Continuous processes for the production of high value biological products have generated an increasing interest in the last years. These have shown potential to reduce cost and facility size while delivering improved quality and flexible multi-product manufacturing facilities [1]. Although there are still significant challenges in developing integrated continuous bioprocesses, recent technological advances have provided a number of attractive options for development of truly continuous bioprocessing operations. Continuous capture processes show several advantages compared to batch. Mainly improved specific productivity, reduced buffer consumption but the most important it opens the possibility of a streamlined connection with the upstream cell culture [2]. Among others, the twin-column CaptureSMB [3], the Sequential Multi-Column Chromatography (SMCC) [4] and the 3- or 4-column periodic counter-current chromatography (PCC) [2] have shown as promising processes for an efficient and robust integrated cell-culture setup. At Novartis we have implemented an adapted continuous capture chromatography process. A lean development approach was employed to define the main process characteristics based on the loading dynamics. Furthermore, a UV-based column loading control to accommodate fluctuations from both upstream and column performance was successfully employed. Here we will discuss the main challenges that arise from such an increased complexity process: why the current design? What’s the right column size? What are the main benefits and limitations? How to integrate with the continuous cell-culture? A general overview will be given and ultimately show how it can look on a future commercial scale manufacturing plant. REFERENCES [1] Zydney, AL, Continuous downstream processing for high value biological products: A Review, BIOTECHNOLOGY AND BIOENGINEERING, 113 (465-475); [2] Warikoo, V., et.al., Integrated Continuous Production of Recombinant Therapeutic Proteins, BIOTECHNOLOGY AND BIOENGINEERING, 109(3018-3029); [3] Baur D, et.al., Comparison of batch and continuous multi-column protein A capture processes by optimal design, BIOTECHNOLOGY JOURNAL, 11(920-931); [4] Candy K.S., Ng, et.al., Design of high productivity sequential multi-column chromatography for antibody capture, FOOD AND BIOPRODUCTS PROCESSING, 92(233-241);

Integrated continuous protein A capture chromatography: Lean development approach

253rd National Meeting (2017)

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