Bioassay Sciences & Development, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany;
Data and Statistical Sciences, AbbVie Inc., North Chicago, IL, USA.
PDA J Pharm Sci Technol. 2021 Mar-Apr;75(2):173-187. doi: 10.5731/pdajpst.2020.012096. Epub 2020 Sep 30.
Relative potency assays for biological therapeutics require statistical evaluation to demonstrate similarity between the dose-response curves of a reference standard and the test samples. We developed an equivalence testing approach that can be utilized for the complete potency assay life cycle, from early development until commercialization. This approach was based on the use of generic equivalence margins to enable equivalence testing at the beginning of assay development, when the body of assay-specific data is still very limited. Generic equivalence margins for equivalence testing of four-parameter logistic curve fits were established for bioassays and binding assays spanning a variety of designs, formats, and read-outs. We also established that equivalence testing using ratios of the reference standard and test sample was superior to equivalence testing using absolute differences. Based on a large body of historical data, generic equivalence margins were determined for the curve upper asymptote, slope, and dynamic range. Furthermore, we developed a road map to guide the implementation of generic or assay-specific margins to ensure the appropriate data analysis approach is being applied during the assay life cycle.
相对效力测定法用于生物治疗药物，需要进行统计学评价，以证明参比标准和测试样本的剂量-反应曲线之间具有相似性。我们开发了一种等效性检验方法，可用于完整的效力测定法生命周期，从早期开发到商业化。该方法基于使用通用等效性边界，以在测定开发的早期阶段进行等效性检验，此时测定特异性数据仍然非常有限。为了进行生物测定和结合测定的等效性检验，我们为四参数逻辑曲线拟合建立了通用等效性边界，这些测定涵盖了各种设计、格式和读数。我们还确定了使用参考标准和测试样本的比值进行等效性检验优于使用绝对差值进行等效性检验。基于大量的历史数据，我们确定了曲线上限、斜率和动态范围的通用等效性边界。此外，我们制定了路线图，以指导通用或测定特异性边界的实施，以确保在测定生命周期中应用适当的数据分析方法。
