Endotoxin removal by charge-modified filters

Gerba, Charles P.; Hou, Kenneth C.

doi:10.1128/aem.50.6.1375-1377.1985

Cited by 35 publications

(23 citation statements)

References 5 publications

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“…However, this mode of filtration is known to demonstrate removal of soluble impurities as well. Some of the earlier studies have reported the use of depth filtration to clear endotoxins from water (Gerba, ) and for clearance of DNA from cell culture supernatants (Charlton et al, ). Yigzaw et al thoroughly investigated the ability of depth filters to reduce the amount of HCP and DNA through optimization of the harvest clarification step (Yigzaw, ).…”

Section: Depth Filtrationmentioning

confidence: 99%

Clarification technologies for monoclonal antibody manufacturing processes: Current state and future perspectives

Singh

Arunkumar

Chollangi

et al. 2015

Biotech & Bioengineering

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Considerable progress has been made increasing productivity of cell cultures to meet the rapidly growing demand for antibody biopharmaceuticals through increased cell densities and longer culture times. This in turn has dramatically increased the burden of process and product related impurities on the purification processes. In addition, current trends in the biopharmaceutical industry point toward both increased productivity and targeting smaller patient populations for new indications. Taken together, these developments are driving the industry to explore alternative separation technologies as a future manufacturing strategy. Clarification technologies well established in other industries, such as flocculation and precipitation are increasingly considered as a viable solution to address this bottleneck in antibody processes. However, several technical issues need to be fully addressed including suitability as a platform application, robustness, process cost, toxicity, and clearance. This review will focus on recent efforts to incorporate new generation clarification technologies for mammalian cell cultures producing monoclonal antibodies as well as challenges to their implementation supported by a case study.

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Section: Depth Filtrationmentioning

confidence: 99%

Clarification technologies for monoclonal antibody manufacturing processes: Current state and future perspectives

Singh

Arunkumar

Chollangi

et al. 2015

Biotech & Bioengineering

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“…Owing to their charge and hydrophobic characteristics, depth filters have been applied to remove endotoxin, DNA, host cell proteins and potential adventitious agents such as viral particles and prions. Depth filters have been used for the removal of endotoxin from water (43) and DNA from cell culture supernatant (44). Positively charged depth filters have also been used to reduce host cell protein through ionic and hydrophobic interactions and prevent the fouling of the subsequent capture column (31).…”

Section: Depth Filtrationmentioning

confidence: 99%

Advances in Primary Recovery: Centrifugation and Membrane Technology

Roush

2008

Biotechnology Progress

121

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Significant and continual improvements in upstream processing for biologics have resulted in challenges for downstream processing, both primary recovery and purification ( 1). Given the high cell densities achievable in both microbial and mammalian cell culture processes, primary recovery can be a significant bottleneck in both clinical and commercial manufacturing. The combination of increased product titer and low viability leads to significant relative increases in the levels of process impurities such as lipids, intracellular proteins and nucleic acid versus the product. In addition, cell culture media components such as soy and yeast hydrolysates have been widely applied to achieve the cell culture densities needed for higher titers ( 2, 3). Many of the process impurities can be negatively charged at harvest pH and can form colloids during the cell culture and harvest processes. The wide size distribution of these particles and the potential for additional particles to be generated by shear forces within a centrifuge may result in insufficient clarification to prevent fouling of subsequent filters. The other residual process impurities can lead to precipitation and increased turbidity during processing and even interference with the performance of the capturing chromatographic step. Primary recovery also poses significant challenges owing to the necessity to execute in an expedient manner to minimize both product degradation and bioburden concerns. Both microfiltration and centrifugation coupled with depth filtration have been employed successfully as primary recovery processing steps. Advances in the design and application of membrane technology for microfiltration and dead‐end filtration have contributed to significant improvements in process performance and integration, in some cases allowing for a combination of multiple unit operations in a given step. Although these advances have increased productivity and reliability, the net result is that optimization of primary recovery processes has become substantially more complicated. Ironically, the application of classical chemical engineering approaches to overcome issues in primary recovery and purification (e.g., turbidity and trace impurity removal) are just recently gaining attention ( 4). Some of these techniques (e.g., membrane cascades, pretreatment, precipitation, and the use of affinity tags) are now seen almost as disruptive technologies ( 5). This paper will review the current and potential future state of research on primary recovery, including relevant papers presented at the 234th American Chemical Society (ACS) National Meeting in Boston.

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“…Electrostatic attraction between the proteins and the charged polymeric binder, as well as hydrophobic interaction, have been examined as relevant retention mechanisms (Charlton, Relton, & Slater, 1999;Yigzaw et al, 2006). For instance, the removal of colloidal impurities such as endotoxin from water (Gerba & Hou, 1985) and DNA from buffered solutions (Eschrich, Cyr, & Dorsey, 1997) was correlated with the degree to which the depth filters were charged.…”

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confidence: 99%

Contributions of depth filter components to protein adsorption in bioprocessing

Khanal

Singh

Traylor

et al. 2018

Biotech & Bioengineering

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Depth filtration is widely used in downstream bioprocessing to remove particulate contaminants via depth straining and is therefore applied to harvest clarification and other processing steps. However, depth filtration also removes proteins via adsorption, which can contribute variously to impurity clearance and to reduction in product yield. The adsorption may occur on the different components of the depth filter, that is, filter aid, binder, and cellulose filter. We measured adsorption of several model proteins and therapeutic proteins onto filter aids, cellulose, and commercial depth filters at pH 5-8 and ionic strengths <50 mM and correlated the adsorption data to bulk measured properties such as surface area, morphology, surface charge density, and composition. We also explored the role of each depth filter component in the adsorption of proteins with different net charges, using confocal microscopy. Our findings show that a complete depth filter's maximum adsorptive capacity for proteins can be estimated by its protein monolayer coverage values, which are of order mg/m , depending on the protein size. Furthermore, the extent of adsorption of different proteins appears to depend on the nature of the resin binder and its extent of coating over the depth filter surface, particularly in masking the cation-exchanger-like capacity of the siliceous filter aids. In addition to guiding improved depth filter selection, the findings can be leveraged in inspiring a more intentional selection of components and design of depth filter construction for particular impurity removal targets.

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Endotoxin removal by charge-modified filters

Cited by 35 publications

References 5 publications

Clarification technologies for monoclonal antibody manufacturing processes: Current state and future perspectives

Clarification technologies for monoclonal antibody manufacturing processes: Current state and future perspectives

Advances in Primary Recovery: Centrifugation and Membrane Technology

Contributions of depth filter components to protein adsorption in bioprocessing

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