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 Paul Wu
A1 Taymar Hartman
A1 Louise Almond
A1 Jennitte Stevens
A1 John Thrift
A1 Juhi Ojha
A1 Christina Alves
A1 David Shaw
A1 Michael W. Laird
A1 Robyn Emmins
A1 Yuan Zhu
A1 Ren Liu
A1 Zhimei Du
A1 Rolf Koehler
A1 Thomas Jostock
A1 Karin Anderson
A1 Chris Campbell
A1 Howard Clarke
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.