There is growing interest in the development of fully integrated and continuous biomanufacturing processes that will not only enhance product quality and manufacturing flexibility but will also reduce the environmental impact of bioprocessing. This includes final formulation of biotherapeutics to remove small impurities and achieve the desired buffer conditions for protein storage and delivery. The objective of this study was to examine the performance of both a 3-stage continuous countercurrent diafiltration process and a continuous countercurrent dialysis process designed to achieve 99.9 % buffer exchange over a minimum of 24 hr.  Experimental data were obtained using human Immunoglobulin G as a model protein, with the protein exchanged from a phosphate to acetate buffer.  In addition, vitamin B12 removal was tracked as a model impurity. The staged diafiltration was performed using Pall Cadence™ Inline Concentrators which offer a high conversion in single pass operation, while he countercurrent dialysis was performed using Fresenius Optiflux dialyzers originally designed for hemodialysis.   <br/>Both systems showed 99.9% buffer exchange and impurity removal with continuous performance over 24 hr. The buffer usage for the countercurrent dialysis is less than 0.02 L/g at a protein concentration of 120 g/L, which is several-fold smaller than hat required in current batch diafiltration process. In addition, the cost of the hollow fiber dialyzers is more than 10-fold less than that for the diafiltration systems.  The lowest cost for the countercurrent staged diafiltration is a function of the buffer and module cost, with the 3-stage system typically providing the optimal performance.  These results provide important insights into the development of continuous membrane processes for protein formulation and buffer exchange.

Continuous formulation / buffer exchange using staged diafiltration or countercurrent dialysis

2019 Spring National Meeting

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