Comparative Characterisation of Five Plasma-Derived Human Serum Albumin Preparations: Structural Integrity, Functional Properties, and Quality Attributes.

Background: Human serum albumin (HSA) is a critical therapeutic protein with widespread clinical applications. Despite standardised manufacturing protocols, quality variations between HSA preparations are poorly characterised. Objective: To comprehensively characterise five commercial plasma-derived albumin preparations (VIALEBEX®, ALBUNORM®, ALBUREX®, FLEXBUMIN®, ALBUTEIN®) using multiple analytical approaches to assess structural integrity, post-translational modifications, functional properties and purity. Methods: Ten batches in total from five manufacturers were analysed using size-exclusion chromatography (SEC) for aggregate quantification, ion exchange chromatography (IEX) for isoform profiling, surface plasmon resonance (SPR) for neonatal Fc receptor (FcRn) binding, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for protein quantification. Results: VIALEBEX® contained the highest proportion of native HSA (35.2% vs. 15.1-22.2%) and the lowest levels of oxidised forms (13.2% vs. 27.4-33.3%) despite higher polymer content. SPR demonstrated higher FcRn binding affinity for VIALEBEX®. All preparations exceeded 98% albumin purity, with varying co-purified protein profiles. Conclusions: Significant quality variations exist between HSA preparations. VIALEBEX® demonstrated greater structural integrity and functional properties despite a higher polymer content, suggesting complex quality relationships beyond simple aggregation. The preservation of structural integrity and higher redox state of VIALEBEX® could be relevant considerations when selecting a product for clinical or pre-clinical use.