Purification Process Development, Amgen Inc., Mail Stop 30W-2-A, One Amgen Center Dr., Thousand Oaks, California 91320, USA.
Biotechnol Bioeng. 2012 Dec;109(12):3084-92. doi: 10.1002/bit.24577. Epub 2012 Jun 27.
The demand for increased formulation concentrations for protein therapeutics puts a significant strain on already existing tangential flow filtration (TFF) systems that were constructed with lower protein concentration targets as part of their design criteria. TFF is commonly used to buffer exchange and concentrate the product to the appropriate drug substance concentration. Analyzing the ability of an existing TFF system to process under conditions outside its original design specifications can be challenging. In this analysis, we present a systematic approach to assess the operational limits of a TFF process with consideration of system performance parameters for changing process targets. In two new engineering diagrams, the recovery efficiency diagram and the operating space plot, all relevant operational constraints and parameters are related to allow rapid process fit evaluation. The engineering assessment of TFF systems presented in this article allows a rational review of system limitations during process fit evaluations of existing TFF systems. It also provides a rational basis for targeted system upgrades and setting system design specifications for the design of new systems if existing systems are found inadequate.
提高蛋白质治疗药物制剂浓度的需求给原本设计用于较低蛋白质浓度目标的现有切向流过滤（TFF）系统带来了巨大压力，这些系统是其设计标准的一部分。TFF 通常用于缓冲交换和将产品浓缩到适当的药物物质浓度。分析现有 TFF 系统在超出其原始设计规格的条件下进行处理的能力具有挑战性。在这项分析中，我们提出了一种系统方法来评估 TFF 工艺的操作极限，并考虑了改变工艺目标的系统性能参数。在两个新的工程图中，即回收率效率图和操作空间图中，将所有相关的操作限制和参数联系起来，以允许快速进行工艺拟合评估。本文中介绍的 TFF 系统工程评估允许在对现有 TFF 系统进行工艺拟合评估时对系统限制进行合理审查。如果发现现有系统不足，它还为有针对性的系统升级和为新系统设计系统设计规范提供了合理依据。
