Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology products

J Immunol Methods. 2004 Jun;289(1-2):1-16. doi: 10.1016/j.jim.2004.06.002.

Abstract

Most biopharmaceutical therapeutics elicit some level of antibody response against the product. This antibody response can, in some cases, lead to potentially serious side effects and/or loss of efficacy. Therefore, the immunogenicity of therapeutic proteins is a concern for clinicians, manufacturers and regulatory agencies. In order to assess immunogenicity of these molecules, appropriate detection, quantitation and characterization of antibody responses are necessary. Inadequately designed antibody assays have led to the hampering of product development or, during licensure, post-marketing commitments. This document provides scientific recommendations based on the experience of the authors for the development of anti-product antibody immunoassays intended for preclinical or clinical studies. While the main focus of this document is assay design considerations, we provide scientific focus and background to the various assay performance parameters necessary for developing a valid assay. Sections on assay performance parameters, including those that appear in regulatory guidances, are contained in this manuscript.

Publication types

  • Guideline
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / analysis*
  • Antibodies / blood
  • Biological Products / immunology*
  • Biotechnology*
  • Drug-Related Side Effects and Adverse Reactions
  • Humans
  • Immunoassay / standards*

Substances

  • Antibodies
  • Biological Products