Modeling and simulation of anion-exchange membrane chromatography for purification of Sf9 insect cell-derived virus-like particles

Effio, Christopher Ladd; Hahn, Tobias; Seiler, Julia; Oelmeier, Stefan A.; Asen, Iris; Silberer, Christine; Villain, Louis; Hubbuch, Jürgen

doi:10.1016/j.chroma.2015.12.006

Cited by 36 publications

(17 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bind and elute chromatography, the work horse in biopharmaceutical manufacturing for capture, purification, and polishing, suffers from low dynamic binding capacities ( Ladd Effio and Hubbuch, 2015 ), diffusion limitations ( Kramberger et al, 2015 ), and often too small pore sizes ( Kattur Venkatachalam et al, 2014 ) for the purification of VLPs. Size differences between VLPs and the bulk of host cell contaminants can be exploited by size-sensitive techniques such as size-exclusion chromatography (SEC) – especially for analytical purposes ( Ladd Effio et al, 2016 ) – precipitation, filtration, and ultracentrifugation ( Ladd Effio and Hubbuch, 2015 ). While ultracentrifugation is applied to lab-scale processes ( Jiang et al, 1992 ; Mason et al, 1996 ; Ausar et al, 2006 ), scalability and variability issues, among others, hamper its application to industrial-scale processes ( Koho et al, 2012 ; Kleiner et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Integrated Process for Capture and Purification of Virus-Like Particles: Enhancing Process Performance by Cross-Flow Filtration

Hillebrandt

Vormittag

Bluthardt

et al. 2020

Front. Bioeng. Biotechnol.

Self Cite

View full text Add to dashboard Cite

Virus-like particles (VLPs) are emerging nanoscale protein assemblies applied as prophylactic vaccines and in development as therapeutic vaccines or cargo delivery systems. Downstream processing (DSP) of VLPs comes both with challenges and opportunities, depending on the complexity and size of the structures. Filtration, precipitation/re-dissolution and size-exclusion chromatography (SEC) are potent technologies exploiting the size difference between product and impurities. In this study, we therefore investigated the integration of these technologies within a single unit operation, resulting in three different processes, one of which integrates all three technologies. VLPs, contained in clarified lysate from Escherichia coli, were precipitated by ammonium sulfate, washed, and re-dissolved in a commercial cross-flow filtration (CFF) unit. Processes were analyzed for yield, purity, as well as productivity and were found to be largely superior to a reference centrifugation process. Productivity was increased 2.6-fold by transfer of the wash and re-dissolution process to the CFF unit. Installation of a multimodal SEC column in the permeate line increased purity to 96% while maintaining a high productivity and high yield of 86%. In addition to these advantages, CFF-based capture and purification allows for scalable and disposable DSP. In summary, the developed setup resulted in high yields and purities, bearing the potential to be applied as an integrated process step for capture and purification of in vivo-assembled VLPs and other protein nanoparticles.

show abstract

Section: Introductionmentioning

confidence: 99%

Integrated Process for Capture and Purification of Virus-Like Particles: Enhancing Process Performance by Cross-Flow Filtration

Hillebrandt

Vormittag

Bluthardt

et al. 2020

Front. Bioeng. Biotechnol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The description of the binding behavior was commonly performed using an adsorption isotherm model. Many different examples can be found in the literature, such as the steric mass action or the Langmuir isotherm [ 26 , 51 ]. For hydrogel grafted ion-exchange media, the Langmuir isotherm model has been proven to sufficiently describe the observed adsorption behavior.…”

Section: Resultsmentioning

confidence: 99%

“…Modeling of hydrogel grafted chromatographic media with no internal porosity, especially membrane adsorbers, has been previously performed by several researchers [ 24 , 26 , 28 ]. In general, the chromatographic process is understood as a physical mechanism of mass-transport via convection and axial dispersion in the mobile phase.…”

Section: Theoreticalmentioning

confidence: 99%

“…As demonstrated in numerous studies, the analysis and modeling of mass-transfer mechanisms and kinetic phenomena involved during chromatographic operations is an important tool regarding scale-up purposes [ 14 ], quality-by-design approaches [ 15 , 16 ], as well as process integration and optimization [ 17 ]. This approach has been proven to be effective for conventional resin based media [ 18 , 19 , 20 , 21 , 22 ] as well as for membrane adsorbers [ 23 , 24 , 25 , 26 ]. Numerous mathematical models have been proposed to describe the profiles obtained during chromatographic operations, characterized by different complexity levels in the description of the relevant mass-transport phenomena [ 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Purification of Monoclonal Antibodies Using a Fiber Based Cation-Exchange Stationary Phase: Parameter Determination and Modeling

et al. 2016

Self Cite

View full text Add to dashboard Cite

Monoclonal antibodies (mAb) currently dominate the market for protein therapeutics. Because chromatography unit operations are critical for the purification of therapeutic proteins, the process integration of novel chromatographic stationary phases, driven by the demand for more economic process schemes, is a field of ongoing research. Within this study it was demonstrated that the description and prediction of mAb purification on a novel fiber based cation-exchange stationary phase can be achieved using a physico-chemical model. All relevant mass-transport phenomena during a bind and elute chromatographic cycle, namely convection, axial dispersion, boundary layer mass-transfer, and the salt dependent binding behavior in the fiber bed were described. This work highlights the combination of model adaption, simulation, and experimental parameter determination through separate measurements, correlations, or geometric considerations, independent from the chromatographic cycle. The salt dependent binding behavior of a purified mAb was determined by the measurement of adsorption isotherms using batch adsorption experiments. Utilizing a combination of size exclusion and protein A chromatography as analytic techniques, this approach can be extended to a cell culture broth, describing the salt dependent binding behavior of multiple components. Model testing and validation was performed with experimental bind and elute cycles using purified mAb as well as a clarified cell culture broth. A comparison between model calculations and experimental data showed a good agreement. The influence of the model parameters is discussed in detail.

show abstract

“…It covers fluid convection, axial dispersion of the fluid, as well as internal and external mass transport phenomena . The GRM was employed for modeling the IEX separation of BSA and IgG as well as for extracting B19 parvovirus‐like particles from an Sf9 insect cell broth using a hydrogel‐crafted AEX membrane . The transport‐dispersive model is a simplification of the GRM as film and pore diffusion is combined in a lumped effective mass transfer coefficient.…”

Section: Modeling Approachesmentioning

confidence: 99%

Downstream process development strategies for effective bioprocesses: Trends, progress, and combinatorial approaches

Baumann

Hubbuch

2016

Engineering in Life Sciences

Self Cite

View full text Add to dashboard Cite

The biopharmaceutical industry is at a turning point moving toward a more customized and patient-oriented medicine (precision medicine). Straightforward routines such as the antibody platform process are extended to production processes for a new portfolio of molecules. As a consequence, individual and tailored productions require generic approaches for a fast and dedicated purification process development. In this article, different effective strategies in biopharmaceutical purification process development are reviewed that can analogously be used for the new generation of antibodies. Conventional approaches based on heuristics and high-throughput process development are discussed and compared to modern technologies such as multivariate calibration and mechanistic modeling tools. Such approaches constitute a good foundation for fast and effective process development for new products and processes, but their full potential becomes obvious in a correlated combination. Thus, different combinatorial approaches are presented, which might become future directions in the biopharmaceutical industry.

show abstract

Modeling and simulation of anion-exchange membrane chromatography for purification of Sf9 insect cell-derived virus-like particles

Cited by 36 publications

References 50 publications

Integrated Process for Capture and Purification of Virus-Like Particles: Enhancing Process Performance by Cross-Flow Filtration

Integrated Process for Capture and Purification of Virus-Like Particles: Enhancing Process Performance by Cross-Flow Filtration

Purification of Monoclonal Antibodies Using a Fiber Based Cation-Exchange Stationary Phase: Parameter Determination and Modeling

Downstream process development strategies for effective bioprocesses: Trends, progress, and combinatorial approaches

Contact Info

Product

Resources

About