Imperial College London

Dr Cleo Kontoravdi

Faculty of EngineeringDepartment of Chemical Engineering

Reader in Biosystems Engineering
 
 
 
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Contact

 

+44 (0)20 7594 6655cleo.kontoravdi98 Website

 
 
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Location

 

516ACE ExtensionSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
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77 results found

Goey CH, Bell D, Kontoravdi C, 2019, CHO cell cultures in shake flasks and bioreactors present different host cell protein profiles in the supernatant, BIOCHEMICAL ENGINEERING JOURNAL, Vol: 144, Pages: 185-192, ISSN: 1369-703X

JOURNAL ARTICLE

Kotidis P, Kontoravdi C, Strategic Framework for Parameterization of Cell Culture Models, Processes, Vol: 7, Pages: 174-174

<jats:p>Global Sensitivity Analysis (GSA) is a technique that numerically evaluates the significance of model parameters with the aim of reducing the number of parameters that need to be estimated accurately from experimental data. In the work presented herein, we explore different methods and criteria in the sensitivity analysis of a recently developed mathematical model to describe Chinese hamster ovary (CHO) cell metabolism in order to establish a strategic, transferable framework for parameterizing mechanistic cell culture models. For that reason, several types of GSA employing different sampling methods (Sobol’, Pseudo-random and Scrambled-Sobol’), parameter deviations (10%, 30% and 50%) and sensitivity index significance thresholds (0.05, 0.1 and 0.2) were examined. The results were evaluated according to the goodness of fit between the simulation results and experimental data from fed-batch CHO cell cultures. Then, the predictive capability of the model was tested against four different feeding experiments. Parameter value deviation levels proved not to have a significant effect on the results of the sensitivity analysis, while the Sobol’ and Scrambled-Sobol’ sampling methods and a 0.1 significance threshold were found to be the optimum settings. The resulting framework was finally used to calibrate the model for another CHO cell line, resulting in a good overall fit. The results of this work set the basis for the use of a single mechanistic metabolic model that can be easily adapted through the proposed sensitivity analysis method to the behavior of different cell lines and therefore minimize the experimental cost of model development.</jats:p>

JOURNAL ARTICLE

Kotidis P, Demis P, Goey CH, Correa E, McIntosh C, Trepekli S, Shah N, Klymenko OV, Kontoravdi Cet al., 2019, Constrained global sensitivity analysis for bioprocess design space identification, Computers & Chemical Engineering, ISSN: 0098-1354

JOURNAL ARTICLE

Kotidis P, Jedrzejewski P, Sou SN, Sellick C, Polizzi K, Del Val IJ, Kontoravdi Cet al., 2019, Model-based optimization of antibody galactosylation in CHO cell culture., Biotechnol Bioeng

Exerting control over the glycan moieties of antibody therapeutics is highly desirable from a product safety and batch-to-batch consistency perspective. Strategies to improve antibody productivity may compromise quality, while interventions for improving glycoform distribution can adversely affect cell growth and productivity. Process design therefore needs to consider the trade-off between preserving cellular health and productivity while enhancing antibody quality. In this work, we present a modeling platform that quantifies the impact of glycosylation precursor feeding - specifically that of galactose and uridine - on cellular growth, metabolism as well as antibody productivity and glycoform distribution. The platform has been parameterized using an initial training data set yielding an accuracy of ±5% with respect to glycoform distribution. It was then used to design an optimized feeding strategy that enhances the final concentration of galactosylated antibody in the supernatant by over 90% compared with the control without compromising the integral of viable cell density or final antibody titer. This work supports the implementation of Quality by Design towards higher-performing bioprocesses.

JOURNAL ARTICLE

Kis Z, Shattock R, Shah N, Kontoravdi Cet al., 2019, Emerging Technologies for Low-Cost, Rapid Vaccine Manufacture, BIOTECHNOLOGY JOURNAL, Vol: 14, ISSN: 1860-6768

JOURNAL ARTICLE

Kontoravdi C, del Val IJ, 2018, Computational tools for predicting and controlling the glycosylation of biopharmaceuticals, CURRENT OPINION IN CHEMICAL ENGINEERING, Vol: 22, Pages: 89-97, ISSN: 2211-3398

JOURNAL ARTICLE

Goey CH, Alhuthali S, Kontoravdi C, 2018, Host cell protein removal from biopharmaceutical preparations: Towards the implementation of quality by design, BIOTECHNOLOGY ADVANCES, Vol: 36, Pages: 1223-1237, ISSN: 0734-9750

JOURNAL ARTICLE

Sou SN, Lee K, Nayyar K, Polizzi KM, Sellick C, Kontoravdi Cet al., 2018, Exploring cellular behavior under transient gene expression and its impact on mAb productivity and Fc-glycosylation, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 115, Pages: 512-518, ISSN: 0006-3592

JOURNAL ARTICLE

Heide C, Ces O, Polizzi KM, Kontoravdi Cet al., 2018, Creating cell-free protein synthesis factories, PHARMACEUTICAL BIOPROCESSING, Vol: 6, Pages: 3-6, ISSN: 2048-9145

JOURNAL ARTICLE

Goey CH, Bell D, Kontoravdi C, 2018, Mild hypothermic culture conditions affect residual host cell protein composition post-Protein A chromatography, MABS, Vol: 10, Pages: 476-487, ISSN: 1942-0862

JOURNAL ARTICLE

Goey CH, Tsang JMH, Bell D, Kontoravdi Cet al., 2017, Cascading effect in bioprocessing-The impact of mild hypothermia on CHO cell behavior and host cell protein composition, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 114, Pages: 2771-2781, ISSN: 0006-3592

JOURNAL ARTICLE

Cardenas-Fernandez M, Bawn M, Hamley-Bennett C, Bharat PKV, Subrizi F, Suhaili N, Ward DP, Bourdin S, Dalby PA, Hailes HC, Hewitson P, Ignatova S, Kontoravdi C, Leak DJ, Shah N, Sheppard TD, Ward JM, Lye GJet al., 2017, An integrated biorefinery concept for conversion of sugar beet pulp into value-added chemicals and pharmaceutical intermediates, FARADAY DISCUSSIONS, Vol: 202, Pages: 415-431, ISSN: 1359-6640

JOURNAL ARTICLE

Sou SN, Jedrzejewski PM, Lee K, Sellick C, Polizzi KM, Kontoravdi Cet al., 2017, Model-based investigation of intracellular processes determining antibody Fc-glycosylation under mild hypothermia, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 114, Pages: 1570-1582, ISSN: 0006-3592

JOURNAL ARTICLE

Goers L, Ainsworth C, Goey CH, Kontoravdi C, Freemont PS, Polizzi KMet al., 2017, Whole-cell Escherichia coli lactate biosensor for monitoring mammalian cell cultures during biopharmaceutical production, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 114, Pages: 1290-1300, ISSN: 0006-3592

JOURNAL ARTICLE

Goers L, Ainsworth C, Goey CH, Kontoravdi C, Freemont PS, Polizzi KMet al., 2017, Cover Image, Volume 114, Number 6, June 2017.

Cover Legend The cover image, by Lisa Goers et al., is based on the Article Whole-cell Escherichia coli lactate biosensor for monitoring mammalian cell cultures during biopharmaceutical production, DOI: 10.1002/bit.26254.

OTHER

Alhuthali S, Fadda S, Gocy CH, Kontoravdi Cet al., 2017, Multi-stage population balance model to understand the dynamics of fed-batch CHO cell culture, 27th European Symposium on Computer-Aided Process Engineering (ESCAPE), Publisher: ELSEVIER SCIENCE BV, Pages: 2821-2826, ISSN: 1570-7946

CONFERENCE PAPER

Klymenko OV, Shah N, Kontoravdi C, Royle KE, Polizzi KMet al., 2016, Designing an Artificial Golgi Reactor to Achieve Targeted Glycosylation of Monoclonal Antibodies, AICHE JOURNAL, Vol: 62, Pages: 2959-2973, ISSN: 0001-1541

JOURNAL ARTICLE

del Val IJ, Polizzi KM, Kontoravdi C, 2016, A theoretical estimate for nucleotide sugar demand towards Chinese Hamster Ovary cellular glycosylation, SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322

JOURNAL ARTICLE

Polizzi KM, Kontoravdi C, 2016, Vaccine production, ISBN: 9781439803332

BOOK

Niu H, Shah N, Kontoravdi C, 2016, Modelling of amorphous cellulose depolymerisation by cellulases, parametric studies and optimisation, BIOCHEMICAL ENGINEERING JOURNAL, Vol: 105, Pages: 455-472, ISSN: 1369-703X

JOURNAL ARTICLE

Fan Y, Del Val IJ, Muller C, Lund AM, Sen JW, Rasmussen SK, Kontoravdi C, Baycin-Hizal D, Betenbaugh MJ, Weilguny D, Andersen MRet al., 2015, A multi-pronged investigation into the effect of glucose starvation and culture duration on fed-batch CHO cell culture, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 112, Pages: 2172-2184, ISSN: 0006-3592

JOURNAL ARTICLE

Sou SN, Sellick C, Lee K, Mason A, Kyriakopoulos S, Polizzi KM, Kontoravdi Cet al., 2015, How does mild hypothermia affect monoclonal antibody glycosylation?, Biotechnology and Bioengineering, Vol: 112, Pages: 1165-1176, ISSN: 1097-0290

JOURNAL ARTICLE

Fan Y, Del Val IJ, Mueller C, Sen JW, Rasmussen SK, Kontoravdi C, Weilguny D, Andersen MRet al., 2015, Amino Acid and Glucose Metabolism in Fed-Batch CHO Cell Culture Affects Antibody Production and Glycosylation, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 112, Pages: 521-535, ISSN: 0006-3592

JOURNAL ARTICLE

Polizzi KM, Kontoravdi C, 2015, Genetically-encoded biosensors for monitoring cellular stress in bioprocessing, CURRENT OPINION IN BIOTECHNOLOGY, Vol: 31, Pages: 50-56, ISSN: 0958-1669

JOURNAL ARTICLE

Niv H, Leak D, Shah N, Kontoravdi Cet al., 2015, Metabolic characterization and modeling of fermentation process of an engineered Geobacillus thermoglucosidasius strain for bioethanol production with gas stripping, CHEMICAL ENGINEERING SCIENCE, Vol: 122, Pages: 138-149, ISSN: 0009-2509

JOURNAL ARTICLE

Oliveira PH, Mairhofer J, Alves PM, Lara AR, Kontoravdi Cet al., 2015, Advances in the Development of Biotherapeutics, BioMed Research International, Vol: 2015, ISSN: 2314-6133

JOURNAL ARTICLE

Kyriakopoulos S, Kontoravdi C, 2014, A Framework for the Systematic Design of Fed-Batch Strategies in Mammalian Cell Culture, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 111, Pages: 2466-2476, ISSN: 0006-3592

JOURNAL ARTICLE

Kyriakopoulos S, Kontoravdi C, 2014, Insights on biomarkers from Chinese hamster ovary ‘omics’ studies, Pharmaceutical Bioprocessing, Vol: 2, Pages: 389-401, ISSN: 2048-9145

JOURNAL ARTICLE

Todri E, Amenaghawon AN, del Val IJ, Leak DJ, Kontoravdi C, Kucherenko S, Shah Net al., 2014, Global sensitivity analysis and meta-modeling of an ethanol production process, CHEMICAL ENGINEERING SCIENCE, Vol: 114, Pages: 114-127, ISSN: 0009-2509

JOURNAL ARTICLE

Jedrzejewski PM, del Val IJ, Constantinou A, Dell A, Haslam SM, Polizzi KM, Kontoravdi Cet al., 2014, Towards Controlling the Glycoform: A Model Framework Linking Extracellular Metabolites to Antibody Glycosylation, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 15, Pages: 4492-4522, ISSN: 1422-0067

JOURNAL ARTICLE

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