Process Development Strategies and Advantages
The biotechnology industry depends on robust manufacturing cell lines to produce biologics. The timelines for deriving a stable
manufacturing cell line suitable for consistent process scale-up requires thorough screening and subcloning of the initial
transfectant population. In the case of suspension dhfr– CHO cell cultures, amplification procedures using MTX prolongs this process. However, the recombinant cell lines derived
from Expression System II have a more straightforward development time, which can take approximately seven months to adapt
from serum-containing transfection to serum removal and subcloning. Through careful development of MTCM medium that can support
different activities, we were able to significantly reduce the timeline from transfection to cell line selection for both
expression systems (Figure 2). Recombinant cell lines derived from both expression systems can use the same medium without
serum right from the transfection stage. Using one medium throughout all upstream process development phases also helps retain
the higher productivity carried from early clones by eliminating media shifts.
A robust CHO-based high yielding platform technology was established for HuMAb manufacturing. With this strategy, media inventory
became much more streamlined for different process development stages as well as for manufacturing. Basal medium compositions
can be manufactured in both liquid and powder formulations that support growth and production equally well. The powder form
of both basal and feed media has been successfully manufactured up to the 450-kg scale and shown to be stable for more than
two to three years, which has facilitated convenient inventory maintenance for multiple processes of different HuMAb molecules.
Powder formulations provide a convenient means of transport and storage of large batches for commercial-scale manufacturing
and also decrease the costs associated with testing and releasing multiple media lots. Overall, manufacturing efficiency and
timelines are favorably influenced for a wide variety of antibody candidates and also resulted in more operation-friendly
processes by using common media requirements for different CHO cell lines. In addition, knowledge of medium formulations provides
better insights during upstream process optimization. Furthermore, using in-house media can significantly reduce the manufacturing
cost of goods, and medium cost can be lowered as much as 60% compared to commercially available media (Table 3).
Table 3. Comparison of MTCM media costs to commercially available media for different manufacturing scales