In most biopharmaceuticals processes, the downstream purification is dominated by chromatographic separations, which require the preparation, holding and distribution of numerous buffer solutions. Buffer preparation is a potential process bottleneck in high-capacity situations. This paper examines the use of macroscopic modeling techniques to evaluate buffer preparation for downstream processing. Cases studies will address the challenges in buffer preparation for multi-line facilities (that share buffer prep tanks), the impact of disposable containers on the demand for utilities and the cost of goods, and the effect of changes in bioreactor titer.