TY - JOUR T1 - Implementation of Plate Imaging for Demonstration of Monoclonality in Biologics Manufacturing Development JF - PDA Journal of Pharmaceutical Science and Technology JO - PDA J Pharm Sci Technol SP - 438 LP - 450 DO - 10.5731/pdajpst.2018.008789 VL - 72 IS - 4 AU - Kyle Zingaro AU - David Shaw AU - Jerry Carson AU - Anke Mayer-Bartschmid AU - Christian Bender AU - Christina Alves AU - Duncan Mcvey AU - Nan-Xin Qian AU - Qingxiang Wei AU - Michael W. Laird AU - Yuan Zhu AU - Robyn Emmins AU - John A. Follit AU - Alison Porter AU - Andrew J. Racher AU - Sarah Milne AU - Ivan Carubelli AU - Zhimei Du AU - Ankita Khatri AU - Marilyne Failly AU - Hervé Broly AU - Frank Lee AU - Matthew Reeser AU - Jared Spidel AU - Karin Anderson AU - Christine Demaria AU - Jennifer Di-Carlo AU - John Gill AU - Amie Lundquist AU - Sampath R. Kumar AU - Tony Gill Y1 - 2018/07/01 UR - http://journal.pda.org/content/72/4/438.abstract N2 - Monoclonality of mammalian cell lines used for production of biologics is a regulatory expectation and one of the attributes assessed as part of a larger process to ensure consistent quality of the biologic. Historically, monoclonality has been demonstrated through statistics generated from limiting dilution cloning or through verified flow cytometry methods. A variety of new technologies are now on the market with the potential to offer more efficient and robust approaches to generating and documenting a clonal cell line.Here we present an industry perspective on approaches for the application of imaging and integration of that information into a regulatory submission to support a monoclonality claim. These approaches represent the views of a consortium of companies within the BioPhorum Development Group and include case studies utilising imaging technology that apply scientifically sound approaches and efforts in demonstrating monoclonality. By highlighting both the utility of these alternative approaches and the advantages they bring over the traditional methods, as well as their adoption by industry leaders, we hope to encourage acceptance of their use within the biologics cell line development space and provide guidance for regulatory submission using these alternative approaches.LAY ABSTRACT: In the manufacture of biologics produced in mammalian cells, one recommendation by regulatory agencies to help ensure product consistency, safety, and efficacy is to produce the material from a monoclonal cell line derived from a single, progenitor cell. The process by which monoclonality is assured can be supplemented with single-well plate images of the progenitor cell. Here we highlight the utility of that imaging technology, describe approaches to verify the validity of those images, and discuss how to analyze that information to support a biologic filing application. This approach serves as an industry perspective to increased regulatory interest within the scope of monoclonality for mammalian cell culture–derived biologics. ER -