The cell separation from the culture broth through tangential microfiltration to isolate poly-ribosyl-ribitol-phosphate polysaccharide (PRP), which is used in the vaccine of Haemophilus influenzue type b (Rib), represents an alternative to centrifugation. An inconvenient of microfiltration is the great amount of buffer used to diafilter the culture broth, which may dilute the product. The PRP is unstable due to various factors including concentration. To overcome this problem, an ultrafiltration system functioning simultaneously and in line with the microfiltration system concentrates the product, avoiding losses. Besides, the UF permeate stream can be recycled and used as diafiltration buffer in the microfiltration feed tank, reducing the use of buffer. Since two steps are merged into one, the time required for the global process would reduce. This study presents a mathematical model based on mass balance for a MF-UF simultaneuous system for Rib cell separation, with the objective of optimizing its conditions. This model showed fair proximity to the obtained experimental data Differences obtained in the recycle and no recycle systems indicate that the best option should be evaluated according to product characteristics. For PRP recovery, a recycle system is the most appropriate, however this model can be extended to any target molecule in such a system. (C) 2015 Elsevier B.V. All rights reserved