Introduction:
A recent study conducted at the University of Kansas has found that the order in which biologic drug products are exposed to hydrodynamic shear and interfacial dilation significantly affects protein concentrations. The study showed that protein solutions subjected to interfacial dilational stress followed by pumping resulted in higher protein particle formation compared to protein formulations that were first pumped and then subjected to stress.
- Interfacial dilational stress plays a dominant role in protein particle formation.
- Protein solutions exposed to interfacial dilational stress followed by pumping resulted in higher protein particle formation than those subjected to pumping followed by stress.
- Limiting the exposure time to the air-liquid interface or removing the air-liquid headspace could decrease protein adsorption and subsequent particle formation.
- For unit operations such as ultrafiltration or diafiltration processes, multiple passes would lead to more protein particle formation, so single-pass purification steps may be considered.
- Modifying the sequences of steps in drug substance manufacturing can reduce protein formation.
Conclusion:
The order in which biologic drug products are exposed to hydrodynamic shear and interfacial dilation plays a significant role in protein particle formation. This finding has implications for the manufacturing of monoclonal antibodies and other biologics, as it suggests the need to limit exposure to the air-liquid interface and consider single-pass purification steps. Further research and optimization of manufacturing processes can help reduce protein particle formation and improve the quality of biologic drug products.
