title: Comparative study of therapeutic antibody candidates derived from mini-pool and clonal cell lines.
abstract: The long journey of developing a drug from initial discovery target identification to regulatory approval often leaves many patients with missed window of opportunities. Both regulatory agencies and biopharmaceutical industry continue to develop creative approaches to shorten the time of new drug development in order to deliver life-saving medicine to patients. Generally, drug substance materials to support the toxicology and early phase clinical study can only be manufactured after creating the final Master Cell Bank (MCB) of the clonally derived cell line, which normally takes 1-2 years. With recent advances in cell line development, cell culture process and analytical technologies, generating more homogeneous bulk/mini-pool population with higher productivity and acceptable quality attributes has become a norm, thereby making it possible to shorten the timeline to initiate First in Human (FIH) trial by using bulk/mini-pool generated materials to support toxicology and FIH studies. In this study, two monoclonal antibodies of different subclasses (IgG1 and IgG4) were expressed from the mini-pool cells as well as clonally derived cell lines generated from the same mini-pool. Cell growth, productivity, and product quality were compared between the materials generated from the mini-pool and clonally derived cell line. The results demonstrate the similarity of the antibody products generated from mini-pool cells and clonally derived cell lines from the same mini-pool, and strongly support the concept and feasibility of using antibody materials produced from mini-pool cultures for toxicology and FIH studies. The strategy to potentially shorten the FIH timeline is discussed. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1456-1462, 2017.
authors.affiliation: Cellular Molecular Biology, Bristol-Myers Squibb Company, Pennington, NJ, 08534.
authors.forename: Lianchun
authors.identifier: 0000-0002-6312-4823
authors.initials: L
authors.lastname: Fan
authors.affiliation: Cellular Molecular Biology, Bristol-Myers Squibb Company, Pennington, NJ, 08534.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rizzi
authors.affiliation: Cellular Molecular Biology, Bristol-Myers Squibb Company, Pennington, NJ, 08534.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Bierilo
authors.affiliation: Process Development, Bristol-Myers Squibb Company, Devens, MA, 01434.
authors.forename: Jun
authors.initials: J
authors.lastname: Tian
authors.affiliation: Process Development, Bristol-Myers Squibb Company, Devens, MA, 01434.
authors.forename: Joon Chong
authors.initials: JC
authors.lastname: Yee
authors.affiliation: Analytical and Process Development, Bristol-Myers Squibb Company, Pennington, NJ, 08534.
authors.forename: Reb
authors.initials: R
authors.lastname: Russell
authors.affiliation: Biologics Characterization & Analytical Development, Bristol-Myers Squibb Company, Pennington, NJ, 08534.
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Das
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061249:Batch Cell Culture Techniques / Q000639:trends; D019149:Bioreactors; D016466:CHO Cells / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D014116:Toxicology / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal
keywords: CHO cell; GS knockout; clonal-derived cell line; mini-pool; productivity; sequence variant; therapeutic monoclonal antibody