For a system of bioethanol purification based on extractive distillation, this work addresses the problem of determining the better control configuration and the systematic tuning of the PI controllers in a framework of physical insight. The purification system is a distillation column train consisting of a preconcentration column, a dehydration column and a entrainer recovery column. To establish the control loops, a parameter called Operability Index (OI) was proposed and applied. All possible control loops were evaluated, and unlike typical works, also impurities in the product streams were considered as control outputs. The outcomes suggested that less control effort is achieved by controlling impurities than controlling purities; this means, the OI for impurities were lower than the ones for purities, and the control configuration was easily established by choosing loops of small OI. In the next step of tuning the linear PI controller for each loop, an approach of stable pole assignment was followed. Through this technique, all controllers were tuned simultaneously, and the values of the controller gains were calculated directly from the static gains and a pseudo time constant identified for every loop; this pseudo time constant corresponds to the best first order dynamics matched to the dynamics of the control output with respect to unit change of the control input. Through simulations in Aspen Plus Dynamics®, the performance of controlling impurities was illustrated and compared with the one of controlling purities, and the simultaneous tuning of controllers was demonstrated.