Laetitia Malphettes

Learn More
IgG1 antibodies produced in Chinese hamster ovary (CHO) cells are heavily alpha1,6-fucosylated, a modification that reduces antibody-dependent cellular cytotoxicity (ADCC) and can inhibit therapeutic antibody function in vivo. Addition of fucose is catalyzed by Fut8, a alpha1,6-fucosyltransferase. FUT8(-/-) CHO cell lines produce completely nonfucosylated(More)
Abstract We review major modeling strategies and methods to understand and simulate the macroscopic behavior of mammalian cells. These strategies comprise two important steps: the first step is to identify stoichiometric relationships for the cultured cells connecting the extracellular inputs and outputs. In a second step, macroscopic kinetic models are(More)
Background Mammalian cells are used extensively in the production of recombinant proteins, and of monoclonal antibodies (MAbs) in particular. The trend towards avoiding animal-derived components in biopharmaceutical production processes has led to the extensive use of nonanimal origin hydrolysates such as plant hydrolysates or yeast hydrolysates. The source(More)
Background The goal of manufacturing process development for drug substance and drug product is to establish a commercial process capable of consistently producing drug substance/drug product of the intended quality. Based on regulatory requirements, the manufacturing process has to be characterized prior to process validation. Since performing the(More)
Background Enhancing throughput of bioprocess development has become increasingly important to rapidly screen and optimize cell culture process parameters. With increasing timeline pressures to get therapeutic candidates into the clinic, resource intensive approaches such as the use of shake flasks and bench-top bioreactors may limit the design space for(More)
Background Current trend towards Quality by Design (QbD) leads the process development exercise towards systematic experimentation, rational development, process understanding, characterization and control. In this study, an example of the application of QbD approach is given. Optimization of the feeding strategy and the target seeding density was performed(More)
Background In the biopharmaceutical industry, process development and optimization is key to produce high quality recombinant proteins at high yields. As technologies mature, pressure on cost and timelines becomes greater for delivering scalable and robust processes. Overall, process development should be viewed as a continuum from the early stages up to(More)
We describe a systematic approach to model CHO metabolism during biopharmaceutical production across a wide range of cell culture conditions. To this end, we applied the metabolic steady state concept. We analyzed and modeled the production rates of metabolites as a function of the specific growth rate. First, the total number of metabolic steady state(More)
Background It has always been an objective of process development and more recently it has also become a regulatory expectation to build robustness into and demonstrate proper control of a manufacturing process, thus ensuring that the biological product meets consistently its quality attributes and specifications. This is achieved mainly through systematic(More)
Introduction Bio-pharmaceutical industries face an increasing demand to accelerate process development and reduce costs. This challenge requires high throughput tools to replace the traditional combination of shake flasks and small-scale stirred tank bioreactors. A conventional and widely used process development tool is the stirred tank reactor (STR)(More)