Modeling and prediction of excipient and pH drifts during ultrafiltration/diafiltration of monoclonal antibody biotherapeutic for high concentration formulations

Autor: Anurag S. Rathore, Vishwanath Hebbi, Anupam Shukla, Souhardya Roy
Rok vydání: 2020
Předmět:
Zdroj: Separation and Purification Technology. 238:116392
ISSN: 1383-5866
DOI: 10.1016/j.seppur.2019.116392
Popis: High concentration formulation is advantageous over conventionally used intravenous formulation. A model for the drift in the excipient concentration in the ultrafiltration/diafiltration (UF/DF) operation by including the flux of each of the species through the membrane module of the system was developed. Nernst-Planck equation was used to model the flux of the charged species, and these were coupled due to the requirement of zero electric current flow associated with the permeation of the ions. In addition, volume exclusion effect due to high protein concentration in the retentate has also been accounted for in the model. The variation of pH was also calculated using a detailed balance on the H+ ions incorporating the applicable ionic equilibrium with the concentration of relevant ions in the reservoir obtained using mass balance and permeate flux and concentration of these ions. The model was validated with the experimental data on constant volume DF and volume-reducing UF experiments on a monoclonal antibody (mAb). The exchange buffer contained histidine and sodium acetate. The model results agreed quantitatively with both the DF data at different mAb as well as exchange buffer concentrations and with the UF data for over the complete range of mAb concentrations (20–200 mg/ml) for different buffer concentrations. The model also predicted the change in the pH as a function of mAb concentration to within ±0.3 units. The model could be used for both the constant volume, buffer exchanging DF as well as the reducing reservoir volume, mAb concentrating UF operations.
Databáze: OpenAIRE
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