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Review
. 2018:165:95-114.
doi: 10.1007/10_2016_54.

Manufacturing of Proteins and Antibodies: Chapter Downstream Processing Technologies

Richard Turner  1 , Adrian Joseph  2 , Nigel Titchener-Hooker  2 , Jean Bender  3
Affiliations
Review

Manufacturing of Proteins and Antibodies: Chapter Downstream Processing Technologies

Richard Turner et al. Adv Biochem Eng Biotechnol. 2018.

Abstract

Cell harvesting is the separation or retention of cells and cellular debris from the supernatant containing the target molecule Selection of harvest method strongly depends on the type of cells, mode of bioreactor operation, process scale, and characteristics of the product and cell culture fluid. Most traditional harvesting methods use some form of filtration, centrifugation, or a combination of both for cell separation and/or retention. Filtration methods include normal flow depth filtration and tangential flow microfiltration. The ability to scale down predictably the selected harvest method helps to ensure successful production and is critical for conducting small-scale characterization studies for confirming parameter targets and ranges. In this chapter we describe centrifugation and depth filtration harvesting methods, share strategies for harvest optimization, present recent developments in centrifugation scale-down models, and review alternative harvesting technologies.

Keywords: Capillary shear; Centrifugation; Continuous centrifugation; Depth filter; Disk-stack centrifuge; Filter capacity; Harvest; Mammalian cell; Primary recovery; Scale-down; Sigma factor; Single-use centrifuge; Tangential flow filtration.

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References

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Further Reading
    1. Akeprathumachai S (2004) Murine leukemia virus clearance by flocculation and microfiltration. Biotechnol Bioeng 88:880–889 - DOI
    1. Castilho LR, Medronho RA (2002) Cell retention devices for suspended-cell perfusion cultures. Adv Biochem Eng Biotechnol 74:129–169 - PubMed
    1. Dave P, Dizon-Maspat J, Cano T (2009) Evaluation and implementation of a single-stage multimedia harvest depth filter for a large-scale antibody process. BioProcess Int 7:S8–S17
    1. Hill P, Bender J (2007) Cell harvesting. In: Stacey G, Davis J (eds) Medicines for animal cell cultures. Wiley, Boca Raton
    1. Hove S, Cacace B, Felo M, Chefer K (2010) Development of a robust clarification process for high density mammalian cell culture processes. Recovery of Biological Products XIV, Squaw Creek, Lake Tahoe, August 1–5, 2010

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