A practical approach to estimate analytical method variability from routine testing.

ABSTRACT

The performance of analytical test methods is critical to ensure decisions that affect efficacy and quality of pharmaceutical products are based on accurate and reliable results. As described in USP <1220> and advocated for in ICH Q14, continued verification of critical method attributes linked to bias and precision is essential to ensure method performance throughout the lifecycle of an analytical test method. As continued verification programs for analytical methods within the pharmaceutical industry mature, additional monitoring tools are required to deliver robust and cost-effective verification programs. Herein, a novel methodology is presented to evaluated analytical method variability directly from results generated during routine method execution. The implementation of the methodology is demonstrated for a small molecule liquid chromatographic assay method utilizing a single-point external reference calibration. Approaches to reduce the required data to be collected and broaden the applicability of the methodology to a wide range of analytical methods is described. Finally, the application of the methodology to method development activities is discussed to aid in the identification of variability sources and effectively select replication strategies, thus allowing a holistic understanding of method variability throughout the entirety of the method lifecycle.