The absence of a systematic scale-up approach for biological conversion of cellulosic biomass to commodity products is a significant bottleneck to realizing the potential benefits offered by such conversion. Motivated by this, we undertook to develop a scale-up approach for conversion of waste paper sludge to ethanol. Physical properties of the system were measured and correlations were developed for their dependence upon cellulose conversion. Just-suspension of solid particles was identified as the scale up criterion based on experiments at lab scale. The impeller speed for just solids suspension at large scale was predicted using computational fluid dynamics simulations. The scale-up strategy was validated by analyzing mixing requirements such as solid-liquid mass transfer under the predicted level of agitation at large scale. The scale-up approach enhances the prediction of reactor performance and helps provide guidelines for the analysis and design of large scale bioreactors based on bench scale experimentation.