Each process step in the manufacture of biological products requires expensive resources and reduces total process productivity. Since downstream processing of biologicals is the main cost driver, process intensification is a persistent topic during the entire product life cycle. We present here one approach for the intensification of bioprocesses by applying on-column virus inactivation using solvent/detergent (S/D) treatment during ion-exchange chromatography. The established purification process of a recombinant protein was used as a model to compare key process parameters (i.e., product yield, specific activity, impurity clearance) of the novel approach to the standard process protocol. Additional wash and incubation steps with and without S/D-containing buffers were introduced to ensure sufficient contact time to effectively eliminate enveloped viruses and to significantly decrease the amount of S/D reagents. Comparison of key process parameters demonstrated equivalent process performance. To assess the viral clearance capacity of the novel approach, XMuLV was spiked as model virus to the chromatographic load and all resulting fractions were analyzed by TCID₅₀ and RT-qPCR. Data indicates the inactivation capability of on-column virus inactivation even at 10% of the nominal S/D concentration, although the mechanism of viral clearance needs further investigation.

生物制品制造中的每个工艺步骤都需要昂贵的资源，并降低了总工艺生产率。由于生物制品的下游加工是主要的成本驱动因素，因此工艺强化是整个产品生命周期中持续存在的话题。我们在此提出一种强化生物过程的方法，即在离子交换色谱过程中使用溶剂/去污剂 (S/D) 处理进行柱上病毒灭活。使用已建立的重组蛋白纯化工艺作为模型来比较新方法与标准工艺方案的关键工艺参数（即产物产量、比活性、杂质清除率）。引入了使用和不使用包含 S/D 的缓冲液的额外洗涤和孵育步骤，以确保足够的接触时间，以有效消除包膜病毒并显着减少 S/D 试剂的量。关键工艺参数的比较证明了相同的工艺性能。_{为了评估新方法的病毒清除能力，将 XMuLV 作为模型病毒添加到色谱负载中，并通过 TCID 50}和 RT-qPCR分析所有所得级分。数据表明，即使在标称 S/D 浓度的 10% 下，柱上病毒也具有灭活能力，但病毒清除机制还需要进一步研究。