集成的连续生物处理已被确定为生物制药制造发展的下一个重要阶段。正在开发实现连续处理的多平台技术。多柱逆流色谱是该方向上的一个步骤,以提供提高的生产率和容量利用率,以捕获反应器收获物中存在的生物分子如单克隆抗体(mAb)并除去杂质。两种流行的多柱设计的基于模型的优化,对进料中不同浓度的mAb进行3柱和4柱定期逆流色谱(PCC),就地清洁和平衡方案的持续时间。包括三个性能指标的多目标优化问题,即,产品产量,生产力,并利用径向基函数优化技术求解产能利用率。加载过程中的表观速度,wash,和洗脱操作,以及多列操作中存在的不同阶段的持续时间被视为决策变量。不受洗涤体积数限制的优化结果表明,3-塔PCC的性能优于4-塔PCC。例如,在1.2mg/mL的饲料浓度下,生产力,产量和产能利用率,分别,为0.024mg/mL。s,对于3-柱PCC和0.017mg/mL为0.94和0.94。s,0.87,4列PCC为0.83。在较高的进料浓度下也观察到类似的趋势。然而,当包括对洗涤体积数量的约束时,发现4-塔PCC在不同的操作条件下产生一致的生产率和产物产率,但是以降低的容量利用率为代价。
Integrated continuous bioprocessing has been identified as the next important phase of evolution in biopharmaceutical manufacturing. Multiple platform technologies to enable continuous processing are being developed. Multi-column counter-current chromatography is a step in this direction to provide increased productivity and capacity utilization to capture biomolecules like monoclonal antibodies (mAbs) present in the reactor harvest and remove impurities. Model-based optimization of two prevalent multi-column designs, 3-column and 4-column periodic counter-current chromatography (PCC) was carried out for different concentrations of mAbs in the feed, durations of cleaning-in-place and equilibration protocols. The multi-objective optimization problem comprising three performance measures, namely, product yield, productivity, and capacity utilization was solved using the Radial basis function optimization technique. The superficial velocities during load, wash, and elute operations, along with durations of distinct stages present in the multi-column operations were considered as decision variables. Optimization results without the constraint on number of wash volumes showed that 3-Column PCC performs better than 4-Column PCC. For example, at a feed concentration of 1.2 mg/mL, productivity, yield and capacity utilization, respectively, were 0.024 mg/mL.s, 0.94, and 0.94 for 3-Column PCC and 0.017 mg/mL.s, 0.87, and 0.83 for 4-column PCC. Similar trends were observed at higher feed concentrations also. However, when the constraint on number of wash volumes is included, 4-Column PCC was found to result in consistent productivity and product yield under different operating conditions but at the expense of reduced capacity utilization.