The Impact of Cell Culture Medium on Cell Line and Process Development Timelines and Strategies - Animal-component free (ACF) medium sped up cell-line development by eliminating the adaptation period

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The Impact of Cell Culture Medium on Cell Line and Process Development Timelines and Strategies
Animal-component free (ACF) medium sped up cell-line development by eliminating the adaptation period from serum-containing medium used in early development to ACF medium used for high-titer production.


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HuMAb Production with MTCM Media


Figure 4. Comparison of first and second generation MTCM basal media for a HuMAb production using Expression System I
HuMAb batch processes with MTCM A and B were developed that can yield up to 1 g/L without feed addition. In general, MTCM B supports better cell growth and longevity of the culture, and as a result, leads to better productivity in batch and fed-batch processes. For example, Figure 4 shows that, cell culture processes in MTCM B not only reached higher peak cell density, but also expressed higher antibody levels for both batch and fed-batch compared to those in MTCM A.


Figure 5. Fed-batch processes in bioreactors using Expression System II for two different HuMabs. A) MTCM B used as basal medium, combined with MTCM feeds for cell line 1 from Expression System II, with an 11-fold increase in productivity from batch to fed-batch. B) MTCM B used as basal medium, combined with MTCM feed for cell line 2 from Expression System II, with a 10-fold increase in productivity from batch to fed-batch.
Feed formulations and feed strategies have been developed by tailoring them to one or two basic generic processes with MTCM A or B basal media to reach high expression levels. In most cases, when high productivity is demanded in short timelines, these processes only need minimal optimization time. These fed-batch processes range from 2 to 6 g/L HuMAb production with MTCM basal and feed media combinations for cell lines derived from these two expression systems, which can increase productivity up to 11 fold compared to batch cultures (Figures 5 and 6).


Figure 6. Fed-batch processes in bioreactors for Expression System I for two different HuMAbs. MTCM B used as basal medium, combined with MTCM feeds for two cell lines from Expression System I, with a 7-fold increase in viable cell density from batch to fed-batch.
High yield processes also can be developed using commercially available chemically defined basal media along with MTCM feed media (Figure 7). Up to a 13-fold increase in productivity was observed when using commercial basal medium with MTCM feed and feed strategies from our generic processes. However, it is reported that there are usually only 2–5 fold productivity gains from media and process optimization efforts.10


Figure 7. Combination of commercial chemically defined basal media with MTCM feed media for two different HuMAbs. A) Chemically defined CHO basal medium combined with MTCM feed for a cell line from Expression System I with 2,000 nm methotrexate (MTX), showing a 10-fold increase in productivity from batch to fed-batch. B) Chemically defined CHO basal medium combined with commercial feed, compared to MTCM feed for a cell line derived from Expression System II, showing a 3-fold and 13-fold increase, respectively, in productivity from batch to fed-batch.
Using MTCM as a feed medium in combination with commercial basal media from different vendors or using MTCM as a basal medium with different commercial feed media demonstrated the broad applicability of MTCM compositions for high yield upstream processes.


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