Early development of therapeutic biologics--pharmacokinetics.

Modern biologics are biotechnology-derived pharmaceuticals. They are mostly used for diagnosis, prevention and treatment of serious and chronic diseases. Today, therapeutic biologics range from traditional biologics like blood and blood components, fractionated blood products, and antitoxins to modern biologics such as monoclonal antibodies, cytokines (e.g. interferon, interleukine), tissue growth factors, vaccines directed against non-infectious disease targets, and gene transfer products. Chemical as well as pre-clinical development are major challenges for biologics due to their different physicochemical properties (mostly protein structure) compared to small molecules. They demonstrate much more complex pharmacokinetic behaviour, which strongly influences their pre-clinical testing strategy. Biologics are often highly species-specific in action and immunogenic in test animal species and humans. Immunogenicity of therapeutic biologics may influence their pharmacokinetic behaviour as well as pharmacodynamics and toxicity. Biologics are frequently regulated by different procedures compared to small molecules. New guidances are evolving which reflect the rapid development of new technologies in this field. Bioanalytical method development and validation is a prerequisite not exclusively for pharmacokinetic studies but for the whole pre-clinical and clinical development. Due to their unique properties, different kinds of bioanalytical assays (mass assays, activity assays, immunogenicity assays) are necessary in early development of biologics.