Mechanisms Underlying the Immunogenicity of Therapeutic Proteins: Risk Assessment and Management Strategies.

Antibodies to therapeutic proteins have caused serious adverse events and loss of efficacy in patients. Therefore, it is critical to manage the risk of antitherapeutic antibodies (ATA) during drug development and in the postmarketing environment. Risk assessments are an important tool for managing immunogenicity risk because they provide a format for considering the consequences and likelihood of ATA development. Because many factors influence both the severity of the consequences and likelihood of ATA development, successful risk assessments require input from all relevant disciplines, including product quality, manufacturing, nonclinical, pharmacology, and clinical. The results of risk assessments are used to develop appropriate risk reduction strategies, which may include product quality and manufacturing controls and elements of clinical trial design. This article discusses considerations for immunogenicity risk assessments and management.