Impact of multiple re-use of anion-exchange chromatography media on virus removal

Norling, Lenore A.; Lute, Scott; Emery, Rachel; Khuu, Wynn; Voisard, Mark; Xu, Yuan; Chen, Qi; Blank, G.; Brorson, Kurt

doi:10.1016/j.chroma.2004.09.072

Cited by 87 publications

(54 citation statements)

References 33 publications

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“…In addition to the virus purification literature, there are also published reports describing viral clearance using QSFF resin (Curtis et al, 2003;Norling et al, 2005;Shi et al, 1999bShi et al, , 2004Strauss et al, 2009;Valera et al, 2003). Although most of these do not describe much characterization of the processes used, a few have demonstrated that salt concentration (or conductivity), salt composition, and pH are important factors for viral clearance (Curtis et al, 2003;Strauss et al, 2009).…”

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confidence: 93%

“…One important function of the AEX step is its ability to remove putative viral contaminants and impurities. Virus reduction studies investigating AEX conditions have shown the step to be highly effective at removing both enveloped and non-enveloped viruses, consistently achieving log 10 reduction values (LRVs) greater than 4 (Curtis et al, 2003;Norling et al, 2005;Shi et al, 1999bShi et al, , 2004Strauss et al, 2009;Tayot et al, 1987;Valera et al, 2003;Zolton and Padvelskis, 1984). In order to ensure that this unit operation maintains its ability to remove viruses while allowing for further development of the step, it is important to gain an understanding of the mechanisms by which AEX processes remove viruses from mAb feedstocks.…”

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confidence: 98%

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Understanding the mechanism of virus removal by Q sepharose fast flow chromatography during the purification of CHO‐cell derived biotherapeutics

Strauss

Lute

Tebaykina

et al. 2009

Biotech & Bioengineering

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During production of therapeutic monoclonal antibodies (mAbs) in mammalian cell culture, it is important to ensure that viral impurities and potential viral contaminants will be removed during downstream purification. Anion exchange chromatography provides a high degree of virus removal from mAb feedstocks, but the mechanism by which this is achieved has not been characterized. In this work, we have investigated the binding of three viruses to Q sepharose fast flow (QSFF) resin to determine the degree to which electrostatic interactions are responsible for viral clearance by this process. We first used a chromatofocusing technique to determine the isoelectric points of the viruses and established that they are negatively charged under standard QSFF conditions. We then determined that virus removal by this chromatography resin is strongly disrupted by the presence of high salt concentrations or by the absence of the positively charged Q ligand, indicating that binding of the virus to the resin is primarily due to electrostatic forces, and that any non-electrostatic interactions which may be present are not sufficient to provide virus removal. Finally, we determined the binding profile of a virus in a QSFF column after a viral clearance process. These data indicate that virus particles generally behave similarly to proteins, but they also illustrate the high degree of performance necessary to achieve several logs of virus reduction. Overall, this mechanistic understanding of an important viral clearance process provides the foundation for the development of science-based process validation strategies to ensure viral safety of biotechnology products.

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confidence: 93%

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confidence: 98%

Understanding the mechanism of virus removal by Q sepharose fast flow chromatography during the purification of CHO‐cell derived biotherapeutics

Strauss

Lute

Tebaykina

et al. 2009

Biotech & Bioengineering

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“…It is a powerful tool to remove process-related impurities such as host cell proteins, DNA, endotoxin and leached Protein A, product-related impurities such as dimer/aggregate, endogenous retrovirus and adventitious viruses such as parvovirus, pseudorabies virus. [44][45][46] It can be used either in flow-through mode or in bind and elute mode, depending on the pI of the antibody and impurities to be removed. For antibodies having a pI above 7.5, which includes most To develop or design a Protein A chromatography operation, several key factors such as flow rate, dimensions of available columns, buffer solution volume, resin cost and processing time need to be considered.…”

Section: Chromatographic Processesmentioning

confidence: 99%

Recovery and purification process development for monoclonal antibody production

Liu

Winter

et al. 2010

mAbs

452

411

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“…Examples of monoliths include polymeric matrices based on poly(glycidyl methacrylate-coethylene dimethacrylate) [13,14], poly(styrene-co-divinylbenzene) [15], poly(acrylamide-co-butyl methacrylate-co-N,N 9-methylenebisacrylamide) [16], as well as on silica [17,18]. At present, monolithic stationary phases have been widely used in the processes of bioseparation (chromatography and electrophoresis) [19,20], bioconversion (enzyme reactors) [21,22], as well as in other processes based on interphase mass distribution (e. g., solid phase peptide synthesis [23,24] and separation of plasmids and viruses [25,26]). …”

Section: Introductionmentioning

confidence: 99%

Preparation of a monolithic column for weak cation exchange chromatography and its application in the separation of biopolymers

Wei¹,

Huang

Liu

et al. 2006

J of Separation Science

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Original PaperPreparation of a monolithic column for weak cation exchange chromatography and its application in the separation of biopolymers A procedure for the preparation of a monolithic column for weak cation exchange chromatography was presented. The structure of the monolithic column was evaluated by mercury intrusion. The hydrodynamic and chromatographic properties of the monolithic column -such as back pressures at different flow rates, effects of pH on protein retention, dynamic loading capacity, recovery, and stability -were determined under conditions typical for ion-exchange chromatography. The prepared monolithic column might be used in a relatively broad pH range from 4.0 to 12.0 and exhibited an excellent separation to five proteins at the flow rates of both 1.0 and 8.0 mL/min, respectively. In addition, the prepared column was first used in the purification and simultaneous renaturation of recombinant human interferon gamma (rhIFN-c) in the extract solution with 7.0 mol/L guanidine hydrochloride. The purity and specific bioactivity of the purified rhIFN-c in only one chromatographic step were obtained to be 93% and 7.8610 7 IU/mg, respectively.

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Impact of multiple re-use of anion-exchange chromatography media on virus removal

Cited by 87 publications

References 33 publications

Understanding the mechanism of virus removal by Q sepharose fast flow chromatography during the purification of CHO‐cell derived biotherapeutics

Understanding the mechanism of virus removal by Q sepharose fast flow chromatography during the purification of CHO‐cell derived biotherapeutics

Recovery and purification process development for monoclonal antibody production

Preparation of a monolithic column for weak cation exchange chromatography and its application in the separation of biopolymers

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