Cell-line development is more than just bioengineering. Every biomanufacturing process begins with transfection of recombinant genes into pools of cells — followed by a succession of screenings from which will emerge (ideally) a single progenitor cell of the new production cell line. But clonality is only part of the story. In this month’s featured report, we examine the latest advances in science and technology for transfecting, picking, screening, and adapting cell lines to the ideal conditions for producing therapeutic biomolecules as rapidly as possible. From new product modalities and biosimilars to continuous processing and serum-free media, the demands are high and the results can be rewarding.
Introduction: Reporting from the Frontiers of Cell Line Engineering
at BPI Europe and BPI West
Over the past several years, advancing technologies for genetic engineering, screening, clone selection, analysis, and data management have brought about a revolution in cell-line development. Audiences at the BioProcess International (BPI) conferences have watched this field evolve as presenters shared their insights and reported on their experiences. This year’s BPI Europe and BPI West events continued in that vein with presentations on technology platforms, clonality, cell-line (genetic) engineering, and development of biosimilars and other challenging product modalities. Here the senior technical editor reports on some of their discussions.
Creating New Cell Lines By Genome Editing for Novel Assays
and Easy Production of Biomolecules
by Masahito Yamagata, PhD (Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University)
Cultured cell lines are used by cell biologists, clinicians, tissue engineers, and biotechnologists. The most important uses are in cell-based assays and production of biologically active proteins. In recent years, genome editing has been used to study structure, function, and localization of endogenous proteins in cultured cells. Applied to cell lines, genome editing also could improve their efficiency and help devise novel assays to find new bioactive molecules. The author uses a cadherin adhesion molecule to explain how to use genome editing to generate new cell lines to meet those needs.
Streamlined Serum-Free Adaptation of CHO DG44 Cells
Using a Novel Chemically Defined Medium
by N. Moroni, A. Di Nunzio, A. Perli, R. Puca, K. Hammett, G. Piras, J. Brooks, and L. Sibilio (Menarini Biotech and BD Biosciences)
Upstream process development is strictly dependent on the availability of chemically defined media and feeds that are able to achieve high cell densities and MAb titers. This is particularly important for production of biosimilars, for which demand reduced cost of goods. Development of specific chemically defined media is a time and resources consuming activity and generally involves the use of statistic design. But use of media without components of animal origin is highly recommended by regulatory agencies. Biotech companies either use internally generated data from spent-media analysis and adjust their media formulations accordingly, or codevelop tailored media in collaboration with supplier companies. The choice depends on many factors, time and resources availability playing pivotal roles. Menarini Biotech developed a streamlined protocol to adapt a CHO DG44 cell line from adherent, serum supplemented culture to a fully chemically defined medium, suspension culture in only five weeks using a BD Biosciences protocol they found to be particularly suitable for biotech companies wishing to develop their own CHO DG 44 expression platforms.