Robust scale-up of dead end filtration: Impact of filter fouling mechanisms and flow distribution
Robust scale-up of dead end filtration: Impact of filter fouling mechanisms and flow distribution
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DOI：
10.1002/bit.20587
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发表时间：
2005-11-05
影响因子：
3.8
通讯作者：
Pujar, NS
中科院分区：
文献类型：
--
作者：
Laska, ME;Brooks, RP;Pujar, NS
死端过滤步骤的稳健设计和生产规模下的所得性能依赖于使用小型过滤器单元收集的实验室数据。在工艺开发过程中，重要的是表征和了解工艺流的过滤器结垢机制，以便准确评估生产规模所需的过滤器面积。成功的放大还需要将实验室规模的过滤数据与对全尺寸过滤设备中的流动特性的理解相结合。介绍了一项关于第二代多糖疫苗生产工艺中使用的深层过滤步骤的开发和放大的案例研究。操作参数对过滤器性能的影响进行了实验，其特征在于一组不同的工艺流。当在低通量下操作时，过滤器容量显著降低，这是由低过滤压力和高流粘度引起的。通量对过滤器容量的影响可以通过过滤器结垢的单一机理模型来解释。为了补充实验室过滤数据，对生产规模过滤设备中的流体流动和分布特性进行了仔细评价。该分析确定了需要额外的放大系数来解释大型过滤器外壳中不均匀的过滤器面积使用。事实证明，这种理解对于最终设备设计和深层过滤步骤定义至关重要，从而在生产规模下实现了稳健的工艺性能。(c)2005 Wiley Periodicals，Inc.
Robust design of a dead end filtration step and the resulting performance at manufacturing scale relies on laboratory data collected with small filter units. During process development it is important to characterize and understand the filter fouling mechanisms of the process streams so that an accurate assessment can be made of the filter area required at manufacturing scale. Successful scale-up also requires integration of the lab-scale filtration data with an understanding of flow characteristics in the full-scale filtration equipment. A case study is presented on the development and scaleup of a depth filtration step used in a 2nd generation polysaccharide vaccine manufacturing process. The effect of operating parameters on filter performance was experimentally characterized for a diverse set of process streams. Filter capacity was significantly reduced when operating at low fluxes, caused by both low filtration pressure and high stream viscosity. The effect of flux on filter capacity could be explained for a variety of diverse streams by a single mechanistic model of filter fouling. To complement the laboratory filtration data, the fluid flow and distribution characteristics in manufacturing scale filtration equipment were carefully evaluated. This analysis identified the need for additional scale-up factors to account for non-uniform filter area usage in large-scale filter housings. This understanding proved critical to the final equipment design and depth filtration step definition, resulting in robust process performance at manufacturing scale. (c) 2005 Wiley Periodicals, Inc.