Early trials applying the XD process for an IgG-producing CHO clone resulted in a viable cell density of approximately 60 x 106 cells/mL and 12.6 g/L of antibody. In addition, it was found that by shortening the cultivation period to 15 days, operational costs were reduced and risks associated with long processes (e.g., contamination and technical failures) diminished.
Another advantage of XD is that as a result of production improvements, the overall capacity of a manufacturing plant may be reduced if the same output of product is desired, decreasing plant footprint, equipment, and facility-related investments. Also, because product is collected inside the bioreactor, only a small and concentrated batch is harvested, thus eliminating the need to collect and purify large, multiple volume harvest batches.
In another experiment, a CHO clone engineered to produce and secrete a fusion protein was tested. The original fed-batch process from the customer utilized commercially available, chemically defined medium and feeds, and reported a maximum product concentration of only 1.2 g/L in fed-batch mode.
By applying XD process technology, with the same basal medium, a biomass concentration of 130 x 106 cells/mL was attained (Figure 2). The high cell growth in the XD bioreactor translated into a 7.7-fold improvement in productivity (final product concentration of 9.2 g/L).
The benefits of boosting the productivity of the bioreactor are obvious. The original fed-batch process utilized a 400 L bioreactor that delivered 480 grams of recombinant product. Using XD process technology the same amount of product was obtained by using a 50 L working volume bioreactor. Even higher productivity was obtained in a second run using the same CHO clone.