RT Journal Article
SR Electronic
T1 Advancing Biologics Development Programs with Legacy Cell Lines: Advantages and Limitations of Genetic Testing for Addressing Clonality Concerns Prior to Availability of Late Stage Process and Product Consistency Data
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 264
OP 274
DO 10.5731/pdajpst.2018.009316
VO 74
IS 2
A1 Wu, Paul
A1 Hartman, Taymar
A1 Almond, Louise
A1 Stevens, Jennitte
A1 Thrift, John
A1 Ojha, Juhi
A1 Alves, Christina
A1 Shaw, David
A1 Laird, Michael W.
A1 Emmins, Robyn
A1 Zhu, Yuan
A1 Liu, Ren
A1 Du, Zhimei
A1 Koehler, Rolf
A1 Jostock, Thomas
A1 Anderson, Karin
A1 Campbell, Chris
A1 Clarke, Howard
YR 2020
UL http://journal.pda.org/content/74/2/264.abstract
AB The bioprocessing industry uses recombinant mammalian cell lines to generate therapeutic biologic drugs. To ensure consistent product quality of the therapeutic proteins, it is imperative to have a controlled production process. Regulatory agencies and the biotechnology industry consider cell line “clonal origin” an important aspect of maintaining process control. Demonstration of clonal origin of the cell substrate, or production cell line, has received considerable attention in the past few years, and the industry has improved methods and devised standards to increase the probability and/or assurance of clonal derivation. However, older production cell lines developed before the implementation of these methods, herein referred to as “legacy cell lines,” may not meet current regulatory expectations for demonstration of clonal derivation. In this article, the members of the IQ Consortium Working Group on Clonality present our position that the demonstration of process consistency and product comparability of critical quality attributes throughout the development life cycle should be sufficient to approve a license application without additional genetic analysis to support clonal origin, even for legacy cell lines that may not meet current day clonal derivation standards. With this commentary, we discuss advantages and limitations of genetic testing methods to support clonal derivation of legacy cell lines and wish to promote a mutual understanding with the regulatory authorities regarding their optional use during early drug development, subsequent to Investigational New Drug (IND) application and before demonstration of product and process consistency at Biologics License Applications (BLA) submission.