Recent advances in ultrafiltration and virus filtration for production of antibodies and related biotherapeutics

Goodrich, Elizabeth; Bohonak, David M.; Genest, P; Peterson, Emily

doi:10.1016/b978-0-08-103019-6.00007-2

Cited by 7 publications

(6 citation statements)

References 44 publications

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“…7A). The absence of significant flow decay demonstrates minimal irreversible fouling by this feedstream, while the reduction of flow can be mainly attributed to reversible fouling through electrostatic interactions and solution viscosity [29,35].…”

Section: Impact Of Filter Fouling Under Manufacturing-like Conditionsmentioning

confidence: 93%

“…1B and C). This pattern can be interpreted as the formation of an internal cake layer, which was most likely triggered by a combination of distinct mechanisms at higher protein concentrations: i) increased pore constriction/intermediate fouling, thus promoting plugging of pores already in the support layer; ii) presence of larger, self-associated fouling species in the feedstream; iii) increased deposition of bulk protein to retained aggregates as nucleation centers [18,24,29]. The simultaneous occurrence of different fouling mechanisms and dynamic shift of foulant deposition across different membrane zones illustrates the complexity of the VF process in the presence of a protein matrix.…”

Section: Impact Of Filter Fouling In Planova 20n At Ph 74mentioning

confidence: 99%

“…Highly pure IgG product intermediates and optimized conditions are essential as even minor portions of subvisual particulates in the feedstream can substantially limit virus filter performance [11,20,28]. Generally, protein concentrations of 5-20 mg/mL represent a reasonable compromise between throughput, flow, and fouling [29,35].…”

Section: Impact Of Filter Fouling Under Manufacturing-like Conditionsmentioning

confidence: 99%

“…Trace quantities of protein species in the feedstream having the propensity to self-associate serve as nucleation sites for continued deposition of bulk protein in the sieving layer of the membrane [18,[24][25][26]. In line with this, the throughput of IgG feedstreams in VF could be considerably improved by using prefilters that remove hydrophobic, self-associating protein species, such as oxidized or degraded IgG forms [22,[27][28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Visualizing protein fouling and its impact on parvovirus retention within distinct filter membrane morphologies

Leisi

Rostami

Laughhunn

et al. 2022

Journal of Membrane Science

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Section: Impact Of Filter Fouling Under Manufacturing-like Conditionsmentioning

confidence: 93%

Section: Impact Of Filter Fouling In Planova 20n At Ph 74mentioning

confidence: 99%

Section: Impact Of Filter Fouling Under Manufacturing-like Conditionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Visualizing protein fouling and its impact on parvovirus retention within distinct filter membrane morphologies

Leisi

Rostami

Laughhunn

et al. 2022

Journal of Membrane Science

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“…Despite this approach, there is still variation in the concentrate-to-filtrate (C/F) signal ratio obtained between different wastewater samples spiked with the same concentration of WTPV (Figure E). This can be caused by the variable filtering efficiency of the device when dealing with viral aggregates , and/or the variable amounts of species with sizes of <20 nm (like heavy metals) in the filtrate, which would create a different value for the blank signal. This variability in the composition of the wastewater samples is evident by the variation in the electrolyte resistance, charge transfer resistance, and double-layer capacitance for the different wastewater samples (Table S4).…”

Section: Resultsmentioning

confidence: 99%

Integrating Water Purification with Electrochemical Aptamer Sensing for Detecting SARS-CoV-2 in Wastewater

Sen

Zhang

et al. 2023

ACS Sens.

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Wastewater analysis of pathogens, particularly SARS-CoV-2, is instrumental in tracking and monitoring infectious diseases in a population. This method can be used to generate early warnings regarding the onset of an infectious disease and predict the associated infection trends. Currently, wastewater analysis of SARS-CoV-2 is almost exclusively performed using polymerase chain reaction for the amplification-based detection of viral RNA at centralized laboratories. Despite the development of several biosensing technologies offering point-of-care solutions for analyzing SARS-CoV-2 in clinical samples, these remain elusive for wastewater analysis due to the low levels of the virus and the interference caused by the wastewater matrix. Herein, we integrate an aptamer-based electrochemical chip with a filtration, purification, and extraction (FPE) system for developing an alternate in-field solution for wastewater analysis. The sensing chip employs a dimeric aptamer, which is universally applicable to the wild-type, alpha, delta, and omicron variants of SARS-CoV-2. We demonstrate that the aptamer is stable in the wastewater matrix (diluted to 50%) and its binding affinity is not significantly impacted. The sensing chip demonstrates a limit of detection of 1000 copies/L (1 copy/mL), enabled by the amplification provided by the FPE system. This allows the integrated system to detect trace amounts of the virus in native wastewater and categorize the amount of contamination into trace (<10 copies/mL), medium (10–1000 copies/mL), or high (>1000 copies/mL) levels, providing a viable wastewater analysis solution for in-field use.

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Residence time distribution in continuous virus filtration

Chen,

Recanati,

De Mathia

et al. 2024

Biotech & Bioengineering

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Regulatory authorities recommend using residence time distribution (RTD) to address material traceability in continuous manufacturing. Continuous virus filtration is an essential but poorly understood step in biologics manufacturing in respect to fluid dynamics and scale‐up. Here we describe a model that considers nonideal mixing and film resistance for RTD prediction in continuous virus filtration, and its experimental validation using the inert tracer NaNO3. The model was successfully calibrated through pulse injection experiments, yielding good agreement between model prediction and experiment ( 0.90). The model enabled the prediction of RTD with variations—for example, in injection volumes, flow rates, tracer concentrations, and filter surface areas—and was validated using stepwise experiments and combined stepwise and pulse injection experiments. All validation experiments achieved 0.97. Notably, if the process includes a porous material—such as a porous chromatography material, ultrafilter, or virus filter—it must be considered whether the molecule size affects the RTD, as tracers with different sizes may penetrate the pore space differently. Calibration of the model with NaNO3 enabled extrapolation to RTD of recombinant antibodies, which will promote significant savings in antibody consumption. This RTD model is ready for further application in end‐to‐end integrated continuous downstream processes, such as addressing material traceability during continuous virus filtration processes.

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Recent advances in ultrafiltration and virus filtration for production of antibodies and related biotherapeutics

Cited by 7 publications

References 44 publications

Visualizing protein fouling and its impact on parvovirus retention within distinct filter membrane morphologies

Visualizing protein fouling and its impact on parvovirus retention within distinct filter membrane morphologies

Integrating Water Purification with Electrochemical Aptamer Sensing for Detecting SARS-CoV-2 in Wastewater

Residence time distribution in continuous virus filtration

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