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is slow to recover in semicontinuous operation (unpublished data).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.