Multi-Attribute Monitoring for QC Release Testing of a Therapeutic Nanobody was presented by Gwenael Nys from Sanofi in Geel, Belgium. Nys described Sanofi’s development of a mass spectrometry-based multi-attribute monitoring (MAM) method for quality control (QC) testing of therapeutic nanobodies. MAM, using LC–MS, enables simultaneous tracking of multiple product quality attributes (PQAs), offering detailed insights into protein variants and enhancing the reusability of historical data. This method is positioned as a more informative and efficient alternative to traditional high performance liquid chromatography (HPLC)–UV techniques. Nys outlined key aspects of method development, including optimization of chromatographic and mass spectrometric conditions, as well as sample handling. He then detailed the challenges and considerations involved in transferring this approach into a GMP-compliant QC setting, including method validation, risk analysis, and bridging with legacy assays. Nys emphasized that the MAM method enhances understanding of product modifications while maintaining regulatory compliance, proposing it as a transformative tool in biopharmaceutical QC environments.
A talk with a rather long title—Going Micro: Pharmacokinetic Insulin Profiles Obtained from Microsampled Rat Plasma and a Microflow LC–MS/MS Assay Result in Higher Sensitivity and Statistical Power, Less Trauma Imposed on Animals, and Fewer Animals Used Compared to a Conventional Approach—was presented by Nikoline Juul Nielsen on behalf of a team from the University of Copenhagen and Novo Nordisk, Denmark. Nielsen discussed how microsampling combined with a microflow LC–MS/MS assay can significantly improve pharmacokinetic (PK) analysis in preclinical insulin studies. Unlike traditional sparse sampling, which requires pooling data from multiple animals, microsampling enables complete PK profiles from individual rodents, reducing animal use and stress in line with the 3Rs (Replacement, Reduction, Refinement). Nielsen highlighted how a miniaturized LC–MS/MS setup (1 µL/min flow, 0.1 mm i.d.) achieved a 47-fold sensitivity increase compared to conventional systems, allowing quantification of insulin degludec in very low plasma volumes. Despite reduced sample preparation, results from micro- and conventional samples were consistent (p = 0.89). Importantly, individual profiles revealed significant inter-animal variation (p = 0.0023), demonstrating that pooled data may misrepresent treatment effects. The study advocates for broader adoption of microsampling in PK studies to improve data quality and uphold ethical standards in animal research, according to Nielson
