Evaluating the effect of in-process material on the binding mechanisms of surrogate viral particles to a multi-modal anion exchange resin

Brown, Matthew R.; Burnham, Michael S.; Johnson, Sarah; Lute, Scott; Brorson, Kurt; Roush, David J.

doi:10.1016/j.jbiotec.2017.12.018

Cited by 9 publications

(10 citation statements)

References 12 publications

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“…Specifically, the bacteriophage buffer‐only studies were able to predict both the failure point of the single mode AEX resin as a function of pH and NaCl concentration, as well as the salt tolerant behavior of the multi‐modal AEX resin as a function of relative hydrophobicity. For the in‐process testing, the bacteriophage were able to estimate the loading density where viral breakthrough occurred for all three mAb species and the lack of LRV decline for the reduced impurity loads.…”

Section: Discussionmentioning

confidence: 99%

“…Host cell DNA levels had been previously linked to the breakthrough of viral particles, where it seemed to compete for resin binding potentially via competitive adsorption. Therefore, host cell DNA levels in load, and flow through samples were monitored using a hamster Alu‐like repeat sequence Q‐PCR assay described in detail in previous work for mAb containing experiments.…”

Section: Methodsmentioning

confidence: 99%

“…These studies determined if varied mobile phases produced characteristic binding responses due to a dominating AEX or HIC functional group. To confirm the proposed mechanism, bacteriophage spiked in‐process monoclonal antibody (mAb) pools were tested across buffer conditions, impurity burden, and mAb species . This study identified a minimalistic approach to be able to identify the binding mechanism of viral particles to a multi‐modal anion exchange resin.…”

Section: Introductionmentioning

confidence: 99%

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Defining the mechanistic binding of viral particles to a multi‐modal anion exchange resin

Brown

Burnham

Lute

et al. 2018

Biotechnology Progress

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A multi-tiered approach to determine the binding mechanism of viral clearance utilizing a multi-modal anion exchange resin was applied to a panel of four viral species that are typically used in validating viral clearance studies (i.e., X-MuLV, MVM, REO3, and PrV). First, virus spiked buffer-only experiments were conducted to evaluate the virus's affinity for single mode and multi-modal chromatography resins under different buffer conditions in a chromatography column setting. From these results we hypothesize that the mechanisms of binding of the viruses involve binding to both the hydrophobic and anionic functional groups. This mechanistic view agreed with the general surface characteristics of the different virus species in terms of isoelectric point and relative hydrophobicity values. This hypothesized mechanistic binding was then tested with commercially relevant, in-process materials, in which competitive binding occurred between the load components (e.g., viruses, target product, and impurities) and the resin. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1019-1026, 2018.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Defining the mechanistic binding of viral particles to a multi‐modal anion exchange resin

Brown

Burnham

Lute

et al. 2018

Biotechnology Progress

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“…Equilibration buffer and load conductivity for plate experiments were adjusted by addition of Sodium Chloride to 0, 50, 150, 400, or 600 mM. These levels were chosen after an initial screening (Brown et al, ) to better understand the failure point of Capto Q at the high salt condition for comparison to Capto Adhere and better insight into binding behavior in low salt conditions where IEX interactions are expected to dominate. In addition, the low and high set points (i.e., 0 and 600 mM) of the Sodium Chloride concentrations were chosen as failure points for bacteriophage removal by the single mode resins.…”

Section: Resin Screeningmentioning

confidence: 99%

A step‐wise approach to define binding mechanisms of surrogate viral particles to multi‐modal anion exchange resin in a single solute system

Brown

Johnson

Brorson

et al. 2017

Biotech & Bioengineering

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Multi-modal anion exchange resins combine properties of both anion exchange and hydrophobic interaction chromatography for commercial protein polishing and may provide some viral clearance as well. From a regulatory viral clearance claim standpoint, it is unclear if multi-modal resins are truly orthogonal to either single-mode anion exchange or hydrophobic interaction columns. To answer this, a strategy of solute surface assays and High Throughput Screening of resin in concert with a scale-down model of large scale chromatography purification was employed to determine the predominant binding mechanisms of a panel of bacteriophage (i.e., PR772, PP7, and ϕX174) to multi-modal and single mode resins under various buffer conditions. The buffer conditions were restricted to buffer environments suggested by the manufacturer for the multi-modal resin. Each phage was examined for estimated net charge expression and relative hydrophobicity using chromatographic based methods. Overall, PP7 and PR772 bound to the multimodal resin via both anionic and hydrophobic moieties, while ϕX174 bound predominantly by the anionic moiety. Biotechnol. Bioeng. 2017;114: 1487-1494. © 2017 Wiley Periodicals, Inc.

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“…Zhao et al [76] exploited this property by introducing a Capto adhere MMC step in the multistep chromatography purification process of EV71 VLPs produced from insect cells, following negative CC700 MMC. The Capto adhere-based AEC-HIC step may also contribute to viral clearance by removing adventitious viruses from product streams in downstream purification processes of mAbs and other biopharmaceuticals [209,246,247]. In recent studies, Brown et al [246,247] investigated the binding mechanisms of model virus surrogates (i.e., bacteriophages displaying different surface charge characteristics and hydrophobicities) to the Capto adhere resin.…”

Section: Other Modes (Imac Hic Mmc)mentioning

confidence: 99%

Polysaccharide-based chromatographic adsorbents for virus purification and viral clearance

Junter

Lebrun

2020

Journal of Pharmaceutical Analysis

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Evaluating the effect of in-process material on the binding mechanisms of surrogate viral particles to a multi-modal anion exchange resin

Cited by 9 publications

References 12 publications

Defining the mechanistic binding of viral particles to a multi‐modal anion exchange resin

Defining the mechanistic binding of viral particles to a multi‐modal anion exchange resin

A step‐wise approach to define binding mechanisms of surrogate viral particles to multi‐modal anion exchange resin in a single solute system

Polysaccharide-based chromatographic adsorbents for virus purification and viral clearance

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