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.

A Multiparticulate Delivery System for Potential Colonic Targeting Using Bovine Serum Albumin as a Model Protein

“…In this study, the theoretical BSA loading was 8.81% w/v while the actual BSA loading was 8.35% w/v, hence the loading efficiency was calculated as 94.8%, which is higher than the typical recovery rate in spray drying (46, 47). As shown in Table I, among the recovered beads, there were very few agglomerated beads (2.95%), but lots of fines (10.83%), especially between 300 to 355 microns, which suggested the potential attrition of beads during the process.…”

Next Generation Drying Technologies for Pharmaceutical Applications

“…The fact that material recovery is <100% is also an issue when considering its implementation for high‐cost therapeutics. Still, proper process design can overcome many of these limitations, highlighting the great potential of spray drying as an alternative to lyophilization that may enable continuous manufacturing …”

“…Still, proper process design can overcome many of these limitations, highlighting the great potential of spray drying as an alternative to lyophilization that may enable continuous manufacturing. 146…”

Drying of Biopharmaceuticals: Recent Developments, New Technologies and Future Direction

“…Bowen et al [7] evaluated the feasibility of spray drying several mAbs in a trehalose-based formulation using similar dryers. In the initial study, ＞95% recovery was reported for mAbs processed using MS-35.…”