Non-specific binding and saturation of Polysorbate-20 with aseptic filter membranes for drug substance and drug product during mAb production

Zhou, Joe; Qiu, Jinshu; Jiang, Ge; Zhou, Chengfeng; Bingham, N. E.; Yeung, Helena; Dransart, Bryan; Wadhwa, Manpreet-Vick S; Tressel, Tim

doi:10.1016/j.memsci.2008.08.046

Cited by 27 publications

(36 citation statements)

References 15 publications

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“…Dual‐layer (PES over PVDF) filters, such as Fluorodyne ® EX showed similar adsorption level as hydrophilized PVDF filters. These findings agreed with published reports that more PS‐20 (or PS‐80) was adsorbed by PES material than PVDF material . According to these reports, the presence of protein at common concentrations (2–150 mg/mL) does not affect the adsorption of PS‐20 or PS‐80 on sterilizing filters .…”

Section: Discussionsupporting

confidence: 92%

“…These findings agreed with published reports that more PS‐20 (or PS‐80) was adsorbed by PES material than PVDF material . According to these reports, the presence of protein at common concentrations (2–150 mg/mL) does not affect the adsorption of PS‐20 or PS‐80 on sterilizing filters . The differences among different types of filters are possibly related to the differences in the hydrophobicity of membrane materials.…”

Section: Discussionsupporting

confidence: 91%

“…AcroPak ® 1000 and Opti‐Cap ® SHC membranes requires more than 100 μg/cm 2 PS‐20 to reach saturation point while other three hydrophilized PVDF membranes required less than 100 μg/cm 2 PS‐20 to saturate. The amount of adsorbed PS‐20 is in the same scale as published data . According to the manufacturer, Fluorodyne ® EX is a combination of an upstream layer of PES over a PVDF membrane, but its behavior resembles hydrophilized PVDF material.…”

Section: Discussionmentioning

confidence: 88%

“…Among them, membrane filters with 30 kDa and 10 kDa MWCO are commonly used in a tangential flow filtration (TFF) process step for protein concentration and small molecule removal, and membrane filters with a 0.2 μm pore size are usually used to remove bacteria in sterilizing filtration steps. It has been reported that PS‐20 will be adsorbed on the sterilizing filters, and the amount adsorbed is dependent on the membrane material . However, neither the amount of adsorption nor composition of PS‐20 after sterilizing filtration has been reported.…”

Section: Introductionmentioning

confidence: 99%

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The effects of membrane filters used in biopharmaceutical processes on the concentration and composition of polysorbate 20

Lei¹,

Hewitt²,

Cornell³

et al. 2013

Biotechnology Progress

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Polysorbate 20 (PS-20) is often included in the formulation for therapeutic proteins to reduce protein aggregation and surface adsorption. During the production process of therapeutic proteins, various membrane filters are used to filter product pools containing PS-20. The purpose of this study is to quantify the effects of these membrane filtration processes on the concentration and composition of PS-20. A quantitative understanding of this process provides the knowledge base for better controlling the consistency of formulation excipients in drug products. PS-20 solutions (without protein) were filtered through either 0.2 µm sterilizing filters or membrane filters with 30 kDa MWCO. The concentration of PS-20 was measured by a mixed-mode chromatography method and a nuclear magnetic resonance spectroscopy (NMR) assay. The composition of PS-20 was characterized by (1) H-NMR and a reverse-phase chromatography method. Non-specific adsorption of PS-20 on both the sterilizing filter and 30 kDa MWCO membrane filter was quantified. Composition of PS-20 was altered after 30 kDa MWCO membrane filtration, possibly because the different interactions between heterogeneous PS-20 components and the 30 kDa MWCO membrane were not uniform. As a result, the retentate after the 30 kDa MWCO membrane filtration step contains no POE sorbitan and increased amount of POE sorbitan di-esters and tri-esters.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The effects of membrane filters used in biopharmaceutical processes on the concentration and composition of polysorbate 20

Lei¹,

Hewitt²,

Cornell³

et al. 2013

Biotechnology Progress

View full text Add to dashboard Cite

show abstract

“…A previous study did not find any significant adsorption of polysorbate 20 to lab‐scale filters,32 but the effect observed in this investigation is significant. Another study, also found adsorption of polysorbate to sterilizing‐grade filters 36. Zhou et al reported specific binding of polysorbate 20 of ∼70 µg/cm 2 to PES membranes (Sartopore 2).…”

Section: Resultsmentioning

confidence: 88%

Adsorption Behavior of a Surfactant and a Monoclonal Antibody to Sterilizing-Grade Filters

Mahler

Huber

Kishore

et al. 2010

Journal of Pharmaceutical Sciences

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Implementation of Advanced Technologies in Commercial Monoclonal Antibody Production

Zhou¹,

Tressel

Yang

et al. 2013

Modern Biopharmaceuticals

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Non-specific binding and saturation of Polysorbate-20 with aseptic filter membranes for drug substance and drug product during mAb production

Cited by 27 publications

References 15 publications

The effects of membrane filters used in biopharmaceutical processes on the concentration and composition of polysorbate 20

The effects of membrane filters used in biopharmaceutical processes on the concentration and composition of polysorbate 20

Adsorption Behavior of a Surfactant and a Monoclonal Antibody to Sterilizing-Grade Filters

Implementation of Advanced Technologies in Commercial Monoclonal Antibody Production

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