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 Kyle Zingaro
A1 David Shaw
A1 Jerry Carson
A1 Anke Mayer-Bartschmid
A1 Christian Bender
A1 Christina Alves
A1 Duncan Mcvey
A1 Nan-Xin Qian
A1 Qingxiang Wei
A1 Michael W. Laird
A1 Yuan Zhu
A1 Robyn Emmins
A1 John A. Follit
A1 Alison Porter
A1 Andrew J. Racher
A1 Sarah Milne
A1 Ivan Carubelli
A1 Zhimei Du
A1 Ankita Khatri
A1 Marilyne Failly
A1 Hervé Broly
A1 Frank Lee
A1 Matthew Reeser
A1 Jared Spidel
A1 Karin Anderson
A1 Christine Demaria
A1 Jennifer Di-Carlo
A1 John Gill
A1 Amie Lundquist
A1 Sampath R. Kumar
A1 Tony Gill
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.