472212 Effects of Histidine and Sucrose on the Physical Properties and Ultrafiltration Performance of a Monoclonal Antibody
Effects of histidine and sucrose on the physical properties and ultrafiltration performance of a monoclonal antibody
2016 AIChE Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Youngbin Baek1, Nripen Singh2, Abhiram Arunkumar2, and Andrew Zydney1
1The Pennsylvania State University, University Park, PA 16802
2Bristol-Myers Squibb, Global Manufacturing and Supply, Devens, MA 01434
Monoclonal antibodies (mAb) are currently the dominant class of bio-therapeutics, with important applications in the treatment of cancer and autoimmune disorders. Monoclonal antibodies are concentrated / formulated by ultrafiltration (UF) and diafiltration (DF) to produce the formulated drug substance. There can be significant challenges in the production of the very highly concentrated solutions (often >200 g/L) needed to deliver the appropriate therapeutic dosage by subcutaneous injection . The objective of this study was to examine the effects of buffer conditions on the physical characteristics and UF/DF performance of a mAb provided by Bristol-Myers Squibb. The mAb was characterized by its hydrodynamic radius (determined by dynamic light scattering), zeta potential, osmotic pressure, and viscosity, using buffers with different pH, histidine concentration, and sucrose (used as an excipient). UF performance was evaluated using both Pellicon 3 (C- and D-screen) and Pall Omega T-series tangential flow filtration cassettes. The hydrodynamic radius was a strong function of both the histidine and sucrose concentrations, likely reflecting the complex interactions between these species and the mAb / water [2,3]. For example, the hydrodynamic radius decreased from 6.4 to 5.6 nm as the histidine concentration increased from 10 to 250 mM, while the addition of sucrose caused a slight increase in the mAb radius. These changes in radius were correlated with changes in both the osmotic pressure and viscosity of the mAb solution, particularly in the presence of high concentrations of sucrose. The change in buffer conditions also affected the UF behavior, with the increase in viscosity causing a significant decrease in filtrate flux (at high mAb concentrations) and maximum achievable mAb concentration. These results provide important insights into the factors controlling the UF behavior of mAb products, including the impact of buffer conditions on the flux and maximum achievable protein concentration.
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