To provide expert guidance on the scope and scale of experiments required for single-laboratory method validation, enabling regulatory agencies to harmonize validation requirements.
This project will develop guidance on experimental designs suitable for determining method performance characteristics during single laboratory validation experiments. Where possible, the resulting report will include guidance on numerical values for such performance characteristics.
The output is intended to support implementation of the existing IUPAC Harmonized Protocol on Single-Laboratory Validation (PAC 2002, Vol. 74, No. 5, pp. 835-855), which specifies the performance characteristics to be assessed but currently includes no quantitative guidance on the scale of experimentation required.
It is currently envisaged that the guidance will be informed by statistical power considerations; that is, experimental requirements will be set so as to achieve a particular probability of correctly identifying significant adverse effects (such as a specified upper limit for bias). The guidance will indicate the power appropriate for different situations. For example, verification of performance of an established method, validation of a new method or validation of a new method intended for critical uses would attract increasingly stringent requirements. It is envisaged that the report will include example simple experiment designs and associated tables of replicate numbers for each such situation so that regulators can easily specify the level of stringency required and analysts can easily identify the scale of experimentation necessary to meet the requirement.
The requirements will be chosen so that they broadly reflect and harmonize current best practice.
The advantage of specifying requirements in terms of test power as well as listing specific experiments and experiment sizes is that it then becomes possible to permit any experiment design which is designed to achieve the necessary confidence. This provides for flexibility in specifying single-laboratory validation requirements, and allows analysts to design improved experiments which have greater efficiency while being able to demonstrate that the stringency is sufficient.
> project announcement published in Chem. Int. Nov-Dec 2009
May 2018 update – The project is progressing and a draft is now under revision.
Feb 2021 update – An advanced draft has been prepared and developed with the assistance of the working group. The draft covers the scale of experiments for three increasingly stringent levels of validation, labelled ‘verification’, ‘validation’ and ‘stringent validation’. The principle is that each is associated with a level of statistical power required of statistical tests used in declaring the analytical method fit for purpose. This provides a quantitative indication of the reliability, and hence number of replicates, required at each level. The levels have been chosen to align experiment sizes with typical recommendations in most regulated sectors. Flexibility in validation experiments is permitted via permission to use alternative experimental designs that provide the same test power and reliability; this allows laboratories or quality system developers to use alternative experimental design provided that the experiment is equally (or more) capable of detecting departures from specified requirements.
Page last updated 14 Apr 2021