Scientific and regulatory considerations on the immunogenicity of biologics.

Immune responses against non-vaccine biologics can affect their efficacy and safety, resulting in adverse events that could include administration reactions, hypersensitivity, deficiency syndromes and lack of a clinical response in treated patients. With the relatively recent development of numerous biologics, immunogenicity testing has become a key component in the demonstration of clinical safety and efficacy; in fact, it is highly unlikely that regulatory approval would be granted for a biologic without an assessment of its immunogenicity. However, recommendations from regulatory agencies regarding the requirements for when and how to carry out immunogenicity testing are dispersed among numerous guidance documents. To enable the evaluation of the effects of immunogenicity on safety and efficacy, the authors have consolidated recommendations from the regulatory guidelines, and present current approaches and future directions for the assessment of immunogenicity.