Gilead Alberta ULC, 1021 Hayter Road NW, Edmonton, AB T6S 1A1, Canada.
Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA.
J Pharm Biomed Anal. 2024 Oct 15;249:116344. doi: 10.1016/j.jpba.2024.116344. Epub 2024 Jul 9.
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.
分析测试方法的性能至关重要，以确保影响药物产品疗效和质量的决策基于准确和可靠的结果。如 USP<1220> 所述，并在 ICH Q14 中倡导，持续验证与偏差和精密度相关的关键方法属性对于确保分析测试方法整个生命周期内的方法性能至关重要。随着制药行业中分析方法的持续验证计划的成熟，需要额外的监测工具来提供强大且具有成本效益的验证计划。本文提出了一种新的方法，可直接从常规方法执行过程中生成的结果评估分析方法的变异性。本文展示了该方法在利用单点外部参考校准的小分子液相色谱测定方法中的实施情况。描述了减少所需收集数据的方法，并拓宽该方法的适用性，以适用于广泛的分析方法。最后，讨论了该方法在方法开发活动中的应用，以帮助确定变异性来源，并有效地选择复制策略，从而在整个方法生命周期内全面了解方法的变异性。
