Technical Note 17 - Guidelines for the validation and verification of quantitative and qualitative test methods
June 2012
Page 3 of 32
Guidelines for the validation and verification of
quantitative and qualitative test methods
Table of Contents
1.
Introduction.......................................................................................................................................... 4
2.
Verification of previously validated methods ....................................................................................... 4
3.
Method validation and validation parameters ..................................................................................... 5
3.1
Range in which the calibration equation applies (linearity of calibration) .................................... 8
3.1.1
Measuring interval ................................................................................................................... 9
3.1.2
Matrix effects ........................................................................................................................... 9
3.2
Selectivity ................................................................................................................................... 10
3.3
Sensitivity ................................................................................................................................... 11
3.4
Accuracy .................................................................................................................................... 13
3.4.1
Precision ................................................................................................................................ 13
3.4.1.1
Repeatability...................................................................................................................... 14
3.4.1.2
Reproducibility................................................................................................................... 15
3.4.2
Trueness................................................................................................................................ 15
3.5
Limit of detection and limit of quantitation.................................................................................. 16
3.5.1 The limit of detection (LOD)......................................................................................................... 17
3.5.1.1 LOD based on visual evaluation ........................................................................................... 17
3.5.1.2 LOD based on the standard deviation of the blank............................................................... 17
3.5.1.3 LOD based on the range in which the calibration equation applies...................................... 18
3.5.1.4 LOD based on signal-to-noise............................................................................................... 18
3.5.2 The limit of quantitation (LOQ)..................................................................................................... 18
3.5.2.1 The limit of reporting (LOR)................................................................................................... 18
3.6
Ruggedness ............................................................................................................................... 18
3.7
Measurement Uncertainty.......................................................................................................... 19
3.8
Summary.................................................................................................................................... 20
4
Validation of non-routine methods ........................................................................................................ 21
5
Validation and verification of subjective methods................................................................................. 21
Validation Parameters .............................................................................................................................. 22
5.1
Repeatability/reproducibility (i.e. reliability)................................................................................ 22
5.2
Probability of detection and/or potential error rate..................................................................... 22
Control Measures ..................................................................................................................................... 23
5.3
Critical (or risk) analysis............................................................................................................. 23
5.4
Collaborative exercises.............................................................................................................. 23
5.5
Quality control ............................................................................................................................ 23
5.6
Competence of staff................................................................................................................... 23
5.7
Level of acceptance of the test method ..................................................................................... 23
6.
Glossary of terms .............................................................................................................................. 24
7.
References ........................................................................................................................................ 28
8.
Additional reading.............................................................................................................................. 30
Appendix 1. Method validation and verification decision tree ...................................................................... 31
Amendments ................................................................................................................................................ 32
