Analytical Chemistry, Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Formulation Group, Regeneron Pharmaceuticals, Tarrytown, NY, USA.
MAbs. 2023 Jan-Dec;15(1):2232486. doi: 10.1080/19420862.2023.2232486.
Polysorbates (PSs) are a class of surfactants commonly used in the formulation of protein therapeutic agents to provide protection against denaturation and aggregation. When the PS in these drug formulations degrades, loss of stabilization of the protein therapeutic and formulation may occur, resulting in particulate formation or other undesirable changes in product critical quality attributes. Here, we present a simplified platform to predict long-term PS20 and PS80 degradation for monoclonal antibody drugs containing the PS-degrading enzyme lysosomal acid lipase. The platform was based on a temperature-dependent equation derived from existing PS20 degradation stability data. Accurate prediction of both PS20 and PS80 hydrolysis for as long as 2 years was achieved through short-term kinetics studies performed within 2 weeks. This platform substantially shortens the time required to determine the long-term stability of PS degradation and therefore can be used to guide the purification process and optimization of antibody formulations.
聚山梨酯（PS）是一类广泛用于蛋白质治疗药物制剂的表面活性剂，可提供对变性和聚集的保护。当这些药物制剂中的 PS 降解时，蛋白质治疗剂和制剂的稳定性可能会丧失，导致颗粒形成或产品关键质量属性的其他不良变化。在这里，我们提出了一个简化的平台，用于预测含有溶酶体酸性脂肪酶的 PS 降解酶的单克隆抗体药物的 PS20 和 PS80 的长期降解。该平台基于从现有 PS20 降解稳定性数据得出的温度依赖性方程。通过在 2 周内进行的短期动力学研究，实现了长达 2 年的 PS20 和 PS80 水解的准确预测。该平台大大缩短了确定 PS 降解长期稳定性所需的时间，因此可用于指导抗体制剂的纯化过程和优化。
