Normal-flow virus filtration: detection and assessment of the endpoint in bioprocessing
Normal-flow virus filtration: detection and assessment of the endpoint in bioprocessing
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DOI：
10.1042/ba20050056
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发表时间：
2005-10-01
影响因子：
2.8
通讯作者：
Bailey, M
中科院分区：
文献类型：
--
作者：
Bolton, G;Cabatingan, M;Bailey, M
使用商业工艺流体和模型进料流研究了模型病毒噬菌体Phi X-174通过正常流量病毒过滤器的突破。结果表明：（i）PhiX-174是哺乳动物细小病毒[MMV]的合理模型（鼠细小病毒）];（ii）Phi X-174 LRV [log（减少值）]与各种条件下处理的体积相比，显示出与流量下降百分比更好的相关性;（iii）尽管病毒LRV的下降程度取决于过滤器结垢的机制，但病毒验证研究中的结垢机制代表了在实际生产条件下可能发现的结垢机制。提出了许多工艺流导致LRV下降的机理是由于小孔的选择性堵塞。的理论模型以及预测方程LRV下降与流量衰减的推导，从过滤研究使用孔堵塞原料的实验结果与方程是一致的。由于蛋白质溶液在过滤过程中的吸附与堵塞行为可能会有所不同，因此可能需要在生物制药产品特定的基础上评价LRV与流量衰减的关系。
The breakthrough of a model virus, bacteriophage, Phi X-174, through normal-flow virus filters was studied using both commercial process fluids and model feedstreams. The results indicate that (i) Phi X-174 is a reasonable model for a mammalian parvovirus [MMV (murine minute virus)] in virus filtration studies; (ii) Phi X-174 LRV [log (reduction value)] shows a better correlation with percentage flow decline compared with volume processed under a variety of conditions; (iii) although the extent of decline in virus LRV is dependent on the mechanism of filter fouling, the fouling mechanisms operative in a viral validation study are representative of those likely to be found under actual production conditions. The mechanism of LRV decline by many process streams was proposed to be due to selective plugging of small pores. A theoretical model as well as a predictive equation for LRV decline versus flow decay was derived; experimental results from filtration studies using pore-plugging feedstocks were consistent with the equation. As protein solutions may vary in their adsorptive versus plugging behaviour during filtration, an evaluation of the LRV-versus-flow-decay relationship on a biopharmaceutical-product-specific basis may be warranted.