title: Recommendations for the design, optimization, and qualification of cell-based assays used for the detection of neutralizing antibody responses elicited to biological therapeutics.
abstract: The administration of biological therapeutics can evoke some level of immune response to the drug product in the receiving subjects. An immune response comprised of neutralizing antibodies can lead to loss of efficacy or potentially more serious clinical sequelae. Therefore, it is important to monitor the immunogenicity of biological therapeutics throughout the drug product development cycle. Immunoassays are typically used to screen for the presence and development of anti-drug product antibodies. However, in-vitro cell-based assays prove extremely useful for the characterization of immunoassay-positive samples to determine if the detected antibodies have neutralizing properties. This document provides scientific recommendations based on the experience of the authors for the development of cell-based assays for the detection of neutralizing antibodies in non-clinical and clinical studies.
authors.affiliation: Clinical Immunology, Amgen Inc., Thousand Oaks, CA 91320, USA. shalinig@amgen.com
authors.forename: Shalini
authors.initials: S
authors.lastname: Gupta
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Indelicato
authors.forename: Vijay
authors.initials: V
authors.lastname: Jethwa
authors.forename: Thomas
authors.initials: T
authors.lastname: Kawabata
authors.forename: Marian
authors.initials: M
authors.lastname: Kelley
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Mire-Sluis
authors.forename: Susan M
authors.initials: SM
authors.lastname: Richards
authors.forename: Bonita
authors.initials: B
authors.lastname: Rup
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shores
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Swanson
authors.forename: Eric
authors.initials: E
authors.lastname: Wakshull
mesh_terms: D000818:Animals; D000906:Antibodies / Q000032:analysis* / Q000276:immunology; D001681:Biological Assay / Q000379:methods* / Q000592:standards; D001688:Biological Products / Q000276:immunology* / Q000627:therapeutic use; D002138:Calibration; D002460:Cell Line; D017408:Guidelines as Topic; D006801:Humans; D007118:Immunoassay / Q000379:methods* / Q000592:standards; D009500:Neutralization Tests / Q000379:methods; D012015:Reference Standards; D015203:Reproducibility of Results; D012107:Research Design; D012680:Sensitivity and Specificity
chemical_list: D000906:Antibodies; D001688:Biological Products