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Sep 15, 2011 (Vol. 31, No. 16)

Expression System Gains Lead to High Protein Yields

Current CHO Cell, E.coli, and Yeast Platforms Creating a Healthy Dose of Idle Capacity

  • Implications of Improvements

    Click Image To Enlarge +
    In the future, large-scale biomanufacturing systems are expected to become smaller in size due to the rapid increase in cell culture productivity. [rgerhardt/Shutterstock Images]

    The trend in increasing protein expression yields has had broad ramifications throughout biomanufacturing. From lowering construction requirements, to increasing bottlenecks at the downstream end of production, the effects of upstream advances and the availability of more varied expression systems have created options and problems not previously seen.

    Looking at biological products in the market and in development, the industry still largely restricts its basic expression systems to the three systems it has been using for decades—CHO cells for mammalian cell culture, E. coli for bacterial expression, and yeasts (mostly Saccharomyces).

    With the relatively slow uptake of newer expression systems, many of which offer significantly higher yields and other improvements, the increases in yields now being seen are primarily the result of incremental improvements in these three key systems, including new and optimized vectors, promoters, and cell lines. This is also reflected in the increasing number of companies offering CHO and other common expression system-based bioprocess optimization services.

    Increases in expression yields obviously result in cost savings and improved biomanufacturing efficiency. This has also enabled manufacturers to do more with less, and in many cases do it even better. With expression yields expected to continue to increase, the industry will continue to reap these benefits. Increases in yields also affect facility planning and financing. More importantly, increasing yields and the resultant excess capacity provide needed insurance against costly supply disruptions.

  • Click Image To Enlarge +
    Figure 2. Selected capacity utilization, by production system

    Figure 2 from the survey data shows current capacity utilization rates. There has been a significant reduction in the utilization rates, i.e., increased idle capacity, for mammalian, microbial, and yeast culture since 2003. This year, when asked about average bioprocessing system usage as a percent of operating capacity, those working with mammalian cell reported 61% utilization, bacterial systems users reported 53.6%.

    This indicates that most bioprocessing systems, particularly at larger scale (where most of the capacity is), are now idle much of the time. Capacity utilization rates for lesser-used expression systems were similar, e.g., plant cells (51.3%) and insect cells (59.3%). Overall, capacity utilization rates have stabilized in recent years, with utilization rates for mammalian cell culture steady around 61%–63% for the past five years. The distribution of available mammalian cell culture capacity has changed little in recent years, e.g., with about 60% of respondents reporting total capacity less than 10,000 L.


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