Membrane fouling is linked to reversible or irreversible accumulation of macromolecules and solids on membrane surfaces and to the irreversible adsorption inside pores. If reversible accumulation can be controlled by filtering in subcritical conditions, then adsorption could also be minimized by reducing the soluble organic matter [extracellular polymeric substances, soluble microbial products (SMP)]. This research shows how the choice of operating parameters related to biological reaction (solid retention time and the organic loading rate) can influence the process rate and the by-product (SMP) production. It also illustrates how suspension characteristics and membrane aeration can influence membrane fouling control according to the hollow fiber configuration and to the different scales of observation. The investigations were based on the definition of different fouling level and fine-tuning of a model to better understand the effects of operating parameters on membrane bioreactor filtration.