title: Strategies to Determine Assay Format for the Assessment of Neutralizing Antibody Responses to Biotherapeutics.
abstract: Most biotherapeutics can elicit immune responses in dosed recipients generating anti-drug antibodies (ADAs). Neutralizing antibodies (NAbs) are a subpopulation of ADAs that can potentially impact patient safety and directly mediate loss of drug efficacy by blocking the biological activity of a therapeutic product. Therefore, NAb detection is an important aspect of immunogenicity assessment, requiring sensitive and reliable methods reflective of the therapeutic mechanism of action (MoA). Both cell-based and non cell-based assays are viable options for NAb assessment. However, the scientific approach for the selection of a suitable assay format (cell-based or non cell-based) for NAb assessment is not currently well defined. In this manuscript, the authors summarize the design and utility of cell-based and non cell-based NAb assays and recommend a NAb assay format selection approach that relies on a combination of three factors. These include (i) the therapeutic MoA, (ii) the evidence of desirable assay performance characteristics, and (iii) risk of immunogenicity. The utility of correlating NAb response with pharmacodynamic data is also discussed. The aim of this paper is to provide a consistent strategy that will guide the selection of scientifically justified assay formats capable of detecting clinically relevant NAbs for biotherapeutics with varying MoAs and diverse complexity.
authors: Janssen Research & Development, LLC, Johnson & Johnson, 1400 McKean Road, P.O. Box 776, Spring House, Pennsylvania, 19477, USA. bwu23@its.jnj.com.
authors: Bonnie
authors: B
authors: Wu
authors: Genentech Inc., 1 DNA Way, South San Francisco, California, 94080, USA.
authors: Shan
authors: S
authors: Chung
authors: AstraZeneca, One MedImmune Way, Gaithersburg, Maryland, 20878, USA.
authors: Xu-Rong
authors: XR
authors: Jiang
authors: Pfizer, 1 Burtt Road, Andover, Massachusetts, 01810, USA.|EMD Serono, 45A Middlesex Turnpike, Billerica, Massachusetts, 01821, USA.
authors: Jim
authors: J
authors: McNally
authors: Center for Drug Evaluation and Research, Office of Biotechnology Products, Division of Biotech Review and Reseach III, Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA.
authors: Joao
authors: J
authors: Pedras-Vasconcelos
authors: Bristol-Myers Squibb, Route 206 & Provinceline Road, Princeton, New Jersey, 08543, USA.
authors: Renuka
authors: R
authors: Pillutla
authors: EMD Serono, 45A Middlesex Turnpike, Billerica, Massachusetts, 01821, USA.|Biogen, 250 Binney Street, Cambridge, Massachusetts, 02142, USA.
authors: Joleen T
authors: JT
authors: White
authors: Alnylam Pharmaceuticals, 300 Third Street, Cambridge, Massachusetts, 02142, USA.
authors: Yuanxin
authors: Y
authors: Xu
authors: Amgen, Inc., One Amgen Center Drive, Thousand Oaks, California, 91320, USA.
authors: Shalini
authors: S
authors: Gupta
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001688:Biological Products / Q000276:immunology*; D006801:Humans
chemical_list: D057134:Antibodies, Neutralizing; D001688:Biological Products
keywords: assay format; biotherapeutic; mechanism of action; neutralizing antibody