Small-Molecule Pharmaceutical Impurities Test Method Validation: Precision Acceptance Criterion

This chapter presents a meaningful sample of AbbVie impurities and degradation products test method validation precision performance against the Horwitz Reproducibility acceptance criterion. The International Conference on Harmonization guideline for pharmaceutical small-molecule impurities test method validation does not provide any guidance in setting numerical validation performance criteria for linearity, accuracy, and precision. It specifies a numerical minimum acceptance criterion for signal-to-noise performance respective of the test method’s limit of detection and limit of quantitation. For the main component quantitation test method, sponsors could select to set absolutely the precision performance acceptance criterion as the tolerable variation predefined as a statistically based fraction of the active ingredient specification range. A specification-based approach to setting precision performance acceptance criterion for the active ingredient assay test method is sensible and straight forward from the scientific perspective and is less likely to be met with objection during regulatory review.