By Kristeena Wright, Ph.D., Linda Buck, Mark Hunter, Meredith Pesta
Biomanufacturing requires a complex and reproducible process to produce an effective biologic. The yield and quality of a biologic are highly dependent on the optimization of the downstream process. Buffers are used to maintain purification conditions and monitoring their concentrations provides assurance that they were properly prepared. The incorporation of process parameters, such as pH and conductivity, helps to maintain control of the process and prevent issues that could compromise the biologic. However, pH and conductivity measurements can be affected by environmental conditions and are not appropriate concentration measurements for all buffers (e.g. nonionic or weak electrolytes). This study compared osmolality to pH and conductivity across a wide range of concentrations of common downstream buffers. The buffer solutions were prepared gravimetrically and tested using a freezing point osmometer, pH probe and conductivity probe. The study showed that, for many solutions, osmolality is a reliable and sensitive measure of solute concentration compared to pH and conductivity. Together these process controls will help ensure optimal product quality and yield.