ONE-FLOW translates ‘vertical hierarchy’ of chemical multistep synthesis with its complex machinery into self-organising ‘horizontal hierarchy’ of a compartmentalized flow reactor system – a biomimetic digital flow cascade machinery with just one reactor passage. To keep horizontal hierarchy manageable, orthogonality among the consecutive reactions needs to be increased. The winning point of nature is to have invented catalytic cascades. ONE-FLOW will uplift that by enabling the best bio- and chemocatalysts working hand in hand. 4 synthetic flow cascades ('metabolic pathways’) and 1 flow cascade driven by automated intelligence ('signaling pathway') will produce 4 Top-list 2020 drugs. ‘The Compartmentalized Smart Factory’ will develop organic, inorganic, and mechanical compartmentalization. ‘The Green-Solvent Spaciant Factory’ will fluidically allow the use of interim reaction spaces (spaciants). ‘The Systemic Operations Factory’ will aim at full orthogonality using data-base guided ultimate process harmonization. ‘The Digital Machine-to-Machine Factory’ will alter the landscape of chemical synthesis by virtue of the "Internet of Chemical Things". Automated machine-to-machine data transfer enables relegation of process monitoring to central computer systems under the oversight of chemists. ‘The Fully Continuous Integrated Factory’ will develop a commercial platform technology under the auspices of sustainability-driven process-design evaluation, making amenable the new kind of processing to all chemists. ONE-FLOW has massive impact potential: i) 38 billion Euro production cost saving; ii) 300 million EUR cost saving per drug; iii) address diseases with 500 billion Euro medication costs; iv) increase market share of emerging high-tech SME players by 10% in 10 years; v) open new windows of opportunity (personalized medicine) with 200-500 million Euro per disease; and vi) achieve 40% female share on a senior scientist level (ONE-FLOW: 34% senior, 57% junior).