(186d) Implementation of Molecular Biology and Cell Line Development Courses for Future Engineers in Biopharmaceutical Industry.

The success of the biotechnology industry relies largely on a highly educated and skilled workforce. Chemical engineers in careers related to the manufacturing of biopharmaceuticals engage with critical aspects in diverse upstream and/ or downstream processes such as the design and development of protein expression systems, or the production, purification and formulation of a therapeutic protein of interest. In order to empower graduate and undergraduate students with a strong understanding of the biomanufacturing workflow, we have designed two closely linked hands-on courses at North Carolina State University’s Biomanufacturing Training and Education Center (BTEC) that emphasize the fundamentals of molecular biology and cell line development. The first course entitled “Molecular biology for biomanufacturing” exposes students to detailed principals and techniques allowing the comprehension of key steps in the establishment of a prokaryotic expression system. The lecture component covers fundamentals of genetics and physiology of prokaryotes, while the laboratory section of the course provides the students with a valuable opportunity to genetically engineer a bacterium for the production of a protein of interest. Experimental tasks include the cloning of the gene of interest on a specific expression vector, selection and screening of bacterium with the recombinant vector, small scale fermentation and production, followed by identification, quantification and testing the activity of the produced protein using specific analytical methods. The second course “Cell line development for biomanufacturing” highlights key aspects in the generation of mammalian and yeast expression systems using two cell types that are widely used in the biopharmaceutical industry. We underline specific cloning and expression considerations that are pertinent to eukaryotic systems with special emphasis on cell culture techniques, metabolic engineering using CRISPR technology, cell banking and good manufacturing practices. After producing the same protein in all three expression systems, students appreciate the advantages and disadvantages of each cell type at different levels including the process time, productivity, cost and activity. Keeping in mind the applicability of the courses learning objectives to biomanufacturing, the lectures and laboratory material have been developed to nurture the concept of maximum productivity of a protein with the desired quality attributes, facilitating the downstream processing, and how to troubleshoot possible bottlenecks. In addition to students in chemical engineering these two courses serve a number of other graduate and undergraduate programs at NC state university, including those majoring in biomedical engineering, chemistry, and biochemistry. Further, we have established an intensive short version of the two courses, conducted over three days, to train scientists from biopharmaceutical industry. Details of the courses and their impact on the biomanufacturing industry will be discussed.