The Relevance of Immunogenicity in Preclinical Development

Ciriaco Maraschiello

Abstract

This communication discusses the relevance of immunogenicity in preclinical trials and its importance in the development of biopharmaceuticals. The preclinical and non clinical development of Biopharmaceuticals is reviewed and discussed, with a focus on the specific regulatory requirements for the preclinical and clinical safety assessment of large molecules. Immunogenicity data obtained for Interferon and Rituximab during preclinical safety assessment studies are presented in this communication. Interferon and Rituximab are biopharmaceuticals that have been demonstrated to elicit immunogenic reactions in both preclinical animal models and clinical trials. The production of Anti-Drug Antibodies (ADAs) has several consequences on the systemic exposure and on the toxicity/ pharmacodynamic profile of a biopharmaceutical assessed in the preclinical stage. The impact must be carefully assessed especially when using the preclinical data to establish the Maximum Recommended Safe Starting Dose (MRSD) of the first clinical trials.