title: Recommendations for the validation of cell-based assays used for the detection of neutralizing antibody immune responses elicited against biological therapeutics.
abstract: The administration of biological therapeutics may result in the development of anti-drug antibodies (ADAs) in treated subjects. In some cases, ADA responses may result in the loss of therapeutic efficacy due to the formation of neutralizing ADAs (NAbs). An important characteristic of anti-drug NAbs is their direct inhibitory effect on the pharmacological activity of the therapeutic. Neutralizing antibody responses are of particular concern for biologic products with an endogenous homolog whose activity can be potentially dampened or completely inhibited by the NAbs leading to an autoimmune-type deficiency syndrome. Therefore, it is important that ADAs are detected and characterized appropriately using sensitive and reliable methods. The design, development and optimization of cell-based assays used for detection of NAbs have been published previously by Gupta et al. 2007 [1]. This paper provides recommendations on best practices for the validation of cell-based NAb assay and suggested validation parameters based on the experience of the authors.
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: Viswanath
authors.initials: V
authors.lastname: Devanarayan
authors.forename: Deborah
authors.initials: D
authors.lastname: Finco
authors.forename: George R
authors.initials: GR
authors.lastname: Gunn
authors.forename: Susan
authors.initials: S
authors.lastname: Kirshner
authors.forename: Susan
authors.initials: S
authors.lastname: Richards
authors.forename: Bonita
authors.initials: B
authors.lastname: Rup
authors.forename: An
authors.initials: A
authors.lastname: Song
authors.forename: Meena
authors.initials: M
authors.lastname: Subramanyam
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000917:Antibody Formation; D001681:Biological Assay / Q000379:methods; D001688:Biological Products / Q000276:immunology; D001798:Blood Proteins / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000592:standards; D006801:Humans; D007107:Immune System; D009500:Neutralization Tests; D004364:Pharmaceutical Preparations; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012984:Software
chemical_list: D057134:Antibodies, Neutralizing; D001688:Biological Products; D001798:Blood Proteins; D004364:Pharmaceutical Preparations