Sreenivasan, Shravan, et al. The AAPS Journal 26.1 (2024): 25.
The stability of therapeutic monoclonal antibodies (mAbs) is critical for maintaining their efficacy, safety, and shelf life. Protein degradation and aggregation pose significant challenges during manufacturing and storage. This study evaluated the efficacy of taurine, a naturally occurring amino acid, as a stabilizing excipient to enhance the physical stability of mAbs under various stress conditions.
Experimental Approach: mAb1 samples were subjected to forced degradation and stress conditions (thermal stress, photostress at 365 nm, combinations of light + H2O2, and Fe2+ + H2O2). An extensive analytical characterization was performed, and the stabilizing effect of taurine was tested across different concentrations, buffer systems, and in the presence of polysorbate 80.
Key Findings:
· Under 30 minutes of thermal stress, samples without taurine developed HMW species to a degree more than 65% higher than samples containing taurine. Formulations lacking taurine displayed larger Z-average diameters, altered protein structure, increased hydrophobicity, and reduced melting temperatures relative to taurine-containing samples.
· The stabilizing benefit of taurine persisted across varied mAb and taurine concentrations, exposure times, temperatures, buffer systems, and even when PS80 was present. The 10 mM taurine formulation already produced measurable stabilization. Taurine-containing samples produced 90% less hemolysis than samples formulated with PS80.
· After 60 minutes of oxidative and photochemical stresses (light 365 nm, light + H2O2, Fe2+ + H2O2), samples without taurine showed more than 50% greater formation of degradation products compared with taurine-containing samples.
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