Viral clearance capacity by continuous Protein A chromatography step using Sequential MultiColumn Chromatography

Mimicking continuous capture chromatography for virus clearance using a single chromatography column model

“…[ 7,15–17 ] This also corroborates the validity of our approach, spiking virus into spent load before loading onto column 2, as spent load of column 1 would majorly contain virus flowing through column 1. [ 2 ]…”

“…Continuous chromatography has increasingly been used for clinical manufacturing, due to economic benefits, reduced resin and buffer needs, and fewer waste amounts. [ 1,2 ] Different vendors have developed and provide continuous chromatography systems, for example, Chromacon, Novasep, Sartorius, Cytiva, Lewa, and others. These can be run in simulated moving bed principle, for example, the BioSMB system, or periodic counter‐current mode, for example, Cytiva systems.…”

“…Additionally, resin utilization and number of cycles per column are improved especially for clinical manufacturing. [ 2,5,6 ] As protein A resin is one of the most expensive resins for biologics manufacturing, focus of continuous chromatography is currently with the protein A capture step, leveraging the maximum of economic benefits. [ 2 ] The protein A step is robust with regards to impurity removal such as host cell proteins, but only contributive towards virus clearance of the overall downstream process.…”

“…[ 2,5,6 ] As protein A resin is one of the most expensive resins for biologics manufacturing, focus of continuous chromatography is currently with the protein A capture step, leveraging the maximum of economic benefits. [ 2 ] The protein A step is robust with regards to impurity removal such as host cell proteins, but only contributive towards virus clearance of the overall downstream process. [ 7 ] Yet, for commercial manufacturing typically also the protein A step is included in virus clearance studies besides polishing chromatography steps.…”

The rise of continuous flow biocatalysis – fundamentals, very recent developments and future perspectives

“…Therefore, a continuous flow operation improves a greater number of purification cycles within a smaller column while utilizing shorter process times, which is a major advantage when purifying less stable proteins. 233 Generally, in situ solid phase adsorption can be used for continuous flow biocatalysis. Although various adsorption materials are now moderately used in the literature (see entry 1, 5 and 7 in Table 2), a systematic screening of the large number of commercially available adsorber materials (and ion exchange resins) is still lacking in the research field.…”