High-productivity cell culture processes may be required to support potential high-dose blockbuster product(s). Even though it has been reported previously, most of the studies were performed at bench and pilot scales. There are limited reports of high-productivity processes at large scale manufacturing (&gt; 10,000-L).<br/><br/>In this presentation, we share a case study in which we were able to improve volumetric productivity of a cell culture process at 17,000-L scale by 50% through 1) implementing perfusion technology at the N-1 stage, 2) medium optimization, and 3) an adaptive feeding strategy. Specifically, we developed an in-house TFF perfusion system for pilot and large scale N-1 bioreactors. Both a hollow fiber and an open channel technology were evaluated and compared. Subsequently, medium components were re-balanced to adjust for changes in nutrient requirements with higher densities coming from the N-1 culture. The feed volume was also adjusted on a per cell basis based on biomass measurements using on-line capacitance probes. We will also share how we resolved engineering challenges encountered during scale-up and implementation of this intensified process using a new sparger design and an adaptive agitation strategy to accommodate high feed percentages. Finally, we will present manufacturing data and experience at the 17,000-L scale using this high-productivity process (750 mg/L/day).

Development of a high-productivity cell culture process and implementation at large scale

251st National Meeting (2016)

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