When two therapeutic agents are combined in a single formulation, i.e., coformulated, the quality and safety of the individual agents must be preserved. Here we describe an approach to evaluate the quality attributes of two individual monoclonal antibodies (mAbs), designated mAb-A and mAb-B, in coformulation. The mAbs were fractionated from heat-stressed coformulated drug product (DP) by hydrophobic interaction chromatography. Each purified mAb fraction was then compared with mAb-A and mAb-B in their individual formulations from the same drug substance sources used to make the coformulated DP lot, which was subjected to the same stress conditions. Product variants were evaluated and compared by using several analytical tests, including high-performance size exclusion chromatography (HPSEC), reducing and nonreducing gel electrophoresis, ion-exchange chromatography, capillary isoelectric focusing, and peptide mapping with mass spectrometry. Intermolecular interactions in coformulated and photostressed DPs were studied by evaluating aggregates fractionated from coformulated DP by HPSEC. Aggregate fractions of coformulated DP contained dimers, but not coaggregates, of mAb-A or mAb-B. Moreover, extensive assays for higher-order structure and biological interactions confirmed that there was no interaction between the two mAb molecules in the coformulation. These results demonstrate that the two coformulated therapeutic mAbs had the same quality attributes as the individually formulated mAb-A and mAb-B, no new quality attributes were formed, and no physicochemical, intermolecular, or biological interactions occurred between the two components. The approach described here can be used to monitor the product quality of other coformulated antibodies.

中文翻译：

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共配制抗体作为联合疗法的分析表征。

当将两种治疗剂组合在单一制剂中，即共同配制时，必须保持各个治疗剂的质量和安全性。在这里，我们描述了一种在联合配方中评估两个单独的单克隆抗体（mAb）（称为mAb-A和mAb-B）的质量属性的方法。通过疏水相互作用色谱法从热应激的共同配制的药物产品（DP）中分离出mAb。然后将每个纯化的mAb馏分与来自相同药物原料的mAb-A和mAb-B在其各自的配方中进行比较，这些原料用于制备共同配制的DP批次，并经受相同的压力条件。使用多种分析测试对产品变体进行评估和比较，包括高性能尺寸排阻色谱（HPSEC），还原和非还原凝胶电泳，离子交换色谱，毛细管等电聚焦和质谱分析肽图。通过评估HPSEC从共配制的DP中分离出的聚集体，研究了共配制的和光应力DP中的分子间相互作用。共配制的DP的聚集级分包含mAb-A或mAb-B的二聚体，但没有聚集体。此外，对高阶结构和生物学相互作用的广泛分析证实，在共制剂中两个mAb分子之间没有相互作用。这些结果表明，两种共同配制的治疗性mAb与单独配制的mAb-A和mAb-B具有相同的质量属性，没有形成新的质量属性，并且两种组分之间未发生任何物理化学，分子间或生物学相互作用。