title: Validation of an integrated series of ligand-binding assays for the quantitative determination of antibody-drug conjugates in biological matrices.
abstract: BACKGROUND
  The bioanalytical strategy for antibody-drug conjugates (ADC) includes multiple integrated measurements of pharmacologically relevant ADC.
  
  
  RESULTS
  Three ligand-binding assays were validated for the measurement of total antibody, active ADC and total ADC. Accuracy and precision demonstrate %bias from -8 to 14%, %CV from 3 to 11% and total error from 3 to 21%, with >98% samples meeting incurred sample reanalysis criteria. Each assay met stability, selectivity, dilutional integrity, carry over and specificity criteria with no interference from associated metabolite/impurity. Given the active ADC assay sensitivity to payload, active ADC was used to assess drug to antibody ratio.
  
  
  CONCLUSIONS
  Implementation of a microfluidic automated platform enabled high throughput sample analysis of multiple analytes with minimal sample processing.
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Myler
authors.affiliation: Biologics Discovery California, Bristol-Myers Squibb, Redwood City, CA, USA.
authors.forename: Vangipuram S
authors.initials: VS
authors.lastname: Rangan
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Kozhich
authors.affiliation: Immunochemistry, PPD Laboratories®, Richmond, VA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Hoffpauir
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Dail
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cummings
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Saewert
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Manney
authors.affiliation: Bioanalytical Sciences-LCMS, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Ang
authors.initials: A
authors.lastname: Liu
authors.affiliation: Biologics Discovery California, Bristol-Myers Squibb, Redwood City, CA, USA.
authors.forename: Chetana
authors.initials: C
authors.lastname: Rao
authors.affiliation: Bioanalytical Sciences-LCMS, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
authors.forename: Renuka
authors.initials: R
authors.lastname: Pillutla
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
authors.forename: Binodh
authors.initials: B
authors.lastname: DeSilva
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry; D006207:Half-Life; D007118:Immunoassay / Q000592:standards; D018796:Immunoconjugates / Q000032:analysis* / Q000493:pharmacokinetics; D017705:Lignans; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011786:Quality Control
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D017705:Lignans; D004364:Pharmaceutical Preparations
keywords: antibody–drug conjugate; drug antibody ratio; ligand-binding assays; payload; selectivity; specificity; total antibody