Implementation of a universal analytical method in early-stage development of human antibody therapeutics: application to pharmacokinetic assessment for candidate selection

Bioanalysis. 2012 Oct;4(19):2357-65. doi: 10.4155/bio.12.201.

Abstract

Background: Effective bioanalytical support for pharmacokinetic assessment of therapeutics in early development remains challenging. Concurrent evaluation of multiple candidates per program is typical, requiring efficient characterization in various preclinical species; an ambitious effort often complicated by assay reagent unavailability and limited sample volume. Accordingly, a universal anti-human Fc assay for human monoclonal antibody and derived therapeutics was developed using a microfluidics platform to address these bioanalytical challenges.

Results: The universal assay with standardized format was qualified for quantitation of human IgG Fc-containing biotherapeutics in matrices from commonly used preclinical species. Results from this assay compared well with those from traditional colorimetric immunoassays. Furthermore, result comparison between the universal and target-specific assays provided additional information on the effect of antidrug antibodies and in vivo drug catabolism.

Conclusion: This assay has wide applicability as a default bioanalytical approach in therapeutic candidate selection and preliminary pharmacokinetics evaluation during early-stage therapeutic development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / analysis*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics
  • Enzyme-Linked Immunosorbent Assay
  • Half-Life
  • Horses
  • Humans
  • Immunoglobulin Fc Fragments / analysis
  • Immunoglobulin Fc Fragments / immunology
  • Mice
  • Microfluidics* / standards
  • Primates
  • Quality Control
  • Rats
  • Swine

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin Fc Fragments