title: A statistical approach to determining criticality of residual host cell DNA.
abstract: We propose a method for determining the criticality of residual host cell DNA, which is characterized through two attributes, namely the size and amount of residual DNA in biopharmaceutical product. By applying a mechanistic modeling approach to the problem, we establish the linkage between residual DNA and product safety measured in terms of immunogenicity, oncogenicity, and infectivity. Such a link makes it possible to establish acceptable ranges of residual DNA size and amount. Application of the method is illustrated through two real-life examples related to a vaccine manufactured in Madin Darby Canine Kidney cell line and a monoclonal antibody using Chinese hamster ovary (CHO) cell line as host cells.
authors.affiliation: a MedImmune, LLC , Gaithersburg , Maryland , USA.
authors.forename: Harry
authors.initials: H
authors.lastname: Yang
authors.forename: Ziping
authors.initials: Z
authors.lastname: Wei
authors.forename: Mark
authors.initials: M
authors.lastname: Schenerman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000235:genetics; D001702:Biopharmaceutics / Q000592:standards / Q000706:statistics & numerical data*; D016466:CHO Cells; D002626:Chemistry, Pharmaceutical; D003257:Consumer Product Safety; D003412:Cricetulus; D004247:DNA / Q000032:analysis*; D003627:Data Interpretation, Statistical; D004285:Dogs; D004340:Drug Contamination / Q000706:statistics & numerical data*; D017408:Guidelines as Topic; D006801:Humans; D007252:Influenza Vaccines / Q000096:biosynthesis / Q000235:genetics / Q000592:standards; D061985:Madin Darby Canine Kidney Cells; D015233:Models, Statistical; D011786:Quality Control; D018570:Risk Assessment; D013678:Technology, Pharmaceutical / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data*
chemical_list: D000911:Antibodies, Monoclonal; D007252:Influenza Vaccines; D004247:DNA
keywords: Critical quality attribute; Infectivity; Oncogenicity; Quality by design; Residual host cell DNA; Risk assessment