Meeting Report—Workshop on Virus Removal by Filtration: Trends and New Developments
Meeting Report—Workshop on Virus Removal by Filtration: Trends and New Developments
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会议报告——过滤去除病毒研讨会：趋势和新进展
DOI：
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发表时间：
2013
影响因子：
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通讯作者：
S. Ruiz
中科院分区：
文献类型：
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作者：
H. Willkommen;J. Blümel;K. Brorson;Dayue Chen;Qi Chen;A. Gröner;T. Kreil;J. Robertson;Michel Ruffing;S. Ruiz
研讨会于2011年6月27日在巴塞罗那举行，同时举行了2011年PDA病毒和TSE(传染性海绵状脑病)安全论坛。抗病毒过滤器是保证生物医药产品高病毒安全水平的重要工具。研讨会讨论了重要参数，如病毒尖峰制剂的特性、不同品牌过滤器的病毒滞留机理、使用预过滤器来改善过滤性能，以及为特定产品选择最合适的过滤器的策略。来自全球不同地区的发言者和监管者参加了研讨会结束时的小组讨论，得出以下结论：病毒滞留的主要机制是大小排斥；然而，过滤是复杂的，蛋白质和病毒可以以多种方式与膜相互作用。过滤过程中的压力中断导致病毒通过增强。小鼠白血病病毒(MuLV)通过细小病毒过滤器的报道从未见过。一个小病毒可以被用来声称是像MuLV这样的大病毒，这是有道理的。这依赖于这样的假设，即模型细小病毒与蛋白质之间不存在聚集或相互作用，从而产生比逆转录病毒更大的聚集。为了在大规模生产中提高过滤的流量和吞吐量，正在研究几种预滤器。讨论了预滤器和病毒保持滤器是否可以被视为一个单位的操作，以便两者的病毒保留可以被称为这一制造步骤的病毒清除能力。这个问题引起了一些争议：一些人认为这种组合正确地反映了生产条件，而另一些人则讨论了病毒滞留的不同机制，这些机制需要单独研究。总之，研讨会被视为监管机构和行业之间讨论的一个宝贵论坛；有人建议，如果可能，应在下一届PDA病毒和TSE安全会议上再次提供此类论坛。研讨会摘要：研讨会于2011年6月27日在巴塞罗那举行，同时举行了2011年PDA病毒和TSE(传染性海绵状脑病)安全论坛。抗病毒过滤器是保证生物医药产品高病毒安全水平的重要工具。研讨会讨论了重要参数，如病毒尖峰制剂的特性、不同品牌过滤器的病毒滞留机理、使用预过滤器来改善过滤性能，以及为特定产品选择最合适的过滤器的策略。在研讨会结束时，讨论的几个方面总结如下：病毒保留的主要机制是大小排斥，但相互作用是复杂的。过滤过程中的压力中断导致病毒通过增强。小鼠白血病病毒(MuLV)通过细小病毒过滤器的报道尚未见报道，因此微小病毒可能是MuLV这样的大病毒的代名词。一些小组成员认为预滤器和病毒保持过滤器的组合正确反映了生产条件；另一些小组成员讨论了病毒保留的不同机制，需要单独研究。总而言之，研讨会被视为监管机构和行业之间讨论的一个宝贵论坛。
The workshop was held on 27 June 2011 in Barcelona, in conjunction with the PDA Virus & TSE (transmissible spongiform encephalopathy) Safety Forum 2011. Virus-retentive filters are important tools to assure a high virus safety level of biological medicinal products. Important parameters such as properties of virus spike preparations, mechanism of virus retention by different filter brands, use of prefilters to improve the filtration performance, and, finally, strategies to select the most appropriate filter for a specific product were discussed on the workshop. The panel discussion at the end of the workshop that involved speakers and regulators from different global areas came to following conclusions: The major mechanism of virus retention is size exclusion; filtration, however, is complex and protein and virus can interact with the membrane in multiple ways. Pressure interruption during filtration resulted in enhanced virus passage. It has never been reported that murine leukemia virus (MuLV) passes a parvovirus filter. It makes sense that a small virus can be used to provide a claim for a large virus like MuLV. This relies on the assumption that there is no aggregation or interaction of the model parvovirus with proteins leading to aggregates larger than retroviruses. Several prefilters are under investigation to improve flow rate and throughput of filtration in large-scale manufacture. It was discussed whether the prefilter and the virus-retentive filter can be viewed as one unit operation so that virus retention by both can be claimed as the viral clearance capacity of this manufacturing step. This question engendered some controversy: whereas some saw the combination as a correct reflection of manufacturing conditions, others discussed the different mechanisms of virus retention, which need to be studied separately. All together, the workshop was seen as a valuable forum for the discussion between regulators and industry; it was proposed that such forum should be provided again if possible in connection with one of the next PDA Virus & TSE Safety Conferences. LAY ABSTRACT: The workshop was held on 27 June 2011 in Barcelona, in conjunction with the PDA Virus & TSE (transmissible spongiform encephalopathy) Safety Forum 2011. Virus-retentive filters are important tools to assure a high virus safety level of biological medicinal products. Important parameters such as properties of virus spike preparations, mechanism of virus retention by different filter brands, use of prefilters to improve the filtration performance and, finally, strategies to select the most appropriate filter for a specific product were discussed on the workshop. At the end of the workshop, aspects of the discussion were summarized by the following: The major mechanism of virus retention is size exclusion, but interactions are complex. Pressure interruption during filtration resulted in enhanced virus passage. It has never been reported that murine leukemia virus (MuLV) passes a parvovirus filter, and thus the parvovirus may provide a claim for a large virus like MuLV. Combination of prefilter and the virus-retentive filter are seen by some panelists as a correct reflection of manufacturing conditions; others discussed the different mechanisms of virus retention, which need to be studied separately. All together, the workshop was seen as a valuable forum for the discussion between regulators and industry.