May 6-11, 2018
The biologics industry is changing and all players seek competitiveness through process optimization aiming at satisfying the market demand providing a compliant protein in as short time as possible. As blockbuster drugs experience patent expiry, several biosimilars are coming market and competition becomes fiercer. Unlike classical experiments-based optimization, bioprocess modeling is a rational, economically efficient and reliable alternative to deliver an optimized bioprocess. The biological aspects of a bioreactor are diverse and include cells growing and cycling, other cells dying, nutrients being consumed and by-products accumulating, energy production and usage and therapeutic proteins being produced. The understanding of the biology involved is crucial to ensure quality. Quality by Design (QbD) aspects that can be optimized from the design stages include clone selection, medium formulation, feeding strategies and culture conditions.
In this work, a mathematical model of mammalian cell cultures has been developed. It includes a detailed description of the viable cell population by segregating it according to the stage of the cell cycle (G0/G1, S and G2/M), transition from viable to early and late apoptotic stages. Apoptosis is monitored through gene expression profiles (caspases 3 and 8, bax and bcl-2) linked to the presence or absence of key nutrients. Indeed, the profiles of glucose and 19 amino acids are also captured by the model which allow for detailed information on energy production (ATP) which is essential to ensure viability and hence the delivery of a high-quality product.
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António Lima Grilo and Athanasios Mantalaris, "Towards model-based bioprocess characterization: A mathematical model of cell cycle, metabolism and apoptosis of mAb-producing mammalian cells" in "Cell Culture Engineering XVI", A. Robinson, PhD, Tulane University R. Venkat, PhD, MedImmune E. Schaefer, ScD, J&J Janssen Eds, ECI Symposium Series, (2018). http://dc.engconfintl.org/ccexvi/166