Foaming and its Control in Bioprocesses

Vardar‐Sukan, Fazilet

doi:10.1007/978-94-011-2468-3_6

Cited by 14 publications

(67 citation statements)

References 27 publications

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“…7±8), since for these two antifoam agents the gas hold-up is markedly decreased (and this strongly suggests an increase on d vs , which unfortunately could not be measured). Thus it is possible that, for addition of these two antifoam agents, the effect on bubble coalescence becomes more important than the effect on surface ten- At higher concentrations, the effect of antifoam addition on k L a has been reported in the literature to be different, i.e., an enhancement has been observed (e.g., Liu et al, 1994;Aibe et al, quoted by Lavery and Nienow, 1987;Vardar-Sukan and Sukan, 1992;Rols et al, 1990). This was con®rmed in this work for soybean oil and silicone, but not for PPG solutions (at least in the range of concentrations studied).…”

Section: Effect Of Antifoam Addition and Concentration On K L Amentioning

confidence: 99%

“…At low concentrations, these substances markedly decrease mass transfer ef®ciency (Kawase and Moo-Young, 1990), while at high concentrations, the opposite may occur (Liu et al, 1994), (Vardar-Sukan and Sukan, 1992). In some cases, excess addition may even be considered for oxygen transfer enhancement, particularly if the antifoam agent is also a nutrient, as in the case of natural oils (Rols and Goma, 1991).…”

Section: Introductionmentioning

confidence: 99%

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Effect of antifoam addition on gas-liquid mass transfer in stirred fermenters

Morão

Maia

Fonseca

et al. 1999

Bioprocess Engineering

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The in¯uence of three well-known antifoaming agents (polypropylene glycol, silicone and soybean oil) on gas-liquid mass transfer in stirred tanks is studied, both in model and in fermentation media. The effect of antifoam concentration, ionic strength, viscosity, agitation speed and gas¯ow rate are investigated. It is found that antifoam addition at low concentrations markedly decreases the gasliquid volumetric mass transfer coef®cient, k L a, for the three antifoam agents tested. Although the major effect is on the ®lm coef®cient k L , some effect is also detected on the speci®c area, a. It is found that the in¯uence of viscosity and antifoam addition are not cumulative: each tends to attenuate the other's effect on mass transfer. Both for silicone and for soybean oil, but not for PPG in the concentration range studied, there is an antifoam concentration above which further antifoam addition starts to improve k L a.

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Section: Effect Of Antifoam Addition and Concentration On K L Amentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of antifoam addition on gas-liquid mass transfer in stirred fermenters

Morão

Maia

Fonseca

et al. 1999

Bioprocess Engineering

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“…As much as 30 mL/L of P2000 was required to control foaming above the 3 mL/L initially batched. Foaming, and associated foam control, was a scale-up hindrance, contamination risk, and downstream isolation challenge [20][21][22][23][24][25].…”

Section: Resultsmentioning

confidence: 99%

Pilot-scale process development and scale up for antifungal production

Junker

Walker

Hesse

et al. 2008

Bioprocess Biosyst Eng

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A pilot-scale fermentation was developed for an antifungal compound produced by a filamentous fungus. Replacement of galactose with lactose (20-fold cost savings) and a threefold phosphate reduction (15 to 5 g/L) improved productivity 2.5-fold. Addition of supplements--glycine, cobalt chloride, and trace elements--resulted in a further twofold productivity increase, greater process robustness, and less foaming which reduced antifoam addition tenfold (30 to <3 mL/L). Mid-cycle lactose limitations were addressed by raising initial lactose levels (40 to 120 g/L) resulting in another twofold productivity increase. Overall, peak titers increased tenfold from 45 +/- 9 to 448 +/- 39 mg/L, and productivities improved from 3 to 25 mg/L day. Despite its high productivity, process scale up was challenged by high broth viscosity (5,000-6,000 cP at 16.8 s(-1)). Gassed power requirements at the 600 L scale (4.7 kW/1,000 L) exceeded available power at the 15,000 L scale (3.0 kW/1,000 L), and broth transfer to the downstream isolation facility was hindered. Mid-cycle broth dilution with up to five 10 vol% additions of 12 wt% lactose solution or whole medium-reduced viscosity three- to fivefold (1,000-1,500 cP at 16.8 s(-1)), gassed power within scale-up limits (2.5 kW/1,000 L), and peak titer by up to 45%. The process was scaled up to the 15,000 L working volume based on constant aeration rate (vvm) and peak impeller tip speed, raising superficial velocities at similar shear. This strategy maximized mass transfer rates at target gassed power per unit volume levels, and along with controlled broth viscosity, precluded multiple dilution additions. A final titer of 333 mg/L with one dilution addition was achieved, somewhat lower than expected, likely owing to inhibition from some unmeasured volatile compound (not believed to be carbon dioxide) during an extended period of high back-pressure in the early production phase.

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“…Foam formation as well as its growth, stability, and inhibition are dependent on a combination of different cell culture solution properties and bioreactor operating conditions. [1][2][3][4][5] These factors include solution properties such as medium composition, cell density, cell viability, cell growth, and titer, in addition to bioreactor operating conditions such as gas flow rate, sparger orifice size, agitation rate, temperature, and vessel geometry. 3 While some foam can be tolerated, excessive foam accumulation can significantly lower operational efficiency and overall protein production.…”

Section: Introductionmentioning

confidence: 99%

“…Many physical and mechanical foam breaking strategies can be detrimental to cell culture performance and are not typically implemented in biopharmaceutical applications. 3,5 While foam reduction can be achieved by increasing back-pressure, decreasing agitation, and/or decreasing gas sparge rates, these types of modifications to process operating conditions can adversely affect product titers. 3 Chemical antifoams are a less stressful means of controlling foam proliferation that offer the end-user simple, convenient, economical, and commercially-available options that can be implemented in a manufacturing environment.…”

Section: Introductionmentioning

confidence: 99%

Endotoxin inactivation via steam‐heat treatment in dilute simethicone emulsions used in biopharmaceutical processes

Britt

Galvin

Gammell

et al. 2014

Biotechnology Progress

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Simethicone emulsion is used to regulate foaming in cell culture operations in biopharmaceutical processes. It is also a potential source of endotoxin contamination. The inactivation of endotoxins in dilute simethicone emulsions was assessed as a function of time at different steam temperatures using a Limulus amebocyte lysate kinetic chromogenic technique. Endotoxin inactivation from steam-heat treatment was fit to a four-parameter double exponential decay model, which indicated that endotoxin inactivation was biphasic, consisting of fast and slow regimes. In the fast regime, temperature-related effects were dominant. Transitioning into the slow regime, the observed temperature dependence diminished, and concentration-related effects became increasingly significant. The change in the Gibbs free energy moving through the transition state indicated that a large energy barrier must be overcome for endotoxin inactivation to occur. The corresponding Arrhenius pre-exponential factor was >>10(12) s(-1) suggesting that endotoxins in aqueous solution exist as aggregates. The disorder associated with the endotoxin inactivation reaction pathway was assessed via the change in entropy moving through the transition state. This quantity was positive indicating that endotoxin inactivation may result from hydrolysis of individual endotoxin molecules, which perturbs the conformation of endotoxin aggregates, thereby modulating the biological activity observed. Steam-heat treatment decreased endotoxin levels by 1-2 logarithm (log) reduction (LRV), which may be practically relevant depending on incoming raw material endotoxin levels. Antifoam efficiency and cell culture performance were negligibly impacted following steam-heat treatment. The results from this study show that steam-heat treatment is a viable endotoxin control strategy that can be implemented to support large-scale biopharmaceutical manufacturing.

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Foaming and its Control in Bioprocesses

Cited by 14 publications

References 27 publications

Effect of antifoam addition on gas-liquid mass transfer in stirred fermenters

Effect of antifoam addition on gas-liquid mass transfer in stirred fermenters

Pilot-scale process development and scale up for antifungal production

Endotoxin inactivation via steam‐heat treatment in dilute simethicone emulsions used in biopharmaceutical processes

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