Conference Summary: Gaps, Lessons Learned, and Areas for Improvement

Brorson, Kurt; Miesegaes, George; Tounekti, Omar; Skene, Judy; Blümel, Johannes

doi:10.5731/pdajpst.2014.00968

Cited by 4 publications

(4 citation statements)

References 5 publications

(2 reference statements)

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“…These interactions appear to have electrostatic, hydrophobic or hydrogen bonding components (Bach & Connell-Crowley, 2015). This study advanced the understanding of the mechanism of XMuLV removal on protein A but the applicability to other model viruses and protein A resins has yet to be studied (Brorson, Miesegaes, Tounekti, Skene, & Blumel, 2014).…”

Section: Introductionmentioning

confidence: 93%

“…Bach and Connell-Crowley (2015) studied the behavior of XMuLV on an agarose-base-matrix protein A resin, and their findings indicate that XMuLV has some interaction with the resin backbone and ligand, and also appears to bind to and coelute with the mAb. This study advanced the understanding of the mechanism of XMuLV removal on protein A but the applicability to other model viruses and protein A resins has yet to be studied (Brorson, Miesegaes, Tounekti, Skene, & Blumel, 2014). This study advanced the understanding of the mechanism of XMuLV removal on protein A but the applicability to other model viruses and protein A resins has yet to be studied (Brorson, Miesegaes, Tounekti, Skene, & Blumel, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Characterizing and enhancing virus removal by protein A chromatography

Pan¹,

Becerra-Arteaga

Tran³

et al. 2019

Biotech & Bioengineering

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Protein A chromatography is an effective capture step to separate Fc-containing biopharmaceuticals from cell culture impurities but is generally not effective for virus removal, which tends to vary among different products. Previous findings have pointed to the differences in feedstocks to protein A, composed of the products and other cell culture-related impurities. To separate the effect of the feedstock components on virus removal, and understand why certain monoclonal antibody (mAb) products have low virus log reduction values (LRVs) across protein A chromatography, we investigated the partitioning of three types of viruses on Eshmuno® A columns. Using pure mAbs, we found that low LRVs were correlated with the presence of the particular mAb product itself, causing altered partitioning patterns. Three virus types were tested, and the trend in partitioning was the same for retrovirus-like particles (RVLPs) expressed in the cell substrate, and its model virus xenotropic murine leukemia virus (XMuLV), whereas slightly different for murine minute virus. These results were extended from previous observation described by Bach and Connell-Crowley (2015) studying XMuLV partitioning on MabSelect SuRe columns, providing further evidence using additional types of viruses and resin. Other product-specific cell culture impurities in harvested cell culture fluid played a lesser role in causing low LRVs. In addition, using high throughput screening (HTS) methods and Eshmuno® A resin plates, we identified excipients with ionic and hydrophobic properties that could potentially alleviate the mAb-induced LRV reduction, indicating that both ionic and hydrophobic interactions were involved. More excipients of such nature or combinations, once optimized, can potentially be used as load and/or wash additives to improve virus removal by protein A. We have demonstrated that HTS is a valuable tool for this type of screening, whether to gain deeper understanding of a mechanism, or to provide guidance during the optimization of protein A process with improved virus removal. K E Y W O R D S Chinese Hamster Ovary cells, Eshmuno ® A, high throughput screening (HTS), protein A chromatography, virus removal Biotechnology and Bioengineering. 2019;116:846-856. wileyonlinelibrary.com/journal/bit 846 | Abbreviations: CHO, Chinese Hamster Ovary; RVLP, retrovirus-like particles; HTS, high throughput screening; XMuLV, xenotropic murine leukemia virus; MMV, murine minute virus;RT-QPCR, real-time quantitative PCR; LRV, log reduction value. *Pan and Becerra-Arteaga have contributed equally to this study.

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Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Characterizing and enhancing virus removal by protein A chromatography

Pan¹,

Becerra-Arteaga

Tran³

et al. 2019

Biotech & Bioengineering

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“…The presumed failure mechanism for noncatastrophic failures is particle diffusion, where it is hypothesized that virus migrates through the membrane structure during flow disruptions by diffusion (Bohonak & Zydney, 2005; Dishari et al, 2015; Fallahianbijan et al, 2017). Operating conditions that are considered worst‐case (e.g., increase particle diffusion) include low transmembrane pressure, transitions in pressure, low flux, or pausing of pressure/flow (Brorson et al, 2014; Fan et al, 2021; LaCasse et al, 2016; Strauss et al, 2017). In general, previous generation virus filters suffered a decline in viral retention at lower pressures or with flow pauses (Fan et al, 2021; LaCasse et al, 2016), and log reduction values (LRVs) of MMV varied depending on the product and feed solution conditions (Strauss et al, 2017).…”

Section: Integrity Testingmentioning

confidence: 99%

Virus filtration: A review of current and future practices in bioprocessing

Johnson¹,

Chen

Bolton

et al. 2022

Biotech & Bioengineering

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For drug products manufactured in mammalian cells, safety assurance practices are needed during production to assure that the final medicinal product is safe from the potential risk of viral contamination. Virus filters provide viral retention for a range of viruses through robust, largely size-based retention mechanism.Therefore, a virus filtration step is commonly utilized in a well-designed recombinant therapeutic protein purification process and is a key component in an overall strategy to minimize the risks of adventitious and endogenous viral particles during the manufacturing of biotechnology products. This study summarizes the history of virus filtration, currently available virus filters and prefilters, and virus filtration integrity test methods and study models. There is also discussion of current understanding and gaps with an eye toward future trends and emerging filtration technologies.

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“…Bell reported on the first US FDA approved viral clearance design space [54]. In general, Brorson et al [55] recommend that one factor in successful acceptance of using a quality-by-design approach for virus clearance is to proactively raise the issue with the regulators.…”

Section: Innovations and Opportunities In Viral Clearance And Virus Safetmentioning

confidence: 99%

Viral clearance for biopharmaceutical downstream processes

Shukla¹,

Aranha²

2015

Pharmaceutical Bioprocessing

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Viral clearance studies are mandated prior to entering clinical trials and for commercial launch of biopharmaceuticals. These studies are a key component of risk mitigation to reduce the potential for iatrogenic transmission of pathogenic viruses. This paper reviews regulatory guidance and practical strategies for designing viral clearance studies. Essential elements of a developmental phase-appropriate viral clearance package are detailed. These include scale-down model qualification, virus spike experiments and validation (clearance evaluation) of manufacturing process steps. Heuristics and learnings from available data are shared. Developments in this area including generic validation strategies, multiviral spiking strategies and use of newer model viruses for nonconventional substrates are also described. This review provides a framework for a comprehensive viral validation package for regulatory submissions.

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Conference Summary: Gaps, Lessons Learned, and Areas for Improvement

Cited by 4 publications

References 5 publications

Characterizing and enhancing virus removal by protein A chromatography

Characterizing and enhancing virus removal by protein A chromatography

Virus filtration: A review of current and future practices in bioprocessing

Viral clearance for biopharmaceutical downstream processes

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