Figure 3. Sequence of unit operations for a typical MAb production process
In this study, we evaluate the total CoG when the reusable AEX column chromatography was replaced by disposable membrane chromatography
in a production process. The production process included upstream, recovery, and purification, and all unit operations were
based on stainless steel equipment with the exception of the disposable Q membrane step in the disposable option (Figure 3).
The process sequence was based on the manufacture of a mammalian-based MAb using generic production steps, derived from commercially
relevant operations commonly practiced in the industry.
The mammalian production cell culture is performed in fed-batch mode with two batch seed cell culture steps. The growth and
production medium is DMEM medium with additives. The feeds are glucose and glutamine solutions. Removal of the cells is achieved
by centrifugation and depth filtration. The downstream purification steps are standard industrial unit operations for the
production of an antibody-based product, using routine solutions and cycle times.
Table 1. Mass balance calculations
The study assumes a 2,000 L process scale with 2 g/L MAb expression titer. Table 1 shows the feed mass (3,027 g) into the
AEX chromatography unit operation. Load densities of 10 kg/L for the membrane adsorbers and up to 100 g/L for the Q-column
were selected. Both devices were used in the FT mode. With these assumptions, 3,027 g of product would require a 20-inch Sartobind
Q capsule with 360 mL membrane volume against a 30-L column volume (20 cm bed height) of Q sepharose FF (GE Healthcare Bio-Sciences
Table 2. Subunit operation steps for a) reusable resin-based chromatography and b) disposable membrane chromatography
The basis for the case study comparison is the steps used to define the chromatography operation (flush, equilibration, and
wash). The buffers used for the disposable membrane operation are similar to that in the conventional resin-based chromatography
case. Table 2 shows the subunit operations and the solution requirements for (a) the reusable column chromatography and (b)
the disposable membrane chromatography. The stainless steel chromatography column requires cleaning and storage steps. The
disposable nature of the membrane technology has eliminated the need for cleaning and washing, thereby reducing the amount
of solutions required.