title: Industry view on the relative importance of "clonality" of biopharmaceutical-producing cell lines.
abstract: Recently, several health authorities have requested substantial detail from sponsor firms regarding the practices employed to generate the production cell line for recombinant DNA-(rDNA) derived biopharmaceuticals. Two possible inferences from these regulatory agency questions are that (1) assurance of "clonality" of the production cell line is of major importance to assessing the safety and efficacy of the product and (2), without adequate proof of "clonality", additional studies of the cell line and product are often required to further ensure the product's purity and homogeneity. Here we address the topic of "clonality" in the broader context of product quality assurance by current technologies and practices, as well as discuss some of the relevant science and historical perspective. We agree that the clonal derivation of a production cell line is one factor with potential impact, but it is only one of many factors. Further, we believe that regulatory emphasis should be primarily placed on ensuring product quality of the material actually administered to patients, and on ensuring process consistency and implementing appropriate control strategies through the life cycle of the products.
authors: Eli Lilly & Company, Indianapolis, IN 46285, United States. Electronic address: ccfrye@lilly.com.
authors: Christopher
authors: C
authors: Frye
authors: Amgen Inc, Thousand Oaks, CA, United States.
authors: Rohini
authors: R
authors: Deshpande
authors: Biogen Inc, Cambridge, MA, United States.
authors: Scott
authors: S
authors: Estes
authors: Genentech Inc, South San Francisco, CA, United States.
authors: Kathy
authors: K
authors: Francissen
authors: Genentech Inc, South San Francisco, CA, United States.
authors: John
authors: J
authors: Joly
authors: Janssen R&D LLC, Malvern, PA, United States.
authors: Anthony
authors: A
authors: Lubiniecki
authors: Amgen Inc, Thousand Oaks, CA, United States.
authors: Trent
authors: T
authors: Munro
authors: Bristol Myers Squibb, Pennington, NJ, United States.
authors: Reb
authors: R
authors: Russell
authors: Eli Lilly & Company, Indianapolis, IN 46285, United States.
authors: Tongtong
authors: T
authors: Wang
authors: Pfizer Inc, Andover, MA, United States.
authors: Karin
authors: K
authors: Anderson
mesh_terms: D000818:Animals; D001702:Biopharmaceutics / Q000592:standards*; D018929:Cell Culture Techniques / Q000592:standards*; D002460:Cell Line; D006801:Humans; D013678:Technology, Pharmaceutical / Q000592:standards*
keywords: Biopharmaceuticals; Chinese hamster ovary cells; Clonality; ICH guidelines; Product control strategy; Production cell line