COST MODEL RESULTS
Scenario 1: Base Case
The analysis in this scenario evaluates the process economics of the three production techniques using the assumptions stated
in the previous section. Figure 3 shows the total CoG per gram broken down into fixed capital charges and variable costs such
as materials, consumables, labor, and others (e.g., insurance, maintenance). As expected, the FB process has a higher upfront
capital burden ($53 million) due to the need for a longer seed fermentation train and larger overall fermentation volume.
The CFB and CP options benefit from increased throughput and reduced overall bioreactor capacity, which translates to lower
initial investment costs. The CFB and CP technologies offer substantial capital charge reductions of 13% and 32%, respectively,
relative to the FB process. The CoG per gram is inversely proportional to the annual product mass with the CP process producing
the most product (265 kg/year) and FB producing the least amount of product (130 kg/year). This correlation between low CoG
and high annual product mass is expected, because increased throughput of product will result in lower costs per gram produced.
Figure 3: Cost of goods (CoG) results for the base case. FB: fed-batch; CFB: concentrated fed-batch; CP: concentrated perfusion.
In the CP process, the materials costs contribute a significant amount to the CoG. This can be attributed to the intensive
usage of media over the extended perfusion culture cycle.
The model results indicate that the CP process (scenario 1c) is the most cost-effective technology with the lowest overall
CoG per gram of $87/g. The CFB process (scenario 1b) is slightly more expensive at $118/g. The FB process (scenario 1a) has
the highest CoG ($158/g). The CFB and CP options provide cost savings of about 25% and 45%, respectively, when compared to
the FB process.
Scenario 2: Changing the Titer for the CFB Process
The expression levels in the CFB process can vary depending on the type of cell line and duration of cell-line development.
In this section, the effect of changing the product titer for the CFB process is examined while keeping the bioreactor size
constant at 1,000 L (Figure 4). In the worst-case scenario, the titer is reduced from 17 g/L (scenario 1b) to 10 g/L (scenario
2a). In the best-case scenario, the titer is increased to 25 g/L (scenario 2b).
Figure 4. Cost of goods (CoG) results for the fed-batch (FB) process and the concentrated fed-batch (CFB) process at 10 g/L,
17 g/L, and 25 g/L (1,000 L bioreactor scale)
Reducing the titer, as expected, increases the CoG as the annual throughput is reduced. When the titer is reduced to 10 g/L
(scenario 2a), the CFB process appears less economical as the CoG ($184/g) is higher than the FB CoG at $158/g (scenario 1a),
as shown in Figure 4. On the other hand, when the titer is increased to 25 g/L, the CoG reduces to $87/g. This improvement
in the expression level would make the CFB process much more attractive than the FB process with significant cost savings
Scenario 3: Changing the Bioreactor Size for the CP Process
The bioreactor size used for running perfusion culture mode can vary. This section looks at changing the bioreactor size of
the CP process while keeping the titer unchanged at 0.8 g/L. Two other bioreactor sizes (500 L and 750 L) are considered in
this analysis. When the bioreactor volume is reduced to 500 L (scenario 3a in Figure 5), the CP process generates about the
same annual output (132 kg) as the FB process (130 kg). The CoG of the CP process increases from the base figure of $87/g
(scenario 1c) to $133/g (scenario 3a). The CP process at 500 L and 0.8 g/L is still more economical than the FB process. It
should be noted that the simplification of material and people flow provided by reduced bioreactor capacity in the CP facility
cannot be calculated easily but may provide the key driver to such technology being increasingly used in biomanufacturing.
Figure 5. Cost of goods (CoG) results for the fed-batch (FB) process and the concentrated fed-batch (CFB) process using 500
L, 750 L, and 1,000 L (0.8 g/L titer)