RT Journal Article
SR Electronic
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
FD Parenteral Drug Association (PDA)
SP 438
OP 450
DO 10.5731/pdajpst.2018.008789
VO 72
IS 4
A1 Zingaro, Kyle
A1 Shaw, David
A1 Carson, Jerry
A1 Mayer-Bartschmid, Anke
A1 Bender, Christian
A1 Alves, Christina
A1 Mcvey, Duncan
A1 Qian, Nan-Xin
A1 Wei, Qingxiang
A1 Laird, Michael W.
A1 Zhu, Yuan
A1 Emmins, Robyn
A1 Follit, John A.
A1 Porter, Alison
A1 Racher, Andrew J.
A1 Milne, Sarah
A1 Carubelli, Ivan
A1 Du, Zhimei
A1 Khatri, Ankita
A1 Failly, Marilyne
A1 Broly, Hervé
A1 Lee, Frank
A1 Reeser, Matthew
A1 Spidel, Jared
A1 Anderson, Karin
A1 Demaria, Christine
A1 Di-Carlo, Jennifer
A1 Gill, John
A1 Lundquist, Amie
A1 Kumar, Sampath R.
A1 Gill, Tony
YR 2018
UL http://journal.pda.org/content/72/4/438.abstract
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.