vi Introduction. ..vii 1 Scope. 2 Normative references. 3 Terms and definitions 4 Symbols. ...3 5 Conventions ..4 6 An overview of reference material production ..5 6.1 General. ..5 6.2 Summary of project design ..5 6.3 Acquisition of starting material .6 6.4 Feasibility studies... 6.5 Reference material processing .7 6.6 Homogeneity assessment. 6.7 Stability assessment.. 7 6.8 Choice of measurement procedures 6.9 Metrological traceability .8 6.10 Characterization and uncertainty evaluation .8 6.11 Commutability assessment. .8 6.12 Transport issues .8 6.13 Value assignment. .9 6.14 Stability monitoring. .9 6.15 Reference materials produced in repeated batches ..9 7 Assessment of homogeneity .9 7.1 Preamble... .9 7.2 Need for an experimental homogeneity study ..10 7.3 Properties to be studied. ..11 7.4 Statisticallyvalidsamplingschemes 11 7.4.1 Minimum number of units for a homogeneity study .11 7.4.2 Use of statistical power analysis . ..13 7.4.3 Sampling strategy for a homogeneity study. ..13 7.5 Choice and conduct of the measurement procedure for a homogeneity study ..14 7.5.1 Choice of measurement procedure. ..14 7.5.2 Conduct of measurements for homogeneity studies ..14 7.6 Homogeneity study designs... ..16 7.6.1 Objective of a homogeneity study ..16 7.6.2 The basic homogeneity study design - measurement in a single run ...17 7.6.3 Randomized block design. .18 7.6.4 Balanced nested design. .18 7.6.5 Alternative strategies.. ..19 7.7 Evaluating a homogeneity study ..19 7.7.1 Initial inspection for measurement trends and outliers 19 7.7.2 Inspection for processing trends. .20 7.7.3 Evaluation of the between-unit term - basic design 20 7.7.4 Evaluation of the between-unit term - randomized block design 21 7.7.5 Evaluation of the between-unit term - balanced nested design. .21 7.7.6 Other homogeneity designs and alternative estimation methods .22 7.8 Insufficient repeatability of the measurement procedure. 22 7.9 Within-unit homogeneity .23 7.9.1 Assessing the need for within-unit homogeneity study .23 7.9.2 Testing