Corteva Agriscience, 9330 Zionsville Rd, Indianapolis, 46268, Indiana, USA.
Bristol Myers Squibb, 556 Morris Ave., Summit, New Jersey, 07901, USA.
AAPS PharmSciTech. 2021 Jan 6;22(1):32. doi: 10.1208/s12249-020-01881-z.
The use of an aqueous-based surrogate solution in at-scale process development for biopharmaceutical drug products enables significant reduction in the usage of costly drug substance and improves confidence in initial drug product production runs performed using active biotherapeutic. Strategies for the formulation design of a surrogate solution that is representative of the unit operations in a typical drug product manufacturing process for a biopharmaceutical are presented herein, and a case study for the development of a surrogate solution for an example protein drug product is discussed. The surrogate was shown to have similar physical attributes to the drug product, including viscosity, surface tension, and density. The surrogate was used in at-scale process development of compounding, filling, and lyophilization operations in a single technical run, and the performance was shown to be similar to that of the drug product solution, providing a cost-effective and readily available option for process development while minimizing operator exposure to potentially hazardous drug solution and limiting drug wastage.
在生物制药产品的大规模工艺开发中使用基于水的替代溶液可显著减少昂贵药物成分的使用，并提高使用活性生物治疗药物进行初始药物产品生产的信心。本文介绍了用于代表典型生物制药药物产品制造过程中的单元操作的替代溶液的配方设计策略，并讨论了用于示例蛋白质药物产品的替代溶液的开发案例研究。结果表明，替代溶液具有与药物产品相似的物理属性，包括粘度、表面张力和密度。替代溶液在单一技术运行中用于化合物、填充和冷冻干燥操作的大规模工艺开发中，其性能与药物产品溶液相似，为工艺开发提供了一种具有成本效益且易于获得的选择，同时最大限度地减少了操作人员接触潜在危险药物溶液的机会并限制了药物浪费。
