title: Implementation of a universal analytical method in early-stage development of human antibody therapeutics: application to pharmacokinetic assessment for candidate selection.
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.
  
  
  CONCLUSIONS
  This assay has wide applicability as a default bioanalytical approach in therapeutic candidate selection and preliminary pharmacokinetics evaluation during early-stage therapeutic development.
authors.affiliation: Department of Pharmacokinetic & Drug Metabolism, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA 91320, USA. shihj@amgen.com
authors.forename: Judy Y
authors.initials: JY
authors.lastname: Shih
authors.forename: Vimal
authors.initials: V
authors.lastname: Patel
authors.forename: Andrew
authors.initials: A
authors.lastname: Watson
authors.forename: Todd
authors.initials: T
authors.lastname: Hager
authors.forename: Peng
authors.initials: P
authors.lastname: Luan
authors.forename: Hossein
authors.initials: H
authors.lastname: Salimi-Moosavi
authors.forename: Mark
authors.initials: M
authors.lastname: Ma
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000276:immunology / Q000493:pharmacokinetics; D004797:Enzyme-Linked Immunosorbent Assay; D006207:Half-Life; D006736:Horses; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000032:analysis / Q000276:immunology; D051379:Mice; D044085:Microfluidics / Q000592:standards; D011323:Primates; D011786:Quality Control; D051381:Rats; D013552:Swine
chemical_list: D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments