Background Extraction is the method of choice for separating sensitive products. For example, it has been applied in aromatics and rare-earth metal separation. Recently, biotechnological processes entered the field of bulk chemicals and might benefit from process intensification by in situ extraction of inhibiting products, however in the presence of cells and/or aeration. This study applies reactive extraction of the polyamide monomer hexane-1,6-diamine from cell-containing medium. Results To prove technical feasibility of this reactive extraction, simulation of the extraction column based on single-drop measurements was validated at pilot-scale. Simulated results show good accordance with experimental data with an error below 20%. The extraction column was subsequently used as a bioreactor with integrated aeration and product extraction applying a four-phase system investigating the effect on drop distributions and holdup of the dispersed phases. Interestingly, aeration increased the holdup up to five-fold and decreased the mean drop size of the organic extractive phase by 30%, thereby potentially improving extraction efficiency. Conclusion The ReDrop simulation tool is capable of predicting challenging separation processes like the reactive extraction of hexane-1,6-diamine with D2EHPA diluted in oleyl alcohol from a biotransformation medium. The process design enabled four-phase operation of the column with aeration, extractive organic phase and cell-containing continuous aqueous phase. (c) 2018 Society of Chemical Industry