Achieving favorable product quality attributes begins with optimizing cell line development, including the early identification and proper selection of a clone. Biomanufacturers are working toward higher yields and improved cell quality by using high-throughput screening methods and advanced gene editing methods. This featured report focuses on different factors of cell line development quality and how they affect the quality of a final drug product.
by Maribel Rios
Cell engineering is used to enhance biomanufacturing and improve titer and product quality. This introduction includes highlights from the cell line development track at the July 2020 BioProcess International Europe conference. Presenters focused on current cell line development trends such as the implementation of automated and digital systems, synthetic biology, and machine learning for single-cell imaging. Other presentations highlighted the optimization of cell lines, bispecific antibody cell lines, and high-throughput screening.
Applications of CRISPR and Other Gene Editing Tools in Cell Line Development and Engineering
by Dan Piestun
Researchers continue to demonstrate how clustered, regularly interspersed palindromic repeats (CRISPR) techniques can improve the engineering of chimeric antigen receptor (CAR) T cells and delivery of CARs to specific sites within T cells. The ability to edit genetic material relatively inexpensively, effectively, and quickly is useful in the treatment of genetic diseases, particularly those in which point mutations in genes are wholly responsible for a disease phenotype. This article explores the use of CRISPR and similar gene editing methods in cell line development, including improving glycosylation profiles and engineering posttranslational modifications in different cell culture systems.
Cell-Line Quality: Direct Analysis of Bioreactor Harvest for Clone Selection and Process Optimization
by Guanglou Cheng, Abhijit Shirke, Linas Antoniukas, Dharmesh Kanani, John Kim, and Bing Hu
Several factors can influence product quality. The authors analyze bioreactor harvests of mammalian cell cultures to provide a useful guide in clone selection and to optimize bioprocesses. Such analyses facilitate characterization and monitoring to improve drug substance purity and safety. The authors also address the advantages of analyzing bioreactor harvest directly using routine or modified separation methods without the need for product purification, thereby saving manufacturers time and resources.
Plant-Cell Expression and Cell Line Development
by Brian Gazaille and Maribel Rios, with Einat Brill Almon and Eyal Rubin
Plant-cell expression systems have several advantages over other cell cultures. Plant cells can produce complex proteins with posttranslational modifications, and plant-cell culture is easier and more cost effective than mammalian- and bacterial-based systems. Protalix Biotherapeutics is developing recombinant therapeutic proteins by developing plant-based cell banks for culture amplification and production.