title: A novel approach to evaluate the pharmacokinetic biocomparability of a monoclonal antibody derived from two different cell lines using simultaneous crossover design.
abstract: A parallel study design with a large number of subjects has been a typical path for pharmacokinetic (PK) biocomparability assessment of biotherapeutics with long half-lives and immunogenic propensity, for example, monoclonal antibodies (mAb). A recently published innovative bioanalytical method that can quantify mAb produced from two different cell lines in the same sample opened an avenue to exploring a simultaneous crossover study design for PK biocomparability assessment of biotherapeutics. Siltuximab, a chimeric IgG1 mAb-targeting interleukin-6, was studied as an example. The pharmacokinetic biocomparability of siltuximab derived from mouse myeloma (Sp2/0) cells and Chinese hamster ovary cells was previously assessed and demonstrated in a clinical PK biocomparability study that enrolled more than 140 healthy subjects using a parallel trial design. The biocomparability was successfully shown in six cynomolgus monkeys in a preclinical proof-of-concept study using the new crossover study design supported by the analytical method. The impact of antidrug antibodies on the assessment of biocomparability was minimal. This novel approach opened up a new arena for the evaluation of PK biocomparability of biotherapeutics with unique molecular signatures such as a mAb derived from different cell lines.
authors.affiliation: Biologics Clinical Pharmacology, Janssen Research & Development, LLC, Spring House, Pennsylvania, 19477, USA, chan@its.jnj.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Han
authors.forename: Thomas S
authors.initials: TS
authors.lastname: McIntosh
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Geist
authors.forename: Trina
authors.initials: T
authors.lastname: Jiao
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Puchalski
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Goldberg
authors.forename: Tong-Yuan
authors.initials: TY
authors.lastname: Yang
authors.forename: Charles E
authors.initials: CE
authors.lastname: Pendley
authors.forename: Honghui
authors.initials: H
authors.lastname: Zhou
authors.forename: Hugh M
authors.initials: HM
authors.lastname: Davis
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018592:Cross-Over Studies; D004353:Drug Evaluation, Preclinical; D005069:Evaluation Studies as Topic; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D013810:Therapeutic Equivalency
chemical_list: D000911:Antibodies, Monoclonal; C504234:siltuximab