Véronique Chotteau
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View article: Cell specific nutrient feeding in perfusion mode enhances hMSC growth in stirred tank bioreactor process
Cell specific nutrient feeding in perfusion mode enhances hMSC growth in stirred tank bioreactor process Open
Human Mesenchymal Stromal Cells (hMSCs) are a safe option for allogeneic cell therapy across various diseases, but their manufacturing process requires improvement to broaden accessibility. In this study, a state-of-the-art planar multi-ve…
View article: Heterogeneity in an adeno-associated virus transfection-based production process limits the production efficiency
Heterogeneity in an adeno-associated virus transfection-based production process limits the production efficiency Open
The popularity of rAAV vectors in gene therapy are placing a burden on current production systems. To improve the accessibility of these life changing treatments, increases in production yields and a reduction in the cost-of-goods are need…
View article: Single-cell transcriptomics reveals dynamics of natural killer cell expansion in a feeder cell-free culture of peripheral blood mononuclear cells—implications for immunotherapy
Single-cell transcriptomics reveals dynamics of natural killer cell expansion in a feeder cell-free culture of peripheral blood mononuclear cells—implications for immunotherapy Open
Natural killer (NK) cell therapies hold great promise for cancer treatment; however, donor-to-donor heterogeneity in the ex vivo expansion process remains a critical bottleneck in their supply. This study aimed to identify factors influenc…
View article: Single-Cell Transcriptomics Reveals Dynamics of NK Cell Expansion in a Feeder Cell-Free Culture of PBMCs - Implications for Immunotherapy
Single-Cell Transcriptomics Reveals Dynamics of NK Cell Expansion in a Feeder Cell-Free Culture of PBMCs - Implications for Immunotherapy Open
Natural killer (NK) cell therapies hold great promise for cancer treatment; however, donor-to-donor heterogeneity in the ex vivo expansion process remains a critical bottleneck in their supply. This study aimed to identify factors influenc…
View article: Macroscopic mechanistic model-based optimization of the feed-medium for mAb yield maximization with CHO-K1 cells under perfusion: a transcriptomics-guided genome-scale approach
Macroscopic mechanistic model-based optimization of the feed-medium for mAb yield maximization with CHO-K1 cells under perfusion: a transcriptomics-guided genome-scale approach Open
We present a novel workow for feed-medium optimization in CHO-K1 perfusion cultures, based on mechanistic macroscopic modeling using Elementary Flux Modes (EFMs). Our approach aims to maximize steady-state monoclonal antibody (mAb) produc…
View article: Data-driven macroscopic kinetic modeling with complex Monod models. Application to CHO-K1 cells with a genome scale metabolic network
Data-driven macroscopic kinetic modeling with complex Monod models. Application to CHO-K1 cells with a genome scale metabolic network Open
Therapeutic proteins from mammalian cells, such as monoclonal antibodies produced by Chinese hamster ovary (CHO) cells, play a critical role in modern medicine. However, the inherent complexity of cellular metabolism poses signicant chall…
View article: Novel Data‐Driven Mechanistic Modeling of Untargeted Metabolome Data Reveals Feed Component Effects in CHO Cell Bioprocess Using Column Generation‐Based EFMs
Novel Data‐Driven Mechanistic Modeling of Untargeted Metabolome Data Reveals Feed Component Effects in CHO Cell Bioprocess Using Column Generation‐Based EFMs Open
This study presents a novel approach for applying mechanistic metabolic modeling to untargeted metabolomics data. The approach was applied to the production process of a difficult‐to‐express enzyme by CHO cells, to identify key feed medium…
View article: Intensification of rAAV Production Based on HEK293 Cell Transient Transfection
Intensification of rAAV Production Based on HEK293 Cell Transient Transfection Open
Recombinant adeno‐associated virus (rAAV) vectors are widely used in gene therapies, but the rapidly increasing global demand has created a significant challenge for rAAV manufacturing, where production capacity remains a critical bottlene…
View article: PAT-on-a-chip: Miniaturization of analytical assays towards data-driven bioprocess development and optimization
PAT-on-a-chip: Miniaturization of analytical assays towards data-driven bioprocess development and optimization Open
The advancement of biopharmaceutical manufacturing, particularly continuous processing, has heightened the need for next-generation analytical tools approaching real-time monitoring of critical quality attributes (CQAs) and process paramet…
View article: Calcium-dependent magnetic separation: A novel approach for the integrated processing of high-quality mAbs
Calcium-dependent magnetic separation: A novel approach for the integrated processing of high-quality mAbs Open
Current monoclonal antibody (mAb) biomanufacturing typically involves expression in mammalian cells during upstream processing (USP), followed by purification during downstream processing (DSP). DSP is a major bottleneck, primarily caused …
View article: Heterogeneity in an Adeno-Associated Virus Transfection-Based Production Process Limits the Production Efficiency
Heterogeneity in an Adeno-Associated Virus Transfection-Based Production Process Limits the Production Efficiency Open
The popularity of rAAV vectors in gene therapy are placing a burden on current production systems. To improve the accessibility of these life changing treatments, increases in production yields and a reduction in the cost-of-goods are need…
View article: Harnessing cell aggregates for enhanced adeno‐associated virus manufacturing: Cultivation strategies and scale‐up considerations
Harnessing cell aggregates for enhanced adeno‐associated virus manufacturing: Cultivation strategies and scale‐up considerations Open
The possibility to produce recombinant adeno‐associated virus (rAAV) by adherent HEK293T cells was studied in a stirred tank bioreactor (STR) culture of cell aggregates. A proof‐of‐concept of rAAV production was successfully demonstrated i…
View article: Side-by-Side Economic Process Model for the Comparison and Evaluation of Magnetic Bead-Based Processes and Legacy Process for the Manufacturing of Monoclonal Antibodies
Side-by-Side Economic Process Model for the Comparison and Evaluation of Magnetic Bead-Based Processes and Legacy Process for the Manufacturing of Monoclonal Antibodies Open
This study models two alternative downstream processes based on magnetic separation with the objective of understanding the economic feasibility of these processes compared to the traditional mAb process. The key focus lies in the economic…
View article: Iterative learning robust optimization - with application to medium optimization of CHO cell cultivation in continuous monoclonal antibody production
Iterative learning robust optimization - with application to medium optimization of CHO cell cultivation in continuous monoclonal antibody production Open
In the presence of uncertainty, the optimum obtained based on a nominal identified model can neither provide any performance guarantee nor ensure that critical constraints are satisfied, which is crucial for e.g., bioprocess applications c…
View article: Data-driven Bayesian estimation of Monod kinetics
Data-driven Bayesian estimation of Monod kinetics Open
In this paper, we consider the well known problem of non-linear identification of the rates of the reactions involved in cells with Monod functions. In bioprocesses, generating data is very expensive and long and so it is important to inco…
View article: Scale‐down of CHO cell cultivation from shake flasks based on oxygen mass transfer allows application of parallelized, non‐invasive, and time‐resolved monitoring of the oxygen transfer rate in 48‐well microtiter plates
Scale‐down of CHO cell cultivation from shake flasks based on oxygen mass transfer allows application of parallelized, non‐invasive, and time‐resolved monitoring of the oxygen transfer rate in 48‐well microtiter plates Open
Cultivating Chinese hamster ovary (CHO) cells in microtiter plates (MTPs) with time‐resolved monitoring of the oxygen transfer rate (OTR) is highly desirable to provide process insights at increased throughput. However, monitoring of the O…
View article: Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments
Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments Open
A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell dens…
View article: Product sieving of <scp>mAb</scp> and its high molecular weight species in different modes of <scp>ATF</scp> and <scp>TFF</scp> perfusion cell cultures
Product sieving of <span>mAb</span> and its high molecular weight species in different modes of <span>ATF</span> and <span>TFF</span> perfusion cell cultures Open
BACKGROUND Tangential flow filtration (TFF) systems are widely used cell retention devices in perfusion cultures, but significant challenges occur with their prolonged operation. A well‐known and common issue includes membrane fouling, whi…
View article: Generic Chemometric Models for Metabolite Concentration Prediction Based on Raman Spectra
Generic Chemometric Models for Metabolite Concentration Prediction Based on Raman Spectra Open
Chemometric models for on-line process monitoring have become well established in pharmaceutical bioprocesses. The main drawback is the required calibration effort and the inflexibility regarding system or process changes. So, a recalibrat…
View article: Enhanced metabolism and negative regulation of ER stress support higher erythropoietin production in HEK293 cells
Enhanced metabolism and negative regulation of ER stress support higher erythropoietin production in HEK293 cells Open
Recombinant protein production can cause severe stress on cellular metabolism, resulting in limited titer and product quality. To investigate cellular and metabolic characteristics associated with these limitations, we compare HEK293 clone…
View article: Integrated continuous biomanufacturing on pilot scale for acid‐sensitive monoclonal antibodies
Integrated continuous biomanufacturing on pilot scale for acid‐sensitive monoclonal antibodies Open
In this study, we demonstrated the first, to our knowledge, integrated continuous bioprocess (ICB) designed for the production of acid‐sensitive monoclonal antibodies, prone to aggregate at low pH, on pilot scale. A high cell density perfu…
View article: Monitoring of amino acids and antibody N-glycosylation in high cell density perfusion culture based on Raman spectroscopy
Monitoring of amino acids and antibody N-glycosylation in high cell density perfusion culture based on Raman spectroscopy Open
Raman spectrum based predictive models provide a process analytical technology (PAT) tool for monitoring and control of culture parameters in bioprocesses. Steady-state perfusion cultures generate a relatively stable metabolite profile, wh…
View article: Capillary and microchip electrophoresis method development for amino acid monitoring during biopharmaceutical cultivation
Capillary and microchip electrophoresis method development for amino acid monitoring during biopharmaceutical cultivation Open
The increased use of biopharmaceuticals calls for improved means of bioprocess monitoring. In this work, capillary electrophoresis (CE) and microchip electrophoresis (MCE) methods were developed and applied for the analysis of amino acids …
View article: Harnessing secretory pathway differences between HEK293 and CHO to rescue production of difficult to express proteins
Harnessing secretory pathway differences between HEK293 and CHO to rescue production of difficult to express proteins Open
Biologics represent the fastest growing group of therapeutics, but many advanced recombinant protein moieties remain difficult to produce. Here, we identify metabolic engineering targets limiting expression of recombinant human proteins th…
View article: Proof-of-Concept of a Novel Cell Separation Technology Using Magnetic Agarose-Based Beads
Proof-of-Concept of a Novel Cell Separation Technology Using Magnetic Agarose-Based Beads Open
The safety of the cells used for Advanced Therapy Medicinal Products is crucial for patients. Reliable methods for the cell purification are very important for the commercialization of those new therapies. With the large production scale e…
View article: Proof-of-Concept of Continuous Transfection for Adeno-Associated Virus Production in Microcarrier-Based Culture
Proof-of-Concept of Continuous Transfection for Adeno-Associated Virus Production in Microcarrier-Based Culture Open
Adeno-associated virus vectors (AAV) are reported to have a great potential for gene therapy, however, a major bottleneck for this kind of therapy is the limitation of production capacity. Higher specific AAV vector yield is often reported…
View article: Autophagy and intracellular product degradation genes identified by systems biology analysis reduce aggregation of bispecific antibody in CHO cells
Autophagy and intracellular product degradation genes identified by systems biology analysis reduce aggregation of bispecific antibody in CHO cells Open
Aggregation of therapeutic bispecific antibodies negatively affects the yield, shelf-life, efficacy and safety of these products. Pairs of stable Chinese hamster ovary (CHO) cell lines produced two difficult-to-express bispecific antibodie…
View article: Robust optimization with optimal experiment design - with application to continuous biopharmaceutical production
Robust optimization with optimal experiment design - with application to continuous biopharmaceutical production Open
Model-based optimization typically obtains the optimum based on a nominal identified model. However, in the presence of uncertainty, the nominal optimum leads to suboptimal operating conditions that furthermore can be highly sensitive to u…