PT  - JOURNAL ARTICLE
AU  - Zingaro, Kyle
AU  - Shaw, David
AU  - Carson, Jerry
AU  - Mayer-Bartschmid, Anke
AU  - Bender, Christian
AU  - Alves, Christina
AU  - Mcvey, Duncan
AU  - Qian, Nan-Xin
AU  - Wei, Qingxiang
AU  - Laird, Michael W.
AU  - Zhu, Yuan
AU  - Emmins, Robyn
AU  - Follit, John A.
AU  - Porter, Alison
AU  - Racher, Andrew J.
AU  - Milne, Sarah
AU  - Carubelli, Ivan
AU  - Du, Zhimei
AU  - Khatri, Ankita
AU  - Failly, Marilyne
AU  - Broly, Hervé
AU  - Lee, Frank
AU  - Reeser, Matthew
AU  - Spidel, Jared
AU  - Anderson, Karin
AU  - Demaria, Christine
AU  - Di-Carlo, Jennifer
AU  - Gill, John
AU  - Lundquist, Amie
AU  - Kumar, Sampath R.
AU  - Gill, Tony
TI  - Implementation of Plate Imaging for Demonstration of Monoclonality in Biologics Manufacturing Development
AID  - 10.5731/pdajpst.2018.008789
DP  - 2018 Jul 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 438--450
VI  - 72
IP  - 4
4099  - http://journal.pda.org/content/72/4/438.short
4100  - http://journal.pda.org/content/72/4/438.full
SO  - PDA J Pharm Sci Technol2018 Jul 01; 72
AB  - 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.