PT  - JOURNAL ARTICLE
AU  - Paul Wu
AU  - Taymar Hartman
AU  - Louise Almond
AU  - Jennitte Stevens
AU  - John Thrift
AU  - Juhi Ojha
AU  - Christina Alves
AU  - David Shaw
AU  - Michael W. Laird
AU  - Robyn Emmins
AU  - Yuan Zhu
AU  - Ren Liu
AU  - Zhimei Du
AU  - Rolf Koehler
AU  - Thomas Jostock
AU  - Karin Anderson
AU  - Chris Campbell
AU  - Howard Clarke
TI  - 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
AID  - 10.5731/pdajpst.2018.009316
DP  - 2020 Mar 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 264--274
VI  - 74
IP  - 2
4099  - http://journal.pda.org/content/74/2/264.short
4100  - http://journal.pda.org/content/74/2/264.full
SO  - PDA J Pharm Sci Technol2020 Mar 01; 74
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.