Small Molecule Reactions
Over the last four years, a very productive collaborative research project with colleagues from Pfizer and Merck has enabled our novel DRSM methodology to model time-resolved concentration data from small-molecule reaction experiments. Very accurate models were obtained that describe the evolution of all measured concentrations in time and, simultaneously, for all values of the factors. These models modeled very effectively the time evolution of intermediate compounds and byproducts as well as the primary reactants and products. More about the DRSM models can be found here.
With the DRSM models of the measured species at hand, one can start investigating the stoichiometry of the possible reactions. More about this significant step in transforming data-driven models into knowledge-driven kinetic models can be found here.
Several publications detail the results of this productive collaboration:
- Dong, Y. C., C. Georgakis, J. Mustakis, J. M. Hawkins, L. Han, K. Wang, J. P. McMullen, S. T. Grosser, and K. Stone. 2019. ‘Constrained Version of the Dynamic Response Surface Methodology for Modeling Pharmaceutical Reactions’, Ind. & Eng. Chem. Res., 58, (30): 13611-21. DOI: http://doi.org/10.1021/acs.iecr.9b00731
- Dong, Y. C., C. Georgakis, J. Mustakis, J. M. Hawkins, L. Han, K. Wang, J. P. McMullen, S. T. Grosser, and K. Stone. 2019. ‘Stoichiometry identification of pharmaceutical reactions using the constrained dynamic response surface methodology’, AIChE J., 65 (11) DOI: http://doi.org/10.1002/aic.16726
- Santos-Marques, J., C. Georgakis, J. Mustakis, and J. M. Hawkins. 2019. “From dynamic response surface models to the identification of the reaction stoichiometry in a complex pharmaceutical case study”, AIChE J., 65 (4): 1173-85. DOI: http://doi.org/10.1002/aic.16515
- Dong, Y. C., C. Georgakis, J. Mustakis, L. Han, and J. P. McMullen. 2020. “Optimization of Pharmaceutical Reactions using the Dynamic Response Surface Methodology”, Comp. & Chem. Eng., 135: 106778. http://doi.org/10.1016/j.compchemeng.2020.106778
This project is entering a second phase in the fall of 2020 with one or, possibly, two additional companies sharing the funding and offering technical input.
Cell Culture Processes
Both the DoDE and DRSM methodologies are perfectly suited for the modeling and optimization of cell culture processes. In an effort to demonstrate their power, we have entered into a collaborative effort with researchers in Biogen to benchmark the effectiveness of the methodology to a typical cell culture process.
- Dong, Y. C., C. Georgakis, J. Mustakis, J. M. Hawkins, L. Han, K. Wang, J. P. McMullen, S. T. Grosser, and K. Stone. 2019. ‘Constrained Version of the Dynamic Response Surface Methodology for Modeling Pharmaceutical Reactions’, Ind. & Eng. Chem. Res., 58, (30): 13611-21. DOI: http://doi.org/10.1021/acs.iecr.9b00731
- Dong, Y. C., C. Georgakis, J. Mustakis, J. M. Hawkins, L. Han, K. Wang, J. P. McMullen, S. T. Grosser, and K. Stone. 2019. ‘Stoichiometry identification of pharmaceutical reactions using the constrained dynamic response surface methodology’, AICHE J., 65 (11) DOI: http://doi.org/10.1002/aic.16726
- Santos-Marques, J., C. Georgakis, J. Mustakis, and J. M. Hawkins. 2019. “From dynamic response surface models to the identification of the reaction stoichiometry in a complex pharmaceutical case study”, AIChE J., 65 (4): 1173-85. DOI: http://doi.org/10.1002/aic.16515
- Dong, Y. C., C. Georgakis, J. Mustakis, L. Han, and J. P. McMullen. 2020. “Optimization of Pharmaceutical Reactions using the Dynamic Response Surface Methodology”, Comp. & Chem. Eng., 135: 106778. http://doi.org/10.1016/j.compchemeng.2020.106778