Feasibility and stability evaluation of parabens as an alternative preservative for liquid monoclonal antibody...

Preservatives are critical for preventing microbial contamination in multi-dose biologics, yet their compatibility with proteins poses a major challenge. Traditional preservatives such as benzyl alcohol are limited by instability, adsorption, and negative effects on protein stability. This study demonstrates that parabens, including methylparaben and propylparaben, are feasible alternatives in trastuzumab liquid formulations. Differential scanning fluorimetry revealed minimal impact on monoclonal antibody conformational and colloidal stability compared with conventional preservatives. Trastuzumab with parabens under stress and photostability testing was systematically characterized using micro-flow imaging, dynamic light scattering, size exclusion chromatography, ion exchange chromatography, capillary electrophoresis, microfluidic modulation spectroscopy, and ultra-high resolution mass spectrometry. Parabens did not significantly affect main peak purity, charge heterogeneity, fragmentation, or secondary structure, and only slightly increased sub-visible particles, while also being suitable for a variety of monoclonal antibodies and fusion proteins. These findings establish parabens as reliable, practical preservatives, offering a new approach to developing safer and more stable multi-dose biologics.