Robustness and feasibility study of achromatographic buffer concept

Sammanfattning

The biopharmaceutical industry is under pressure to reduce production costs while ensuring the safetyand quality of their products. One area within pharmaceutical industry that poses great potential forefficiency improvements is buffer preparation, which is both labour-intensive and requires substantialstorage space, contributing to inefficiencies in the production process. This project explores thepotential for improving buffer preparation efficiency at Octapharma´s Stockholm site by transitioningfrom traditional method of buffer preparation to in-line dilution technology. The project includes four Buffers (Buffer B, C, E and F) but focuses primarily on two buffer solutions,Buffer C and Buffer F, used in Heparin-Sepharose chromatography, a critical process in large-scalebiopharmaceutical manufacturing. This project aims to evaluate the feasibility of in-line dilution forbuffer preparation by examining the impact of mass composition errors on critical buffer parameterssuch as pH, conductivity, and stability. Experimental testing was conducted to investigate the effect ofvarying the mass ratio of different components in the buffers, and theoretical calculations were made topredict pH of a buffer. The results indicated that deviations in mass ratio up to ± 10% of phosphatecomponents had minimal impact on both pH and conductivity, suggesting that in-line dilution couldoffer greater flexibility and reliability. Changes to the mass ratio of sodium chloride had a significanteffect on the pH and conductivity of both the buffers. The theoretical calculations were accurate forBuffer C since it had the lowest ionic strength, but the model required further improvements to predictpH of high ionic strength solutions. Furthermore, the study examined the effects of different storage conditions on phosphate concentrates,revealing that aerated conditions led to a decrease in pH, which could compromise buffer quality. Anoperational assessment analysis was conducted showing that in-line dilution significantly reduceslabour hours by 92% (47.5 hours) per week, thus cutting down on operational costs and improvingoverall effectivity. The findings of this work support the conclusion that implementing in-line dilutiontechnology at Octapharma is feasible and could alleviate potential production bottlenecks, improvescalability, and reduce costs, making it a promising future approach. This shift has the potential tostreamline buffer preparation and increase the overall efficiency and cost-effectiveness of theproduction system.