In this work was presented a sequential strategy to optimize and scale-up the production of ethanol by solid-state saccharification and fermentation using rice bran as substrate. In the first step, fermentation was carried out in Erlenmeyers to study the influence of eight variables by means of a Plackett Burman design. After the choice of most significant ones, a central composite rotational design (CCRD) for three independent variables (rice bran concentration, moisture content and inoculum size) was conceived to optimize the ethanol production in a packed-bed bioreactor. From Erlenmeyers to packed bed bioreactor the process was scaled-up 10 times. Maximum ethanol production in the packed-bed bioreactor was 135 10.8 g kg(-1) at inoculum size, rice bran concentration and moisture content of 10% v/v, 62.5% w/w and 65% w/w, respectively. The ethanol yield obtained in the packed-bed bioreactor was similar to that in the erlenmeyers flasks (138.7 g kg(-1)), validating the strategy adopted for optimization and scale-up. (C) 2016 Elsevier Ltd. All rights reserved.