Current perspectives on stability of protein drug products during formulation, fill and finish operations
Current perspectives on stability of protein drug products during formulation, fill and finish operations
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DOI：
10.1021/bp070462h
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发表时间：
2008-05-01
影响因子：
2.9
通讯作者：
Rajan, Rahul S.
中科院分区：
文献类型：
--
作者：
Rathore, Nitin;Rajan, Rahul S.
基于蛋白质的治疗方法的商业化是一项具有挑战性的任务，部分原因是在整个药品开发过程、储存、运输和患者给药过程中维持蛋白质溶液安全有效的困难。散装原料药经过一系列配制、填充和完成操作，以提供所需制剂和容器或递送装置中的最终剂型。在这些操作中的每一个期间的不同工艺参数可以影响最终产品的纯度、活性和功效。常见的蛋白质降解途径和各种物理和化学因素，可以诱导这种反应已经被广泛研究了多年。本综述概述了各种配制-灌装-成品操作，重点关注可能影响产品质量的工艺步骤和条件。已审查了各种生产操作，包括散装冻融、配制、过滤、灌装、冻干、检查、贴标、包装、储存、运输和交付。本文强调了我们目前对生物制药生产过程中蛋白质不稳定性问题的理解，并提供了有关工艺考虑的指导，有助于缓解这些问题。
Commercialization of protein-based therapeutics is a challenging task in part due to the difficulties in maintaining protein solutions safe and efficacious throughout the drug product development process, storage, transportation and patient administration. Bulk drug substance goes through a series of formulation, fill and finish operations to provide the final dosage form in the desired formulation and container or delivery device. Different process parameters during each of these operations can affect the purity, activity and efficacy of the final product. Common protein degradation pathways and the various physical and chemical factors that can induce such reactions have been extensively studied for years. This review presents an overview of the various formulation-fill-finish operations with a focus on processing steps and conditions that can impact product quality. Various manufacturing operations including bulk freeze-thaw, formulation, filtration, filling, lyophilization, inspection, labeling, packaging, storage, transport and delivery have been reviewed. The article highlights our present day understanding of protein instability issues during biopharmaceutical manufacturing and provides guidance on process considerations that can help alleviate these concerns.