A Novel Approach to Evaluate the Pharmacokinetic Biocomparability of a Monoclonal Antibody Derived from Two Different Cell Lines Using Simultaneous Crossover Design

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• 作者：Chao Han (1)
  Thomas S. McIntosh (1)
  Brian J. Geist (1)
  Trina Jiao (1)
  Thomas A. Puchalski (1)
  Kenneth M. Goldberg (2)
  Tong-Yuan Yang (1)
  Charles E. Pendley (1)
  Honghui Zhou (1)
  Hugh M. Davis (1)
  
• 关键词：liquid chromatography ; mass spectrometry (LC/MS) ; monoclonal antibody ; pharmacokinetic biocomparability ; siltuximab ; simultaneous crossover
• 刊名：The AAPS Journal
• 出版年：2014
• 出版时间：January 2014
• 年：2014
• 卷：16
• 期：1
• 页码：125-128
• 全文大小：264 KB
• 作者单位：Chao Han (1)
  Thomas S. McIntosh (1)
  Brian J. Geist (1)
  Trina Jiao (1)
  Thomas A. Puchalski (1)
  Kenneth M. Goldberg (2)
  Tong-Yuan Yang (1)
  Charles E. Pendley (1)
  Honghui Zhou (1)
  Hugh M. Davis (1)
  
  1. Biologics Clinical Pharmacology, Janssen Research & Development, LLC, Spring House, Pennsylvania, 19477, USA
  2. Nonclinical Statistics & Computing, Janssen Research & Development, LLC, Spring House, Pennsylvania, 19477, USA
  
• ISSN：1550-7416

文摘

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.