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A sophisticated measurement system for at‐line determination of the main C‐source glucose, the by‐product acetate, and the N‐source ammonium for high cell density cultivations (HCDC) of Escherichia coli K12 TG1 is presented. One flow diffusion technique (FDA) system is used for glucose measurement in the range of 0.5 up to 40 gL–1 in the cultivation broth. Another FDA system detects the amount of the undesired by‐product acetate. The ammonium concentration in the range of 0.2 to 2.5 gL–1 is determined on‐line by a flow injection analysis (FIA) system. For verification purposes, an HPLC system which is also connected to the bioreactor for at‐line measurements is utilized. Several HCDC with cell densities of more than 100 gL–1 have been carried out. The courses of growth‐determining substrates have been detected at‐line. All used systems have shown an excellent compliance with off‐line measurements.

In process development and manufacturing, the biopharmaceutical industry requires high flexibility in its production facilities. These suites must be capable of producing clinical material or even drug substances for the market. Several products are manufactured in parallel or shortly after one another, which is challenging especially for the equipment. Product titers are increasing due to improved cell line performances, and personalized medicine will lead to tailor‐made drugs for a smaller group of patients. The resulting reduced upstream volumes enhance the opportunities for complete single‐use manufacturing trains. These requirements must be considered already during the design phase of the manufacturing facility. Engineering efforts have to be reduced as much as possible in order to reduce cost and timelines. Generic platform concepts for the overall process enable a shorter execution time as well as more efficient qualification procedures. In this contribution, the focus is on production processes for monoclonal antibodies (mAb) as a major product class of the biopharmaceutical industry. Two case studies introduce process platform concepts integrating single‐use equipment for an existing building and for a greenfield facility.

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: As the age of the blockbuster drug recedes, the business model for the biopharmaceutical industry is evolving at an ever-increasing pace. The personalization of medicine, the emergence of biosimilars and biobetters, and the need to provide vaccines globally are just some of the factors forcing biomanufacturers to rethink how future manufacturing capability is implemented. One thing is clear: the traditional manufacturing strategy of constructing large-scale, purpose-built, capital-intensive facilities will no longer meet the industry's emerging production and economic requirements. Therefore, the authors of this chapter describe the new approach for designing and implementing flexible production processes for monoclonal antibodies and focus on the points to consider as well as the lessons learned from past experience in engineering such systems. A conceptual integrated design is presented that can be used as a blueprint for next-generation biomanufacturing facilities. In addition, this chapter discusses the benefits of the new approach with respect to flexibility, cost, and schedule. The concept presented here can be applied to other biopharmaceutical manufacturing processes and facilities, including-but not limited to-vaccine manufacturing, multiproduct and/or multiprocess capability, clinical manufacturing, and so on.