International ISO Standard IS033405 Reference materials Approaches First edition for characterization and assessment 2024-05 of homogeneity and stability Matériaux de reference - Approches pour la caracterisation et I'évaluation de I'homogénéité et la stabilite Reference number IS033405:2024(en) @IS02024 IS0 33405:2024(en) COPYRIGHTPROTECTEDDOCUMENT @IS02024 All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may the internet or an intranet, without prior written permission. Permission can be requested from either IsO at the address below orIso'smemberbodyinthecountryoftherequester. ISO copyright office CP401·Ch.deBlandonnet8 CH-1214 Vernier, Geneva Phone: +41 22 749 01 11 Email: [email protected] Website: www.iso.org Published in Switzerland IS02024-Allrightsreserved IS0 33405:2024(en) Contents Page Foreword. ..vi Introduction. .vii 1 Scope. .1 2 Normative references 1 3 Terms and definitions. 1 4 Symbols. 2 5 Conventions 3 6 Overview of reference material production 3 6.1 General 3 6.2 Summary of project design. 6.3 Acquisition of starting material 5 6.4 Feasibility studies.. 6 6.5 Reference material processing .6 6.6 Homogeneity assessment. 6 6.7 Stability assessment. .6 6.8 Choice of measurement procedures. .7 6.9 Metrological traceability 7 6.10 Characterization and uncertainty evaluation 7 6.11 Commutability assessment. 7 6.12 Transport issues... 6.13 Value assignment. 8 6.14 Stability monitoring 8 6.15 Reference materials produced in repeated batches 8 7 Assessment of homogeneity 8 7.1 Preamble 8 7.2 Need for an experimental homogeneity study .9 7.3 Properties to be studied. .10 7.4 Statistically valid sampling schemes.. .10 7.4.1 Minimum number of units for a homogeneity study .10 7.4.2 Use of statistical power analysis.. 12 7.4.3 Sampling strategies for a homogeneity study 12 7.5 Choice and conduct of the measurement procedure for a homogeneity study 13 7.5.1 Choice of measurement procedure 13 7.5.2 Conduct of measurements for homogeneity studies. 13 7.6 Homogeneity study designs. 15 7.6.1 Objective of a homogeneity study 15 7.6.2 The basic homogeneity study design - measurement in a single run 16 7.6.3 Randomized block design. 17 7.6.4 Balanced nested design .17 7.6.5 Alternative strategies. 17 7.7 Evaluating a homogeneity study .18 7.7.1 Initial inspection for measurement trends and outliers .18 7.7.2 Inspection for processing trends.. .19 7.7.3 Evaluation of the between-unit term - basic design. 19 7.7.4 Evaluation of the between-unit term - randomized block design 20 7.7.5 Evaluation of the between-unit term - balanced nested design .21 7.7.6 Other homogeneity designs and alternative estimation methods .21 7.8 Insufficient repeatability of the measurement procedure. 22 7.9 Within-unit homogeneity 22 7.9.1 Assessing the need for within-unit homogeneity study 22 7.9.2 Testing for significant within-unit heterogeneity. 22 7.9.3 Assessing minimum sample size.... .24 @ IS0 2024 - All rights reserved IS0 33405:2024(en) 7.10 Check for sufficient homogeneity 25 7.11 Uncertainty evaluation from homogeneity studies. 26 8 Assessment and monitoring of stability 26 8.1 Preamble 26 8.2 Assessment of stability .27 8.2.1 Requirement for stability assessment 27 8.2.2 Types of (in)stability.... 27 8.2.3 General methods for assessment of stability 28 8.2.4 Need for experimental study of stability. 28 8.3 Classification of stability studies. 29 8.3.1 General 29 8.3.2 Classification according to conditions of measurement 29 8.3.3 Classification according to stability study duration and conditions 30 8.3.4 Classification by study objective. 30 8.3.5 Designs for different storage and treatment conditions 31 8.4 General requirements for effective stability studies. .32 8.4.1 Overview of requirements. 32 8.4.2 Selection of RM units... 32 8.4.3 Suitable measurement procedure(s) for stability studies .32 8.4.4 Appropriate experimental design .32 8.5 Evaluation of s