Process & Product Development, Amgen Inc., Seattle, Washington 98119, USA.
J Pharm Sci. 2011 Dec;100(12):5126-41. doi: 10.1002/jps.22712. Epub 2011 Jul 24.
Design of experiment and statistical analyses were applied to evaluate the effects of several formulation components on the thermal and colloidal stability for a series of monoclonal antibody (mAb) formulations. The high-throughput assessment of the protein stability was performed by measuring the temperature of hydrophobic exposure (T(h) , thermal stability) and the diffusion interaction parameter (k(D) , colloidal stability). To correlate the measured parameters with protein stability, the propensity to aggregate was tested by exposing the mAb samples to two types of stress: mechanical stress caused by shaking agitation and thermal stress. Mechanical stress led to increased formation of large particles, whereas temperature stress resulted in an increase in oligomers. The data obtained from the stress studies were used to determine the critical values for the stability parameters. The optimal formulation compositions were determined based on the statistical models and the predication tests. This approach of high-throughput thermal and colloidal stability screening can be applied to the characterization and prediction of protein formulation properties.
实验设计和统计分析被应用于评估一系列单克隆抗体（mAb）制剂的多种配方成分对热和胶体稳定性的影响。通过测量疏水性暴露温度（T(h)，热稳定性）和扩散相互作用参数（k(D)，胶体稳定性），实现对蛋白质稳定性的高通量评估。为了将测量参数与蛋白质稳定性相关联，通过使 mAb 样品经受两种类型的应激（由摇动搅拌引起的机械应激和热应激）来测试聚集倾向。机械应激导致大颗粒的形成增加，而温度应激导致低聚物增加。从应激研究中获得的数据用于确定稳定性参数的临界值。基于统计模型和预测测试确定了最佳配方组成。这种高通量热和胶体稳定性筛选方法可应用于蛋白质配方特性的表征和预测。
