Process Innovation and Optimization of a Commercial Cell Culture Process

Reduction of cadence and optimization of process yield are both required to maximize commercial biopharma manufacturing plant output. Often, these are mutually exclusive and concessions must be made to one or both areas to improve overall plant efficiency or maintain product quality. This abstract describes innovative optimization approaches on two different mammalian cell culture unit operations to improve both cadence and yield.

In the first example, the mammalian cell culture process described requires control of inoculum expansion at a low final viable cell density target, above which viability drop and growth lag are observed in the subsequent stage. The inoculum expansion and seed bioreactor stages require a precise control of transfer conditions to maintain the culture within certain viable cell density range. A flexible and scalable inoculum expansion process with robust control has been implemented. The process is resilient and supports a wide variety of plant cadence targets. In the second example the mammalian cell culture process described showed no increase in final output when production bioreactor titer improved by 20%. Data driven analysis of the production process showed a negative correlation between production bioreactor titer and primary recovery step yield. Multi Variate Analysis (MVA) was performed to identify drivers for lower step yields and process optimization.