29 May Subvisible particle formation under mechanical and interfacial stress: A case study using bovine serum albumin as a model for biotherapeutic proteins
Improving Our Understanding of the Mechanisms Behind Protein Aggregation in Biologics
The stability of protein treatments, such as enzyme replacements and monoclonal antibodies, is an ongoing challenge in modern medicine. Using the model protein BSA, we methodically analyze the role of different mechanical and interfacial stresses in the formation of subvisible particles (SVPs).
The Importance of This:
SVPs may reduce the effectiveness of drugs and trigger immunological reactions. Under the same recirculation settings, our analysis directly compares five stress modalities, pure shear, mixed shear + extensional flow, acoustic cavitation, laser cavitation, and simple foaming, despite shear stress being traditionally thought of as the primary culprit.
Main Results:
– Extensional flow outweighs shear. The introduction of multiple contraction-expansion sections resulted in bigger particles and approximately 1.6 times more SVPs compared to high shear alone.
– Most of the cases include cavitation. Laser-induced cavitation, characterized by explosive bubble bursts and shock waves, produced nearly double the number of SVPs compared to ultrasonic cavitation and foaming.
– You can’t do without surfactants. Polysorbate 80 tightened particle-size distributions and decreased SVP counts by 70% across all stressors.
Aspects Relevant to Bioprocessing:
– Streamline the processes. It is necessary to look more closely at operations like filtering, filling, and pumping that put extensional strains on the system.
– Pay close attention to areas of cavitation that are causing problems. Even minor cavitation events (e.g., in autoinjectors or dropped vials) can dramatically boost particle formation.
– Make drug compositions better. The use of surfactants strategically is still an important line of defense against aggregation caused by stress.
In order to produce safer and more stable protein treatments, our work quantifies and ranks these stresses, which gives a clear roadmap for designing more robust manufacturing and delivery procedures.
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