State-of-the-art of process development, scale-up and design for downstream processes is described for complex mixtures in biotechnology. The focus is on fermentation broth and plant-based extracts to derive methodological arguments. Academic and industrial approaches are discussed with an assessment based on some process relevant criteria. Examples of monoclonal antibody, insulin and penicillin production processes are chosen to develop a sound argumentative basis. Demands of total process integration, accuracy and sensitivity of phenomena, resulting e.g. in miniaturization of laboratory experiments and linked with necessary in-depth modeling are developed and implemented. Specific tasks of unit operation are displayed and their integration into an efficient process sequence is demonstrated. Based on that, further research needs are pointed out and corresponding activities are identified. For instance, the transfer of well established methods in chemical engineering like process modeling in combination with laboratory scale experiments and final miniplant validation should be followed consequently also in biotechnology applications. Some drawbacks in academic education and industrial training as well as organizational structures are discussed to help address this issue.