See below

Lead Research Organisation: University College London
Department Name: Biochemical Engineering

Abstract

Full title: A framework for the development, analysis and validation of mathematical models of upstream unit operations used in the production of recombinant proteins as part of an integrated whole bioprocess modelling platform

Summary: The development of predictive and robust mathematical models enables the application of traditional process systems engineering (PSE) techniques (such as model-based optimization) to cell-based bioprocesses leading to increased productivity and reduced operating costs (Kiparissides et al, 2015). However, despite recent advances in modelling tools in the areas of systems biology and metabolic engineering, several challenges still remain before detailed kinetic models reach the degree of maturity required for conventional use in industrial applications (Almquist et al, 2014). The aim of this project is to bridge this apparent 'information gap' by developing a novel computational approach able to integrate, organize and guide experimental information across multiple scales and unit operations in order to enable 'whole bioprocess' simulation and optimization studies. The developed models will be experimentally validated and will be used to derive optimal fed-batch feeding strategies (through model based optimization) and, subsequently, to implement these strategies at the bioreactor scale (through automated model predictive control). The EngD researcher will utilise the gPROMS family of products for the development of mathematical models and will focus on their 'plug-and-play' integration within PSE's whole bioprocess modelling platform.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R512400/1 01/10/2017 31/03/2022
1930924 Studentship EP/R512400/1 25/09/2017 24/12/2021 Viktoria Gkoutzioupa
 
Description Monoclonal antibodies (mAbs) are therapeutical proteins which are widely used for the production of biopharmaceuticals. Chinese hamster ovary (CHO) cells are the main hosts for the production of these proteins. The project aims in the development of a mathematical model that would predict the behaviour of CHO cells, as well as the production of mAbs, in different scales (bioreactors and shake flasks) and operating conditions. The project also investigates the effect of the quality of the upstream culture broth on the downstream processing with a focus in primary clarification. A number of critical quality attributes is analysed. Analysis tools, such as Design of Experiments (DoE) are used for the interpretation of the experimental results. These experimental results are also used for the calibration and validation of the model.
Exploitation Route The project is both computational and experimental, so the outcomes can be relevant in various sectors. Firstly, the project is in collaroration with Process Systems Enterprise Ltd (PSE). PSE is a leading software company that focuses in industrial process modelling with a prominent interest in biopharmaceutical sector. The model that is being developed, under the current award, can be part of PSE's modelling libraries, which will be eventually used by its clients, i.e biopharma companies. Biopharma companies are interested in modelling applications because they can have a better understanding of the process, prediction of the system behavior and severe reduction of the number of screening experiments that are required for product developement. Additionally, the outcomes that are related to the experiments of this award can be utilised by pharma industry for the optimisation of the upstream and downstream processing through the better understanding of the cell metabolism.
Sectors Digital/Communication/Information Technologies (including Software),Pharmaceuticals and Medical Biotechnology

 
Description My project is in collaboration with Process Systems Enterprise (PSE) which is a software company based in London. As part of this collaboration, I share data from my experiments with them, which are subsequently used for the development of their modelling libraries. Additionally, kinetic models that I have developed during my PhD are also used in their software.
First Year Of Impact 2019
Sector Digital/Communication/Information Technologies (including Software)
Impact Types Economic

 
Description A framework for the development, analysis and validation of mathematical models of upstream unit operations used in the production of recombinant proteins as part of an integrated whole bioprocess modelling platform 
Organisation Process Systems Enterprise Limited (PSE)
Country United Kingdom 
Sector Private 
PI Contribution We provide experimental data and develop the kinetic models
Collaborator Contribution They provide the software as well as support for the model development and the model implementation into the software
Impact The outcomes so far involve the development of kinetic equations that describe the behavior of some of the variables of the system and also analysis of the model robustness with sensitivity analysis.
Start Year 2017