(233ax) 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.