Li Xuanwen, Wang Fengqiang, Li Hong, Richardson Douglas D, Roush David J
Analytical Research & Development, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Biologics Process Research & Development, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Antib Ther. 2022 Jan 15;5(1):42-54. doi: 10.1093/abt/tbac002. eCollection 2022 Jan.
Nonionic surfactant polysorbates, including PS-80 and PS-20, are commonly used in the formulation of biotherapeutic products for both preventing surface adsorption and acting as stabilizer against protein aggregation. Trace levels of residual host cell proteins (HCPs) with lipase or esterase enzymatic activity have been shown to degrade polysorbates in biologics formulation. The measurement and control of these low abundance, high-risk HCPs for polysorbate degradation are an industry-wide challenge to achieve desired shelf life of biopharmaceuticals in liquid formulation, especially for high-concentration formulation product development. Here, we reviewed the challenges, recent advances, and future opportunities of analytical method development, risk assessment, and control strategies for polysorbate degradation during formulation development with a focus on enzymatic degradation. Continued efforts to advance our understanding of polysorbate degradation in biologics formulation will help develop high-quality medicines for patients.
非离子表面活性剂聚山梨酯，包括PS - 80和PS - 20，常用于生物治疗产品的配方中，既用于防止表面吸附，又作为抗蛋白质聚集的稳定剂。已表明具有脂肪酶或酯酶活性的痕量残留宿主细胞蛋白（HCPs）会在生物制品配方中降解聚山梨酯。对于聚山梨酯降解而言，测量和控制这些低丰度、高风险的HCPs是整个行业面临的挑战，以实现液体制剂中生物制药的期望保质期，特别是对于高浓度制剂产品的开发。在此，我们综述了在制剂开发过程中聚山梨酯降解的分析方法开发、风险评估和控制策略方面的挑战、最新进展以及未来机遇，重点关注酶促降解。持续努力加深我们对生物制品配方中聚山梨酯降解的理解将有助于为患者开发高质量的药物。
