Strategy and validation of a nonclinical generic plug-and-play antidrug antibody method for human monoclonal antibody biotherapeutics.

The measurement of antidrug antibodies (ADA) in nonclinical studies provides limited value because the formation and incidence of nonclinical ADA does not translate to clinical experience. The formation and presence of ADA in nonclinical species can, however, correlate to reduced drug exposure and safety observations including vasculitis and immune complex disease. Generic ADA methods for humanized monoclonal antibody biotherapeutics mitigate the need to develop bespoke ADA methods during nonclinical drug development. A drug-tolerant, sensitive, generic ADA immunoassay has been developed and validated for measuring ADA in cynomolgus monkey serum samples, allowing for immediate qualification of future monoclonal antibody biotherapeutics. This approach allows us to differentiate complexed and free ADA in a rapidly deployable manner when needed. The testing of antidrug antibodies (ADA) in animal studies offers low value because the presence of animal ADA does not translate to human studies. However, the impact of ADA can be seen with reduced drug levels and/or safety findings in animal studies. Generic ADA methods offer a way to measure ADA leading to time and cost savings. This article details the testing of a generic plug-and-play method to measure ADA in monkey serum and how to qualify future drugs. To date, 16 drugs have been qualified using this method, which has also been applied to mouse, rat and rabbit serum.