(366p) Somesh Mishra, Cabbi, Darpa, University of Illinois Urbana-Champaign (UIUC), IL, Usapostdoc Research Associate at Uiuc

Much of current research is driven toward sustainability through precision fermentation for manufacturing food-analogous. The second wave of synthetic biology enables the faster manufacturing of sustainable products (food, proteins, and chemicals). The invented expression system is often conceptually viewed as optimum. However, before ascertaining its commercial potential, there is a need to identify KPPs for process optimization, cost reduction, and DSP . The factors affecting and are not limited to growth media, cell density control, temperature, and agitation. Usually, the cellular media applied during cell line establishment studies is loaded with various supplements, growth factors, and antibiotics, which are unsuitable for commercialization and forbidden for regulatory reasons. To avoid this media development studies for commercially viable titer and product yield is required. Likewise, identifying KPPs (pH, temperature, agitation, aeration, DO), and fermentation mode at the lab scale that could influence the product titer, yield, quality, purity, and stability, and analytics is crucial for scale-up, DSP, and economics. Looping lab and pre-commercial scale for testing, learning, improving, and validating (TLIV) is essential to achieve the desired outcome.

I, therefore, propose a rationalized, unified, multidimensional approach to meet the goal of commercially viable precision fermentation involving (i) growth media selection, decision on titer, yield, and productivity on inputs of economics; (ii) applying experiments based on statistical approaches to identify and optimize fermentation KPPs, in parallel development of DSP. The DSP information is applied to improve fermentation (feedback approach for better product quality at reduced cost); (iii) apply TLIV between lab and pre-commercial scale. All the results will be supported and interpreted utilizing hybrid modeling approaches.

Selected Publications:

VG Tran, S Mishra, SS Bhagwat et al., 2023. An end-to-end pipeline for succinic acid production at an industrially relevant scale using Issatchenkia orientalis. Nature Communications 14 (1), 6152

S Mishra, V Kumar, J Sarkar, AS Rathore. 2021. CFD-based mass transfer modeling of a single-use bioreactor for production of monoclonal antibody biotherapeutics. Chemical Engineering Journal 267, 118323

S Mishra, A S.Rathore, N Saxena, GThakur. 2022. Artificial intelligence and machine learning applications in biopharmaceutical manufacturing. Trends in Biotechnology