THE NEW ANTIBODY PLANT
The basic production process used in the new plant is very similar to standard reported antibody production schemes. Cell
culture and fermentation are carried out in a continuous perfusion mode that lasts for several months, with harvests being
collected at regular intervals. The purification scheme starts with a capture step based on Protein A chromatography, followed
by several chromatography steps for contaminant removal and product polishing. Adequate viral reduction is achieved by viral
(nano) filtration as well as by viral inactivation steps along with the chromatographic operations.
The plant was designed with two segregated production trains, which each have 2,000 L of fermentation capacity. This setup
allows two products to be manufactured simultaneously. The layout was organized to facilitate liquid handling in bags at large
scale, based on experience with our current process. Cell culture medium and buffers are stored in a central service corridor,
from where all the process rooms are fed through a closed liquid distribution system (Figure 1). This open space allows for
flexible allocation of movable pallet tanks with bag containers up to 2,500 L. Larger bags are not available, however, so
fixed stainless-steel tanks are used for volumes of 3,000 L and greater. A significant reduction of highly controlled cleanroom
space was achieved with this approach.
Liquid storage in bags accounts for the most extended use of disposable elements in the hybrid facility. Table 1 describes
the level of substitution of stainless steel tanks by disposable containers in the various steps of the manufacturing process
in this model. Disposable bags replaced 73% of the total liquid storage capacity of the plant, estimated at 117 m3 and distributed over more than a hundred process vessels. Other disposable elements were also introduced, such as chromatographic
membranes and disposable viral filtration, but those had a limited effect on equipment cost savings.
Table 1. Vessel types used in the stainless steel (SS) and hybrid (HYB) models.
ESTIMATE OF CAPITAL INVESTMENT
Figure 2 shows the total capital costs for constructing a 100 kg antibody plant under each project alternative. This calculation
started with a detailed estimate of equipment purchase costs (PC) based on recent price quotes. Prices were corrected for
volume and currency depreciation where needed. To avoid significant distortions of the results because of land prices and
construction costs in Cuba, the total capital costs were calculated using Lang coefficients, as updated by Petrides for the
biotech sector.3,4 This method makes it possible to calculate the various items of the capital cost based on the equipment purchase cost using
several multipliers (or coefficients). The use of these coefficients for disposable and stainless-steel technology has been
discussed in the past by various authors.1,4
After making the calculations for our case study using the combination of the selected Lang coefficients, we found that direct
fixed capital was seven times greater than the equipment purchase cost for the stainless steel project alternative, but only
five times greater in the hybrid alternative, similar to the estimates obtained by Farid.1 These results correspond to our experience that a significant reduction in facility complexity is achieved when disposable
technology is used extensively throughout the manufacturing process.
As can be seen in Figure 2, equipment purchase costs in the hybrid project were 34% lower than in the stainless steel project,
which in turn reduced the total capital cost by 54% compared to the stainless steel alternative. This result demonstrates
the significant capital savings that can be achieved through a broad integration of disposables in a medium-sized biopharmaceutical