Tangential flow filtration (TFF) is used in the biotechnology industry for concentrating the therapeutic proteins and exchanging it into the final formulation buffer to produce bulk drug substance (BDS). Traditionally, TFF is optimized based on a target processing time and protein concentrations while TFF cassettes are generally chosen on the basis of vendor recommendations and company-specific process platforms. Detrimental changes to the BDS quality often result from changes in TFF process parameters such as crossflow velocity and concentration, but the effects of the type of cassette screened channel have not been fully evaluated. This work examined the role of TFF cassette channel shear on the process performance (hydraulic) and on the quality of the BDS. Shear stress models of screened channels incorporating different screens were developed in this work. The effect of protein solubility as a function of concentration and buffer composition was examined and used to support the hydraulic data, as well as to provide insight into the effects of process buffers on the protein during the buffer exchange process. Experimental results were obtained using shear sensitive/insensitive monoclonal antibodies and fusion proteins as a function of protein concentration for different screened channels. These results were compared to theoretical findings. BDS quality was evaluated using various analytical techniques as a function of protein concentration, buffer composition, crossflow velocity and membrane screens, and an optimal window of operation for the TFF process was identified.

Impact of channel shear effects on process hydraulics and biologics quality during ultrafiltration and diafiltration (UF/DF)

251st National Meeting (2016)

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