Immunogenicity Assay Development and Validation

Most approved biopharmaceuticals are immunogenic, resulting in varying incidence rates of antidrug antibodies that can cause clinical consequences ranging from benign to life threatening. For that reason, immunogenicity has become an important consideration in the development and approval of biopharmaceuticals. To assess the incidence and characteristics of antidrug antibodies, and to enable clinical correlations of laboratory results with clinical events, it is important to develop sensitive and reliable assays that provide valid assessments of antibody responses. Method validation is, therefore, a necessary bioanalytical component of biological drug marketing authorization applications. In this article, an overview is provided for assay development and validation for the assessment of binding antibodies as well as neutralizing antibodies. In addition, perspectives on efficiency and logistical considerations are provided for the immunogenicity bioanalytical laboratory.