This type of reaction-separation integration is carried out by coupling the fer­mentation tank to a vacuum chamber that allows extracting ethanol due to its higher volatility in comparison to the rest of components of the culture broth. It has been reported that a 12-fold increase in ethanol productivity can be reached using vacuum fermentation (Cysewski and Wilke, 1977). However, for reaching this productivity, the addition of oxygen was required that negatively influenced the costs, which were already high enough due to the creation of vacuum con­ditions. Nevertheless, da Silva et al. (1999) point out that vacuum fermentation using a flash chamber coupled to the bioreactor can demonstrate better technical indexes than extractive fermentation or fermentation coupled to pervaporation (see Figure 9.8). Ishida and Shimizu (1996) proposed a novel regime for car­rying out the repeated-batch alcoholic fermentation coupled with batch distilla­tion obtaining ethanol concentrations of 400 g/L. Some examples of this type of reaction-separation integration are shown in Table 9.6.