Alternate Case 3: Single-Stage Batch Operation (Simple Induction)
The expression phase is initiated by sugar starvation, which is achieved using gravity sedimentation-assisted medium exchange. A simple induction method would be let the sugar deplete naturally – to tune the culture sugar concentration such that the time to depletion is set to coincide with desired final cell concentration. This is referred to as single-stage induction since a medium exchange operation is not required. Preliminary data suggests that this method has the potential to yield comparable growth and expression kinetics, but that the culture is slow to recover in semicontinuous operation (unpublished data). The batch mode operation models were adapted to the simple induction procedure by eliminating the medium exchange operation from sucrose-rich growth medium to sucrose-free medium and reducing sucrose concentration in the production bioreactor growth media by one-half of the base case growth medium.
COGS and CAPEX of the single-stage batch cases are listed in Table 3. These results correspond to a 3-6% reduction in COGS over the two-stage batch mode operation.
To better understand the economic impact of the two-stage (medium exchange) and single-stage (simple) induction methods, we performed a sensitivity analysis of the COGS to the cost of culture medium . The culture medium used in this study is inexpensive ($0.10/L growth medium; $0.09/L growth medium (half-sucrose); $0.11/L production medium). The costs, while calculated based on bulk price estimates of the raw material components, are comparable to a previously published analysis on cost-optimized plant cell culture media (Häkkinen et al., 2018). Other sources of culture medium for eukaryotic cell culture in batch mode operation cite $5-10/L (Harrison, Todd, Rudge, & Petrides, 2015; Kelley, 2009; Xu, Gavin, Jiang, & Chen, 2017).
The results of the analysis for a new facility including depreciation costs are shown in Figure 7. COGS increases linearly with culture medium cost in the two-stage and single-stage scenarios but at different rates proportional to culture medium requirements. There is a 6% reduction in COGS using single-stage batch operation when media costs are neglected, which increases to a 23% reduction in COGS at a scenario of $10/L culture medium.