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The AAPS Journal

, Volume 16, Issue 1, pp 125–128 | Cite as

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

  • Chao Han
  • Thomas S. McIntosh
  • Brian J. Geist
  • Trina Jiao
  • Thomas A. Puchalski
  • Kenneth M. Goldberg
  • Tong-Yuan Yang
  • Charles E. Pendley
  • Honghui Zhou
  • Hugh M. Davis
Brief/Technical Note

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.

KEY WORDS

liquid chromatography-mass spectrometry (LC/MS) monoclonal antibody pharmacokinetic biocomparability siltuximab simultaneous crossover 

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Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • 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. 1.Biologics Clinical PharmacologyJanssen Research & Development, LLCSpring HouseUSA
  2. 2.Nonclinical Statistics & ComputingJanssen Research & Development, LLCSpring HouseUSA

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