Spray Drying of Monoclonal Antibodies: Investigating Powder-Based Biologic Drug Substance Bulk Storage

Abstract

Biologic drug substances (DSs) are stored and transported as frozen bulk in various containers, each having disadvantages. We evaluated a powder-based bulk storage approach based on spray drying and demonstrate for the first time that monoclonal antibodies (mAbs) can be spray dried with >90% powder collection yield using a laboratory-scale spray dryer, which outperformed three benchtop units in yield and water content reduction. Cyclone design was critical to collection yield, which remained sensitive to sample formulations. High yield was achieved for three mAbs formulated at a 2:1 mAb: trehalose weight ratio. Increasing the amount of trehalose beyond this ratio decreased yield by increasing the amount of powder retained in the drying chamber, apparently due to increased particle tackiness. Despite a high inlet temperature, the physical stability of spray-dried mAbs was comparable to or greater than that of freeze-dried counterparts. Water content of the spray-dried powder was affected more by gas residence time in the dryer than by outlet and inlet temperatures. The laboratory-scale unit, which allowed longer gas residence time, produced drier powders even at high liquid feed rate. Characterization of spray-dried mAb reconstitution time and reconstituted solution turbidity demonstrated that the process was suitable for powder-based biologic DS bulk storage applications.

Keywords:

• Biologic drug substance
• Bulk storage
• Monoclonal antibody (mAb)
• Powder collection yield
• Spray drying

Notes

NA = not applicable.

^a Chamber volume = cylinder volume + cone volume.

^b Assuming air density at 1 kg/m³.

^c Gas rate (m³/s) per chamber volume.

LS = laboratory-scale; NA = not applicable; NT = not tested because sample solutions gelled at the mesh inside the ultrasonic nozzle.

^a mAb concentration at approximately 100 mg/mL.

^b Atomizing by ultrasonic nozzle via a mesh.

^a Drying air flow rate = 0.63 kg/min = 1.39 lb/min = 76.5 g/min.

^b Assuming inlet air at 21°C and 50% RH (absolute humidity = 55 g water/lb air; i.e., 76.5 g water/min at drying air flow rate of 38 kg/h or 20.2 g water/min at 10 kg/h drying air flow rate).