The cell density achieved in a CELLine bioreactor is typically 1 to 2 orders of magnitude higher than in a conventional culture
vessel, due to the optimized culture conditions described earlier. Consequently the product concentration also increases by
a factor in the range of 10 to 100. In the case of hybridomas, densities of 107 to 108 cells/mL and MAb concentrations between 1 and 2 mg/mL are achieved.1-4 The volume of supernatant produced with CELLine corresponds to the cell compartment volume (20 mL) where the secreted MAb
Another important parameter to consider is the duration of cultivation determining the number of times supernatant can be
harvested. Cells are cultivated for an extended time period in CELLine (10 weeks or more), and the supernatant is harvested
weekly. When a productivity of 1.5 mg/mL is assumed and 20 mL of supernatant are harvested weekly from the cell compartment
of one CELLine, seven harvests are necessary to produce 200 mg of MAb. Because 1.0 L of medium is exchanged weekly in its
compartment, the total medium consumption is 7.0 L for this compartment, plus 140 mL for the cell compartment.
Production costs listed in the second section of Table 2 were calculated according to these parameters and are subdivided
into expenses for disposables, equipment amortization, medium, serum, and labor. With regards to disposable costs, a bioreactor
is relatively expensive. However, similarly high are the expenses estimated for the purchase of 17 roller bottles. Concerning
equipment costs, standard cell culture laboratory equipment (such as incubator and microscope) has not been considered because
this equipment is required regardless which culture system used. When using CELLine, no additional equipment is needed, whereas
amortization costs accrue for the roller apparatus and the stirred bioreactor. To calculate costs, a depreciation period
of five years and an average number of 30 production runs per year have been assumed, so with an initial investment of €3,000
(approximately $3,700) for the roller apparatus and €20,000 (approximately $24,668) for the stirred bioreactor, amortization
costs per run are €20 and €133.3 (approximately $25 and $164), respectively.
Regarding medium costs, the use of CELLine involves consumption and consequently costs that are approximately 40 percent higher
than conventional systems. Significantly less serum is necessary because most growth-stimulating components in serum are too
large to diffuse through the semi-permeable membrane and it is common practice to supplement only the cell compartment with
serum and to reduce or completely omit serum supplementation of the medium compartment.2 A one percent serum supplementation of the medium in the medium compartment (70 mL serum) has been assumed, because this
is often done to reduce osmotic pressure generated by unequal supplementation of the two compartments. Assuming a 10 percent
serum supplementation of the medium in the cell compartment, an additional 14 mL of serum is necessary for CELLine, resulting
in a total consumption of 84 mL serum. This represents a six-fold reduction of serum consumption (and costs) when compared
to the 500 mL serum needed for non-compartmentalized systems.
Table 2. Cost Analysis in Euros for Production of 200 mg of MAb Using CELLine or Conventional One-Compartment Systems
To calculate labor costs, a wage of €40/hr (approximately $49.33/hr) has been assumed, and the handling time for inoculation
and supernatant harvesting has been estimated based on the feedback of different users. The time necessary for handling CELLine
amounts to 20 min per bioreactor and harvest, the handling of one roller bottle requires 15 min, and the use of the stirred
bioreactor, including cleaning and sterilization, is estimated to require a total of eight hr. Despite the fact that the handling
time for one roller bottle is 25 percent lower than for one CELLine, the larger number of bottles requires a total handling
time of 265 min, or nearly twice as much as for seven CELLine harvests (140 min).