title: Recommendations for the development and validation of confirmatory anti-drug antibody assays.
abstract: Identification and characterization of anti-drug antibodies is a critical component of biopharmaceutical drug development. The tiered approach for immunogenicity testing consists of screening, confirmatory, and characterization assays. Herein, we provide recommendations for confirmatory assays by expanding upon published guidance and present common practices across the industry. The authors recommend scientific approaches for development and validation of confirmatory assays using competition methods in ligand-binding assays, along with statistical formulae for routine use and validation. The paper will assist in understanding the confirmatory assay, and carefully implementing validation criteria a priori, as well as during sample analysis. These approaches represent the authors' current knowledge and practices, with the aim that more uniform practices will be applied across the industry.
authors.affiliation: Pfizer Inc., One Burtt Road, Andover, MA 01810, USA.
authors.forename: Darshana
authors.initials: D
authors.lastname: Jani
authors.affiliation: La Jolla Pharmaceutical Company, 10182 Telesis Court, 6th Floor, San Diego, CA 92121, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Marsden
authors.affiliation: Biogen Idec, Inc., 125 Broadway, Boston, MA 02142, USA.
authors.forename: Alvydas
authors.initials: A
authors.lastname: Mikulskis
authors.affiliation: Bristol-Myers Squibb, Route 206 & Province Line Road, Princeton, NJ 08540, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Gleason
authors.affiliation: Shire, 300 Shire Way, Lexington, MA 02421, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klem
authors.affiliation: Pfizer Inc., One Burtt Road, Andover, MA 01810, USA.
authors.forename: Corinna
authors.initials: C
authors.lastname: Krinos Fiorotti
authors.affiliation: Bristol-Myers Squibb, Route 206 & Province Line Road, Princeton, NJ 08540, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Myler
authors.affiliation: Covance, Inc., 3635 Concorde Parkway, Suite 100 Chantilly, VA 20151, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Covance, Inc., 3635 Concorde Parkway, Suite 100 Chantilly, VA 20151, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Fiscella
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000917:Antibody Formation; D001681:Biological Assay / Q000379:methods*; D015195:Drug Design; D006801:Humans
chemical_list: D000911:Antibodies, Monoclonal