Mathematical modeling as a tool to improve influenza vaccine production processes

Duvigneau, Stefanie; Dürr, Robert; Laske, Tanja; Bachmann, Mandy; Dostert, Melanie; Reichl, Udo; Kienle, Achim

doi:10.1016/j.ifacol.2018.09.004

Cited by 4 publications

(3 citation statements)

References 7 publications

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“…Each state of the single particle description transforms into a coordinate of the corresponding PBE and thus in general high-dimensional multivariate PBEs are obtained. This modeling approach is particularly useful when describing multicellular systems [2,[67][68][69][70][71][72] for which validated models of single cell dynamics are available.…”

Section: Population Balance Modelingmentioning

confidence: 99%

“…The method has been applied successfully for solution of high-dimensional multivariate PBEs of biopolymer- [68,153] and vaccine-production processes [69,70,154]. Recently, application to model-based computer aided screening for optimal genetic modifications in high-yield producer cell lines has been demonstrated [72,155]. An extension to problems involving agglomeration and breakage/cell division has been proposed [71].…”

Section: Dqmom With Efficient Choice Of Abscissasmentioning

confidence: 99%

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Approximate Moment Methods for Population Balance Equations in Particulate and Bioengineering Processes

Dürr

Bück

2020

Processes

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Population balance modeling is an established framework to describe the dynamics of particle populations in disperse phase systems found in a broad field of industrial, civil, and medical applications. The resulting population balance equations account for the dynamics of the number density distribution functions and represent (systems of) partial differential equations which require sophisticated numerical solution techniques due to the general lack of analytical solutions. A specific class of solution algorithms, so-called moment methods, is based on the reduction of complex models to a set of ordinary differential equations characterizing dynamics of integral quantities of the number density distribution function. However, in general, a closed set of moment equations is not found and one has to rely on approximate closure methods. In this contribution, a concise overview of the most prominent approximate moment methods is given.

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Section: Population Balance Modelingmentioning

confidence: 99%

Section: Dqmom With Efficient Choice Of Abscissasmentioning

confidence: 99%

Approximate Moment Methods for Population Balance Equations in Particulate and Bioengineering Processes

Dürr

Bück

2020

Processes

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“…In our contribution, we present a more sophisticated approach, where the random selection of median values is no longer required. To this end, we evaluated four different strategies to generate distributed parameter sets for MGOs based on parameter sets which were estimated from experimental data of their corresponding infected SGOs [6,17]. In the following, the most suitable strategy was used to generate new parameter distributions for potential MGOs to predict the virus yield in model simulations.…”

Section: Introductionmentioning

confidence: 99%

Model-based approach for predicting the impact of genetic modifications on product yield in biopharmaceutical manufacturing—Application to influenza vaccine production

et al. 2020

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A large group of biopharmaceuticals is produced in cell lines. The yield of such products can be increased by genetic engineering of the corresponding cell lines. The prediction of promising genetic modifications by mathematical modeling is a valuable tool to facilitate experimental screening. Besides information on the intracellular kinetics and genetic modifications the mathematical model has to account for ubiquitous cell-to-cell variability. In this contribution, we establish a novel model-based methodology for influenza vaccine production in cell lines with overexpressed genes. The manipulation of the expression level of genes coding for host cell factors relevant for virus replication is achieved by lentiviral transduction. Since lentiviral transduction causes increased cell-to-cell variability due to different copy numbers and integration sites of the gene constructs we use a population balance modeling approach to account for this heterogeneity in terms of intracellular viral components and distributed kinetic parameters. The latter are estimated from experimental data of intracellular viral RNA levels and virus titers of infection experiments using cells overexpressing a single host cell gene. For experiments with cells overexpressing multiple host cell genes, only final virus titers were measured and thus, no direct estimation of the parameter distributions was possible. Instead, we evaluate four different computational strategies to infer these from single gene parameter sets. Finally, the best computational strategy is used to predict the most promising candidates for future modifications that show the highest potential for an increased virus yield in a combinatorial study. As expected, there is a trend to higher yields the more modifications are included.

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Genetic Algorithm-Based Vaccine Optimization Technique to Control COVID-19

Devi

Naved

Gangadevi³

et al. 2022

Lecture Notes on Data Engineering and Communications Technologies

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Mathematical modeling as a tool to improve influenza vaccine production processes

Cited by 4 publications

References 7 publications

Approximate Moment Methods for Population Balance Equations in Particulate and Bioengineering Processes

Approximate Moment Methods for Population Balance Equations in Particulate and Bioengineering Processes

Model-based approach for predicting the impact of genetic modifications on product yield in biopharmaceutical manufacturing—Application to influenza vaccine production

Genetic Algorithm-Based Vaccine Optimization Technique to Control COVID-19

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