Bioanalytics – Biomolecular
2019 PharmSci 360
Immunogenicity of biotherapeutics is a major challenge for the development of new therapeutic proteins and of great importance to the pharmaceutical community. The generation of anti-drug antibodies (ADAs) against therapeutic proteins leads to formation of immune complexes (ICs) which can vastly influence drug activity and pharmacokinetics (PK). Furthermore, ICs can provoke adverse events, like hypersensitivity reactions. Detailed understanding of IC formation, structure and pharmacokinetics would significantly help in the interpretation of clinical data and improved drug development. However, due to lack of optimal bioanalytical methods, our knowledge in this field is very limited. In this session, the bioanalytical challenges will be discussed and the currently available methods will be critically reviewed. Then, a novel analytical approach will be proposed that combines various bioanalytical and biophysical methods which enabled the generation, characterization, and quantitative determination of defined ICs. Application of this methods allowed for the first time a size-specific IC pharmacokinetic analysis in in-vivo studies. The learnings of these studies help to expand our current understanding of how the formation of anti-drug antibodies alters the pharmacokinetic of a therapeutic protein. Detailed knowledge in this field is of increasing importance with the increasing complexity and the potential immunogenicity of modern therapeutic proteins. Last not least, drug-target IC analysis, also currently heavily discussed in industry, can profit from the described methods.