Hollow Fiber Cell Culture Systems for Economical Cell-Product Manufacturing

Hopkinson, John

doi:10.1038/nbt0385-225

Cited by 45 publications

(13 citation statements)

References 13 publications

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“…Similarly, macromolecules in the perfusing media remain within the fiber lumina. Harvest ports provide access to the extracapillary space for examination of cells and harvest of cell secreted products (22,45). (22,26).…”

Section: Hollow Fiber Bioreactorsmentioning

confidence: 99%

“…Purity of the antibody product has been facilitated by gradual serum reduction in the culture medium which has been achieved in hollow fiber systems without significant inhibitory effect on production (42,45,46,50,51).…”

Section: Schematic Diagram Of a Hollow Fiber Bioreactormentioning

confidence: 99%

“…It should be noted that of the hollow fiber bioreactor publications cited, only 2 described commercially available systems similar to the small scale systems that were used in the current study (45,46 Each of the five hybridoma cell lines was grown in a group of 20 mice to provide data on monoclonal antibody production in murine ascites. Additionally, three of these cells lines, 2B11, 3C9, and RMK, were also grown in each of three different hollow fiber bioreactor systems to provide comparative production data from these in vitro systems.…”

Section: \\mentioning

confidence: 99%

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Evaluation of hollow fiber bioreactors as an alternative to murine ascites production for small scale monoclonal antibody production

Jackson

Trudel

Fox

et al. 1996

Journal of Immunological Methods

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Monoclonal antibody (MAb) production via the growth of ascitic tumors in mice has been the time-honored technique for producing small scale, research laboratory quantities of MAbs. There are many disadvantages associated with MAb production in murine ascites, including animal welfare concerns. Small scale, commercially available, hollow fiber bioreactor systems, which appear to have advantages over other in vitro cell culture techniques, have recently been introduced. To the author's knowledge, these bioreactor systems have not been independently evaluated as a potential alternative to the in vivo production of MAbs in murine ascites. The first objective of this study was to characterize the clinicopathologic changes in mice associated with the in vivo production of MAbs. Five different hybridoma cell lines were grown in groups of 20 mice. Mice were primed with 0.5 ml pristane intraperitoneally 14 days prior to inoculation of 1 x 106 hybridoma cells.Abdominal paracentesis was performed a maximum of 3 times for collection of ascites from each mouse; ascites volumes were recorded. Clinical observations, body weight measurements, and postmortem examinations were performed. Incidence and severity of clinical abnormalities increased with time. Disseminated intraabdominal seeding of tumor and/or solid tumor masses were observed at postmortem examination. The second objective of the study was to compare MAb production in mice versus hollow fiber bioreactor systems to determine the feasibility of these systems as potential alternatives to the use of mice. Three hybridoma cell lines were grown in each of three different commercially available hollow fiber bioreactor systems and in groups of 20 mice. Bioreactors were harvested 3 times weekly for 65 days and were monitored by cell counts, cell viability and media glucose consumption. Time and materials logs were maintained. Time spent in labor and materials costs were greater for the bioreactors than the mice. The mean antibody concentration, as determined by ELISAs, in mouse ascites versus the range of mean concentrations for the 3 bioreactor systems for each cell line were as follows: cell line 2B11, 4.22 mg/ml vs. 0.71 to 1.31 mg/ml; cell line 3C9, 4.07 mg/ml vs. 1023.06 mg. Significant clinicopathologic changes in mice were associated with MAb production in ascites. Although time and materials costs were greater for the bioreactors, these results suggest that hollow fiber bioreactor systems merit further investigation as potentially viable alternatives to the use of mice for MAb production.2 ACKNOWLEDGEMENTS

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Section: Hollow Fiber Bioreactorsmentioning

confidence: 99%

Section: Schematic Diagram Of a Hollow Fiber Bioreactormentioning

confidence: 99%

Section: \\mentioning

confidence: 99%

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Evaluation of hollow fiber bioreactors as an alternative to murine ascites production for small scale monoclonal antibody production

Jackson

Trudel

Fox

et al. 1996

Journal of Immunological Methods

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“…FiberCell, Amicon, Endotronics systems) (Whitford and Cadwell 2009) and two-compartment dialysis membrane bioreactors (e.g. CeLLine, MiniPerm) during the 1980s and 1990s, the production of diagnostic and therapeutic antibodies in the one and two-digit mg-range became possible (Hopkinson 1985;Falkenberg 1998;Marx 1998;Brecht 2010). The breakthrough for SU bioreactors was marked by the introduction of wave-mixed systems, the first model of which, the WAVE BIOREACTOR, was launched in the late 1990s.…”

Section: Introductionmentioning

confidence: 98%

Single-Use Bioreactors for Animal and Human Cells

et al. 2014

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Single-use (SU) bioreactors are being increasingly used in production processes based on animal (i.e. mammalian and insect) and human cells. They are particularly suitable for the production of high-value products on small and medium scales, and in cases where fast and safe production is a requirement. Thus, it is not surprising that SU bioreactors have established themselves for screening studies, cell expansions, and product expressions where they are used for the production of pre-clinical and clinical samples of therapeutic antibodies and preventive vaccines. Furthermore, recent publications have revealed the potential of SU bioreactors for the production of cell therapeutics using human mesenchymal stem cells (hMSCs).This chapter provides a perspective on current developments in SU bioreactors and their main applications. After briefly introducing the reader to the basics of SU bioreactor technology (terminology, historical milestones and characteristics compared to their reusable counterparts) an overview of the categories of currently available SU bioreactor types is provided. SU bioreactor instrumentation is then examined, before discussing well-established and novel applications of SU bioreactors for animal and human cells. This includes descriptions of the engineering characteristics of often-used types of SU bioreactors, covering wave-mixed, stirred, orbitally shaken systems and fixed-bed systems. In this context, the scaling-up of geometrically and non-geometrically similar SU bioreactors is also addressed.

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“…[1][2][3][4][5] They are noncrystalline polymers; their chain rigidity is derived from the relatively inflexible and immobile phenyl and SO 2 groups, whereas their toughness is derived from the connecting ether oxygen. 6 The application of PSF is focused on blood-contact devices (e.g., hemodialysis, hemodiafiltration, and hemofiltration in the form of membranes), [7][8][9][10] cell-and tissue-contact devices (e.g., bioreactors made of hollow-fiber membranes), [11][12][13] and nerve generation (through semipermeable, hollow PSF membranes). [14][15][16] Although these materials have excellent overall properties, their intrinsically hydrophobic nature restricts their use in membrane applications requiring hydrophilicity, such as salinesolution perfusion, artificial kidney membranes, and cell culture bioreactors.…”

Section: Introductionmentioning

confidence: 99%

Surface characterization of quaternized polysulfone films and biocompatibility studies

Ioan¹,

Albu²,

Avram³

et al. 2011

J of Applied Polymer Sci

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A novel quaternized polysulfone with N-dimethyloctylammonium groups was investigated with respect to its surface properties, hydrophobicity, interactions with blood, and morphology. The history of the films formed from N,N-dimethylformamide/methanol and N,Ndimethylformamide/water solutions and the compositions of the solvent/nonsolvent mixtures influenced the surface morphology. Thus, atomic force microscopy investigations of the films showed pores and nodules of different sizes and intensities, which depended on the content of methanol or water in the solvent mixtures. Hydrophilicity modification, evidenced by the apolar components and the electron-acceptor and electron-donor parameters of the polar components of the surface tension parameters, was correlated with atomic force microscopy data. Surface wettability trends were analyzed on the basis of the free energy of hydration between the prepared films and water and the work of adhesion. The adhesion of red blood cells to the modified polysulfone showed the influence of the hydrophobic properties.

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Hollow Fiber Cell Culture Systems for Economical Cell-Product Manufacturing

Cited by 45 publications

References 13 publications

Evaluation of hollow fiber bioreactors as an alternative to murine ascites production for small scale monoclonal antibody production

Evaluation of hollow fiber bioreactors as an alternative to murine ascites production for small scale monoclonal antibody production

Single-Use Bioreactors for Animal and Human Cells

Surface characterization of quaternized polysulfone films and biocompatibility studies

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