title: Strategies to estimate and improve drug tolerance in anti-drug antibody assays.
abstract: BACKGROUND
  Drug tolerance of anti-drug antibody (ADA) assays is becoming increasingly important due to the high number of newly emerging long-acting drugs. Methods to estimate and improve drug tolerance in ADA assays are needed.
  
  
  RESULTS
  The relevance and precision of drug tolerance estimates in a bridging ELISA depended on characteristics and concentration of the surrogate control antibody together with assay cut point level. Stepwise and coincubation procedures were optimized for drug tolerance and sensitivity by adapting concentrations of reagents used for capture and detection of ADAs. In combination with acid treatment of samples, increase in drug tolerance of over 20-fold was achieved without losing sensitivity in two different assays. Acid treatment reduced drug interference observed in preclinical samples and prevented underestimation of ADA response.
  
  
  CONCLUSIONS
  In a risk-based approach it may be possible to reliably predict in vivo drug tolerance using carefully chosen surrogate controls. General guidelines for development of drug-tolerant bridging ELISAs are presented.
authors.affiliation: Celerion Switzerland AG, Allmendstrasse 32, 8320 Fehraltorf, ZH, Switzerland. lukas.butikofer@celerion.com
authors.forename: Lukas
authors.initials: L
authors.lastname: Bütikofer
authors.forename: Guy
authors.initials: G
authors.lastname: Lemaillet
authors.forename: Heinrich
authors.initials: H
authors.lastname: Faust
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology; D001710:Biotin; D004361:Drug Tolerance; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D056724:Immunity, Humoral; D011994:Recombinant Proteins / Q000276:immunology; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D057057:Serine Proteases / Q000276:immunology; D019809:Streptavidin
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D011994:Recombinant Proteins; D001710:Biotin; D019809:Streptavidin; D057057:Serine Proteases