Immunogenicity Risks for Naturally Derived Complex Drugs

Naturally derived complex drugs (NDCD) can elicit undesired immune responses that impact on the safety and efficacy of therapeutic products. In recent years, our understanding of the product- and patient-related factors that impact on the immunogenicity of therapeutics has grown considerably. Despite this and the continuous improvement of bioanalytical and immunological methods, it is not yet possible to predict with certainty whether a product will be immunogenic, identify the subset of patients at risk, and foresee how the immune response will impact the clinical outcome. The question of immunogenicity risk is particularly complex for the development and regulation of NDCD where the identity and contribution of individual product components to the product immunogenicity is largely unknown. This chapter describes the clinical considerations of product immunogenicity and provides an overview of known patient- and product-related risk factors emphasizing the unique complexities of NDCD.