The following report with recommendations is the result of an expert panel meeting on soft sensor applications in bioprocess engineering that was organized by the Measurement, Monitoring, Modelling and Control (M3C) Working Group of the European Federation of Biotechnology ‐ Section of Biochemical Engineering Science (ESBES). The aim of the panel was to provide an update on the present status of the subject and to identify critical needs and issues for the furthering of the successful development of soft sensor methods in bioprocess engineering research and for industrial applications, in particular with focus on biopharmaceutical applications. It concludes with a set of recommendations, which highlight current prospects for the extended use of soft sensors and those areas requiring development.

Here, we have studied the setup of an integrated bioprocess for the production of artificial Malaria vaccine candidates with Pichia pastoris. Production of pharmaceutically relevant proteins such as vaccines has high demands regarding protein processing in the bioreactor and for subsequent purification. To implement this challenging protein expression process, a highly instrumented bioreactor was configured for repeated fed batch cultivations and supplemented with an at‐line monitoring of the target protein production via HPLC. The integration of a fast in situ purification of the sensitive products using an expanded bed adsorption for a sequential integrated bioprocess allows cyclic product separation. Thus, a fully automated production of artificial malaria vaccines was achieved.

Devices and methods for Integrated Bioprocessing have been developed for production of recombinant proteins with the yeast Pichia pastoris. In doing so cross flow filtration techniques for cell separation and product concentration are connected directly to high instrumented cultivation processes. These are equipped with on‐line measuring techniques for substrates and products, e.g., glycerol, methanol and pyruvate as well as recombinant proteins, e.g., the chemokines 1–8del MCP‐1 and vMIP‐II. Complex automation structures allow for process development at virtual plants which can be used as the basis for establishing and implementing fully automated real processes. Experiments for determination of reaction kinetics, optimization of productivity in high‐cell density cultures and Integrated Bioprocessing are outlined, along with detailed illustration of the realization of the methods at industrial pilot plant scale.

No abstract

Background: The overall aim of the interdisciplinary research project "PharmCycle" is to reduce the contamination of the aquatic environment with antibiotics by developing sustainable antibiotics, improving the environmental risk assessment of antibiotics, and reducing the discharges of antibiotics in the wastewater outlet. An overview of the holistic approach and first results are given. Results: The first step is to design sustainable antibiotics, which are effective against target organisms but, after their use, are less toxic, and are rapidly and completely degradable. To develop sustainable antibiotics, two different approaches (subprojects) are applied within PharmCycle: First, a redesign of the existing antibiotics with chemical and in silico methods ("Benign by Design"). Second, sustainable peptide-based antibiotics are produced with biotechnological methods. In the second step, the environmental risk assessment for antibiotics in the framework of the authorization process and for monitoring purposes is improved. There is a lack of data for the environmental risk assessment of antibiotics on the European market. With more transparency of these data, the environmental risk assessment for active substances and for the class of antibiotics can be improved. The aim is to increase the data availability by applying the Aarhus convention and by providing legal access to environmental information. Beside other shortages in the environmental risk assessment required by the European legislation, the effects of antibiotics directly applied in marine aquacultures are not assessed by marine prokaryotic test systems. Therefore, a marine cyanobacteria test was developed, which is more sensitive to selected priority antibiotics than the marine eukaryotic algae test (DIN EN ISO 10253) required by the European Medicines Agency. Marine cyanobacteria are of high importance for the nitrogen cycle and primary production. Moreover, they seem to play an important role with respect to climate change. To reduce the emission of antibiotics used as human pharmaceutical products to the aquatic environment, the third step focusses on the main pathway, the wastewater. Investigations to improve the wastewater treatment of