The effects of buffer condition on the fouling behavior of MVM virus filtration of an Fc‐fusion protein

Namila, Fnu; Da, Zhang; Traylor, Steven J.; Nguyen, Tung; Singh, Namrata; Wickramasinghe, Ranil; Qian, Xianghong

doi:10.1002/bit.27085

Cited by 10 publications

(15 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The targeted feed titer for MVM is 9 logs/ml (qPCR) for all the feed conditions. The details on our MVM qPCR assay were described previously (Namila et al, 2019). After the filtration, virus titers in the feed, filtrate and buffer chase were determined by Tissue Culture Infectious Dose 50 (TCID 50 ) assay.…”

Section: Methodsmentioning

confidence: 99%

“…More specifically, virus filtrations are performed at low fluxes where diffusive Brownian motion dominates as well as at high fluxes where hydrodynamics convective force dominates for four commercially available filters. To differentiate the low flux caused by membrane fouling (Namila et al, 2019) and low flux due to a low operating pressure, low‐fouling mAb feed solutions spiked by MVM particles are investigated.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, MVM clearance is found to be product and filter-dependent. Recent studies (Namila et al, 2019;Stuckey et al, 2014) show that virus retention for one of the commercial filters is affected by solution conditions and is product-dependent. Earlier studies (Dishari et al, 2015;LaCasse et al, 2013LaCasse et al, , 2016Willkommen et al, 2013;Woods & Zydney, 2014) have investigated the effects of process interruption or pressure release on virus retention during virus filtration of several commercial virus filters.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The effects of flux on the clearance of minute virus of mice during constant flux virus filtration

Fan

Namila

Sansongko

et al. 2021

Biotech & Bioengineering

Self Cite

View full text Add to dashboard Cite

Constant flux virus filtration experiments were conducted to evaluate minute virus of mice retention behavior of four commercial virus filters for continuous bioprocessing applications. Fluxes chosen were guided by the Peclet number and the processing logistics as well as based on the filter characteristics. At the low flux condition of 5 LM − 2 H − 1 (LMH) when diffusive force dominates, a significant breakthrough was observed for all the filtrate fractions for the filtration of a low fouling monoclonal antibody for three of the four filters. When both diffusive and convective forces are equally important at 40 LMH, virus breakthrough in buffer chase was observed only in one of the four filters investigated. When convective force dominates at 60 LMH or above, a high degree of virus clearance was observed for all three parvovirus filters investigated. Our work shed light on virus clearance during constant flux virus filtration for future continuous biomanufacturing.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The effects of flux on the clearance of minute virus of mice during constant flux virus filtration

Fan

Namila

Sansongko

et al. 2021

Biotech & Bioengineering

Self Cite

View full text Add to dashboard Cite

show abstract

“…21,22 This model was also successfully applied to model the flux decay during virus filtration. 26 The permeate flux and cake resistance are given by the following equations where the symbols are defined in the notation.…”

Section: Modelingmentioning

confidence: 99%

“…The model is based on the classical fouling models 21,22 . This model was also successfully applied to model the flux decay during virus filtration 26 . The permeate flux and cake resistance are given by the following equations where the symbols are defined in the notation.

J = J_{0} ([], e^{- \frac{α ∆ italicpc}{μ R_{m}} t} + \int_{0}^{t} \frac{α ∆ italicpc}{μ (R_{m} + R_{c)}} \times e^{- \frac{α ∆ italicpc}{μ R_{m}} t_{c}} d t_{c}) .

R_{c} = (R_{m} + R_{c 0}) \sqrt{1 + \frac{2 f^{'} α^{'} ∆ italicpc}{μ {(R_{m} + R_{c 0})}^{2}} (t - t_{c})} - R_{m} .

…”

Section: Modelingmentioning

confidence: 99%

Modeling flux in tangential flow filtration using a reverse asymmetric membrane for Chinese hamster ovary cell clarification

Zhang

Patel

Strauss

et al. 2021

Biotechnology Progress

Self Cite

View full text Add to dashboard Cite

Tangential flow filtration is advantageous for bioreactor clarification as the permeate stream could be introduced directly to the subsequent product capture step. However, membrane fouling coupled with high product rejection has limited its use. Here, the performance of a reverse asymmetric hollow fiber membrane where the more open pore structure faces the feed stream and the barrier layer faces the permeate stream has been investigated. The open surface contains pores up to 40 μm in diameter while the tighter barrier layer has an average pore size of 0.4 μm. Filtration of Chinese hamster ovary cell feed streams has been investigated under conditions that could be expected in fed batch operations. The performance of the reverse asymmetric membrane is compared to that of symmetric hollow fiber membranes with nominal pore sizes of 0.2 and 0.65 μm. Laser scanning confocal microscopy was used to observe the locations of particle entrapment. The throughput of the reverse asymmetric membrane is significantly greater than the symmetric membranes. The membrane stabilizes an internal high permeability cake that acts like a depth filter. This stabilized cake can remove particulate matter that would foul the barrier layer if it faced the feed stream. An empirical model has been developed to describe the variation of flux and transmembrane pressure drop during filtration using reverse asymmetric membranes. Our results suggest that using a reverse asymmetric membrane could avoid severe flux decline associated with fouling of the barrier layer during bioreactor clarification.

show abstract

Effect of protein fouling on filtrate flux and virus breakthrough behaviors during virus filtration process

Suh

Jin

Park

et al. 2023

Biotech & Bioengineering

View full text Add to dashboard Cite

Virus filtration process is used to ensure viral safety in the biopharmaceutical downstream processes with high virus removal capacity (i.e., >4 log10). However, it is still constrained by protein fouling, which results in reduced filtration capacity and possible virus breakthrough. This study investigated the effects of protein fouling on filtrate flux and virus breakthrough using commercial membranes that had different symmetricity, nominal pore size, and pore size gradients. Flux decay tendency due to protein fouling was influenced by hydrodynamic drag force and protein concentration. As the results of prediction with the classical fouling model, standard blocking was suitable for most virus filters. Undesired virus breakthrough was observed in the membranes having relatively a large pore diameter of the retentive region. The study found that elevated levels of protein solution reduced virus removal performance. However, the impact of prefouled membranes was minimal. These findings shed light on the factors that influence protein fouling during the virus filtration process of biopharmaceutical production.

show abstract

The effects of buffer condition on the fouling behavior of MVM virus filtration of an Fc‐fusion protein

Cited by 10 publications

References 32 publications

The effects of flux on the clearance of minute virus of mice during constant flux virus filtration

The effects of flux on the clearance of minute virus of mice during constant flux virus filtration

Modeling flux in tangential flow filtration using a reverse asymmetric membrane for Chinese hamster ovary cell clarification

Effect of protein fouling on filtrate flux and virus breakthrough behaviors during virus filtration process

Contact Info

Product

Resources

About