Continuous bioprocessing in single-use bioreactors: Beyond stirred tank- based solutions

Continuous bio-processing opens up new possibilities for single-use concepts. Several mammalian cell culture processes are operated in continuous operation using perfusion technologies to not only ensure product quality and avoid product degradation, but also to reduce costs and working volumes. In combination with single-use bioreactors, the effects on production costs are even higher. The introduction of single-use bioreactors in continuous operation for microbial applications also reduces the costs of producing microbial molecules, e.g. if previously rarely used co-cultivation systems are applied. Although mainly limited to mammalian cell culture processes, single-use bioreactor concepts have been developed that are also suitable for microbial processes. In addition to stirred tank reactors, two-dimensional rocking bioreactors are well suited for fed-batch and continuous cultivation processes, since no dynamic parts have to be integrated into the bag. Whether for cell cultures or microbial processes, the robustness of the bag material and the quality of the sensors must be ensured during the longer process times in continuous cultivation. Classic electrochemical electrodes, in this case hybrid sensors of a disposable and a reusable part, can be an option to achieve long-lasting operation without compromising data quality. In addition, it is obvious that continuous processes require specific and appropriate monitoring tools to meet regulatory requirements and to detect process disturbances as quickly as possible to adjust dilution rates and product separation cycles. Therefore, the latest advances in optical density measurement and single cell analysis in combination with single-use bioreactor concepts are presented. Some examples are shown of how the construction of a single-use bioreactor including monitoring tools (on line and in line) enables continuous processes with a suitable robust control option in the case of cell culture and microbial cultivation processes. Finally, a cost estimate is made for a specific biosimilar production process to demonstrate the potential of suitable continuous bioprocessing with a single-use bioreactor and downstream processing compared to alternative, conventional concepts. Literature 1. Junne S, Solymosi T, Oosterhuis N, Neubauer P. Cultivation of cells and microorganisms in wave-mixed disposable bag bioreactors at different scales. Chemie-Ingenieur-Technik. 2013;85(1-2). doi:10.1002/cite.201200149. 2. Junne S, Neubauer P. How scalable and suitable are single-use bioreactors? Curr Opin Biotechnol. 2018;53. doi:10.1016/j.copbio.2018.04.003

Assessment of technological options and economical feasibility for cyanophycin biopolymer and high-value amino acid production

Major transitions can be expected within the next few decades aiming at the reduction of pollution and global warming and at energy saving measures. For these purposes, new sustainable biorefinery concepts will be needed that will replace the traditional mineral oil-based synthesis of specialty and bulk chemicals. An important group of these chemicals are those that comprise N-functionalities. Many plant components contained in biomass rest or waste stream fractions contain these N-functionalities in proteins and free amino acids that can be used as starting materials for the synthesis of biopolymers and chemicals. This paper describes the economic and technological feasibility for cyanophycin production by fermentation of the potato waste stream Protamylasse™ or directly in plants and its subsequent conversion to a number of N-containing bulk chemicals

Plant cell culture technology in the cosmetics and food industries : current state and future trends

The production of drugs, cosmetics, and food which are derived from plant cell and tissue cultures has a long tradition. The emerging trend of manufacturing cosmetics and food products in a natural and sustainable manner has brought a new wave in plant cell culture technology over the past 10 years. More than 50 products based on extracts from plant cell cultures have made their way into the cosmetics industry during this time, whereby the majority is produced with plant cell suspension cultures. In addition, the first plant cell culture-based food supplement ingredients, such as Echigena Plus and Teoside 10, are now produced at production scale. In this mini review, we discuss the reasons for and the characteristics as well as the challenges of plant cell culture-based productions for the cosmetics and food industries. It focuses on the current state of the art in this field. In addition, two examples of the latest developments in plant cell culture-based food production are presented, that is, superfood which boosts health and food that can be produced in the lab or at home