Dowd Christopher J
Genentech, Inc., South San Francisco, California 94080, USA.
Biotechnol Bioeng. 2009 Jun 15;103(3):574-81. doi: 10.1002/bit.22275.
Virus filtration is becoming increasingly prominent in biopharmaceutical recovery processes as a robust method to remove a broad range of virus types. Increasing batch sizes will require large numbers of individual virus filter elements operating in parallel. Before adopting a more complex strategy for managing the integrity testing of large assemblies of virus filters, it is important to understand the sensitivity of the forward flow diffusion test for a single filter and for multiple filters in a single housing. An approach has been developed to estimate the largest hole that could consistently go undetected in a single filter within a larger assembly of virus filters. The integrity test limited minimum log reduction value (LRV) is determined based on the size of the hole as a function of the number of filters in the housing. This minimum LRV is shown to be largely insensitive to the number of filters within the housing. The likelihood of such damage occurring is expected to be very low. This analysis suggests there is minimal benefit to placing filters in individual housings or to adjusting the test specification to compensate for larger numbers of filters in a given housing.
在生物制药回收过程中，病毒过滤作为一种去除多种病毒类型的可靠方法正变得越来越重要。批次规模的不断扩大将需要大量单个病毒过滤元件并行运行。在采用更复杂的策略来管理大型病毒过滤器组件的完整性测试之前，了解正向流动扩散测试对单个过滤器以及单个外壳中多个过滤器的灵敏度非常重要。已开发出一种方法来估计在大型病毒过滤器组件中单个过滤器内可能始终未被检测到的最大孔径。完整性测试的有限最小对数减少值（LRV）是根据孔径大小作为外壳中过滤器数量的函数来确定的。结果表明，该最小LRV在很大程度上对外壳内过滤器的数量不敏感。预计发生这种损坏的可能性非常低。该分析表明，将过滤器放置在单个外壳中或调整测试规格以补偿给定外壳中更多数量的过滤器几乎没有益处。
