title: Proposal for a new protein therapeutic immunogenicity titer assay cutpoint.
abstract: BACKGROUND
  Generally, immunogenicity assessment strategies follow this assay triage schema: screen→confirm→titer. Each requires the determination of a threshold value (cutpoint) for decision making. No guidance documents exist for the determination of a specific titration assay cutpoint. The default practice is to use the screening assay cutpoint, frequently leading to controls or samples not reaching this cutpoint. We propose a method for determination of a titration cutpoint based upon the variance of the negative-control sample.
  
  
  RESULTS
  Positive-control samples that did not cross a screening cutpoint did cross the titer cutpoint, albeit generating slightly lower titer values.
  
  
  CONCLUSIONS
  Our approach is consistent with the statistical methods currently recommended for the screening and confirmatory assay cutpoints and is operationally simple and efficient.
authors.affiliation: Department of Bioanalytical Sciences, Genentech, South San Francisco, CA 94080, USA. wakshull.eric@gene.com
authors.forename: Eric
authors.initials: E
authors.lastname: Wakshull
authors.forename: Robert
authors.initials: R
authors.lastname: Hendricks
authors.forename: Caroline
authors.initials: C
authors.lastname: Amaya
authors.forename: Daniel
authors.initials: D
authors.lastname: Coleman
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000032:analysis* / Q000276:immunology; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D006801:Humans; D055261:Immunogenetic Phenomena; D007158:Immunologic Techniques / Q000379:methods*; D007159:Immunologic Tests; D018448:Models, Immunological; D011506:Proteins / Q000276:immunology*; D015203:Reproducibility of Results
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D011506:Proteins; C533411:ocrelizumab