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Advances in Large-Scale Biopharmaceutical Manufacturing
and Scale-Up Production*, 2nd Edition

    Design of Large-Scale Cell Culture Process —A Process Engineering Point of View


    There has been significant growth in mammalian cell culture facility demand in the past few years. The scale of the facility has also increased from a few thousand-liter bioreactors, up to tens or twenty thousand-liter bioreactor sizes. These large-scale cell culture facilities tend to be multi-products oriented. As a result, multiple bioreactor trains have to be used to meet the requirement of a defined plant capacity. There are typically three phases of process design for a cell culture facility: conceptual, preliminary and detail engineering. Defining the design basis is the single most important task in the early conceptual design phase of a cell culture plant. To determine the plant capacity for a large-scale cell culture facility, one has to address the following operating options: Facility capability, flexibility, adaptability, expandability, final build-out requirements. Two process support systems, namely CIP (clean-in-place) and SIP (steam-in-place), have crucial impact to the success of facility design. Support operations essential to success of a cell culture facility include inoculum preparation, glasswasher and autoclave operations. The process engineering design for a large-scale cell culture facility is a very complex task. There are a great many design criteria that must be considered. Most of the considerations discussed in this chapter are in context of our experience. In summary, when designing a biotech process, the process engineer must have a full understanding of the client's process, have a 3-D spatial concept, and must be familiar with the specialty GMP valves and its applications. However, it must be emphasized that each and every cell culture plant will have its own specific elements and requirements. It takes a full understanding of the cell culture process, properly applied experience, and collaboration among each member of the design team, which includes all disciplines, to ensure the success of the design.
    Note: This chapter was originally published in the first edition of this study, in its entirety.

    About the Authors

    Chun-Ko Jin*, Tony Cope, Megan Jakobsen, Jennifer Foelske, Kelly Kivett, Teresa Cheung, Greg Francis
    Fluor Daniel Inc., Greenville, SC

    Dr. Chun-Ko Jin, a technical director in Fluor Daniel’s Life Science Division (100 Fluor Daniel Drive, Greenville, SC) has 20 years of experience in biotech/pharmaceutical, fermentation, and enzyme industries, with emphasis on process engineering, process and product development. For the last 16 years, he has been extensively engaged in engineering works for biopharmaceutical industries worldwide. He is experienced in conceptualization, feasibility studies, technical evaluations, design execution for multiproduct and dedicated biotech facilities, as well as largescale fermentation facilities for citric acid, antibiotics and amino acids. Dr. Jin holds a Ph.D. degree in chemical engineering from Rutgers University specializing in biochemical engineering.

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