The performances of hyaluronic acid (HA) purification (yield, purity, permeate How rate and productivity) in a semi synthetic medium composed of salts, proteins/peptides by diafiltration through a 100 kDa PES membrane were studied over 10 diavolumes (DV). The HA purity went from 3% to almost 100% with a yield in the retentate close to 100% at the end of the process. The permeate flow rate showed a peculiar trend due to the influence of charged microsolutes. DF mass balance applied to three groups of solutes (HA, peptides/proteins and charged microsolutes) allowed a good prediction of HA yield and purity in the course of DF. An equation of the permeate flux based on limit flux equation, correlations between mass transfer coefficient mineral concentration and mineral mass balance was proposed to predict the process productivity. Eventually, a methodology based on these equations was proposed to predict HA yield, purify and productivity. The methodology was validated with an actual Streptococcus zooepidemicus broth. Differences between calculations and experimental performances in term of yield, purify and productivity never exceeded 10%. (C) 2015 Elsevier B.V. All rights reserved.