Abstract
The impact of two different quality feeds, derived using two different harvest clarification processes, on protein A periodic counter‐current chromatography (PCC) design and performance is investigated. Data from batch experiments were input into a model to design optimal PCC operating parameters specific to each feed material. The two clarification methods were: depth filtration using a wetlaid matrix which has Q‐functionality; and a combination of depth filtration and chromatographic clarification, using a Q‐functional nonwoven with a high anion exchange capacity (Emphaze™ AEX Hybrid Purifier) in which key impurities such as host cell DNA (HCDNA) and host cell proteins (HCP) are removed. The model predicted 34% better productivity for the chromatographically clarified cell culture fluid (CCCF) using a 4 column system, and productivity gains of 28% using only 3 columns enabling the option to simplify the protein A PCC strategy. Experimental validation of the predicted optimized PCC operating parameters using industrially relevant monoclonal antibody (mAb) CCCF feedstock over 100 cycles showed productivity gains of 49% for the chromatographically clarified material. HCP concentration was 11‐fold lower, and HCDNA concentration was reduced by 4.4 Log Reduction Value (LRV) in the protein A PCC eluates. This work, therefore, demonstrates that the removal of HCDNA and HCP during clarification is an effective strategy for improving protein A PCC performance. This was achieved using the Emphaze™ AEX Hybrid Purifier which can be easily incorporated into a batch or continuous process, in a scalable fashion, without adding additional separate unit operations. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1380–1392, 2018
Highlights
IntroductionA number of academic and commercial entities are currently exploring continuous processing for recombinant protein manufacturing.[4] adoption has been slow due to the lack of a regulatory precedent, the need for better online process analytics (PAT) to improve process control, the inertia due to existing capital equipment for batch processing, and the perceived complexity associated with continuous manufacturing.[3,5,6,7,8]
Continuous processing has the potential to bring many advantages to the production of biotherapeutics such as lower capital costs, due to the use of smaller equipment and storage vessels, higher productivity, lower buffer consumption, and the possibility of steady-state operation in some circumstances.[1,2,3]A number of academic and commercial entities are currently exploring continuous processing for recombinant protein manufacturing.[4]
There is no significant difference in the breakthrough behavior of FT-AEX clarified feed material compared to the depth filter clarified feed material, at higher residence times
Summary
A number of academic and commercial entities are currently exploring continuous processing for recombinant protein manufacturing.[4] adoption has been slow due to the lack of a regulatory precedent, the need for better online process analytics (PAT) to improve process control, the inertia due to existing capital equipment for batch processing, and the perceived complexity associated with continuous manufacturing.[3,5,6,7,8]. A significant amount of work has been done by different research groups on periodic counter-current chromatography (PCC), and several groups have demonstrated capacity utilization and productivity gains over batch systems in most cases.[9,10,11,12] There has been some work, using decisional tools, which demonstrates the economic benefits of inclusion of continuous capture chromatography as part of a hybrid approach for commercial production.[13] as with continuous processing in general, one of the barriers to implementation of continuous multicolumn chromatography is system complexity, when more than 4 columns are used.[14]
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