The development of biotherapeutics, particularly multi-domain biotherapeutics (MDBs) and antibody drug conjugates (ADCs), presents unique challenges due to their complexity and increased immunogenicity risks. Bioanalytical approaches play a pivotal role in addressing these challenges. Robust bioanalytical methods are essential for effectively assessing the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenic responses of novel biologics. Advanced techniques, such as multiplexed assays using ligand binding assays (LBAs) and Liquid Chromatography-Mass Spectrometry (LC-MS) methods, are employed to handle the complexity of MDBs and ADCs effectively. Additionally, high-resolution mass spectrometry can investigate the potential biotransformation of biologics directly in in vivo studies. Furthermore, the Context of Use (CoU) is critical for defining assay purposes across nonclinical and clinical settings, ensuring their relevance and efficiency. Regulatory compliance is paramount to ensure assays meet standards for drug approval. Practical considerations include assay sensitivity, specificity, and the method's ability to investigate the structural integrity of MDBs and ADCs in in vivo studies. This paper aims to review recent publications on the application of bioanalytical techniques, specifically LBA and LC-MS, in supporting the development of pioneering biotherapeutics. Additionally, it will discuss optimal strategies for bioanalytical methods and immunogenicity assessment.
Sirtori et al. (Tue,) studied this question.