Protocol, method validation concentration levels

If analytical methods are validated in inter-laboratory validation studies, documentation should follow the requirements of the harmonized protocol of lUPAC. " However, multi-matrix/multi-residue methods are applicable to hundreds of pesticides in dozens of commodities and have to be validated at several concentration levels. Any complete documentation of validation results is impossible in that case. Some performance characteristics, e.g., the specificity of analyte detection, an appropriate calibration range and sufficient detection sensitivity, are prerequisites for the determination of acceptable trueness and precision and their publication is less important. The LOD and LOQ depend on special instmmentation, analysts involved, time, batches of chemicals, etc., and cannot easily be reproduced. Therefore, these characteristics are less important. A practical, frequently applied alternative is the publication only of trueness (most often in terms of recovery) and precision for each analyte at each level. No consensus seems to exist as to whether these analyte-parameter sets should be documented, e.g., separately for each commodity or accumulated for all experiments done with the same analyte. In the latter case, the applicability of methods with regard to commodities can be documented in separate tables without performance characteristics. 

The ISO definition of validation is confirmation by examination and provision of objective evidence that the particular requirements of a specified intended use are fulfilled [15]. Method validation is needed to confirm the fitness for purpose of a particular analytical method, that is, to demonstrate that a defined method protocol, applicable to a specified type of test material and to a defined concentration rate of the analyte —the whole is called the analytical system — is fit for a particular analytical purpose [4]. This analytical purpose reflects the achievement of analytical results with an acceptable standard of accuracy. An analytical result must always be accompanied by an uncertainty statement, which determines the interpretation of the result (Figure 6). In other words, the interpretation and use of any measurement fully depend on the uncertainty (at a stated level of confidence) associated with it [8]. Validation is thus the tool used to demonstrate that a specific analytical method actually measures what it is intended to measure and thus is suitable for its intended purpose [11,55,56]. 

Two landmark articles published by H. Mark et al. and G. E. Ritchie et al. [30, 31] demonstrate how ICH Q2 principles can be applied when developing a near-infrared method. The first part of the series describes the method validation concepts as described in this section and proposes additional validation protocols. The second part focuses on the implementation of assay and content uniformity methods for solid dosage forms. Authors present at length how each criterion was validated and how they meet ICH and FDA requirements. For instance, repeatability was tested with the predictions of 13 repeats of tablets at three different concentration levels (80,100, and 120% w/w). In addition to the stated guidelines, authors used ASTM E1655-97 [12] to provide statistics analysis that is not directly provided in ICH Q2(R1). 

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