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Gentofte, Denmark

Fallet C.,TU Braunschweig | Fallet C.,NNE Pharmaplan | Rohe P.,TU Braunschweig | Rohe P.,Julich Research Center | Franco-Lara E.,TU Braunschweig
Biotechnology and Bioengineering | Year: 2010

The synthesis and secretion of the industrial relevant compatible solutes ectoine and hydroxyectoine using the halophile bacterium Chromohalobacter salexigens were studied and optimized. For this purpose, a cascade of two continuously operated bioreactors was used. In the first bioreactor, cells were grown under constant hyperosmotic conditions and thermal stress driving the cells to accumulate large amounts of ectoines. To enhance the overall productivity, high cell densities up to 61 g L -1 were achieved using a cross-flow ultrafiltration connected to the first bioreactor. In the coupled second bioreactor the concentrated cell broth was subjected to an osmotic and thermal down-shock by addition of fresh distilled water. Under these conditions, the cells are forced to secrete the accumulated intracellular ectoines into the medium to avoid bursting. The cultivation conditions in the first bioreactor were optimized with respect to growth temperature and medium salinity to reach the highest synthesis (productivity); the second bioreactor was optimized using a multi-objective approach to attain maximal ectoine secretion with simultaneous minimization of cell death and product dilution caused by the osmotic and thermal down-shock. Depending on the cultivation conditions, intracellular ectoine and hydroxyectoine contents up to 540 and 400 mg per g cell dry weight, respectively, were attained. With a maximum specific growth rate of 0.3 h -1 in defined medium, productivities of approximately 2.1 g L -1 h -1 secreted ectoines in continuous operation were reached. © 2010 Wiley Periodicals, Inc.

Johnsson O.,Lund University | Sahlin D.,Novozymes AS | Linde J.,NNE Pharmaplan | Liden G.,Lund University | Hagglund T.,Lund University
Control Engineering Practice | Year: 2015

In this study a modified mid-ranging strategy is proposed where the controller for the secondary manipulated variable uses its own output as its setpoint, possibly with an offset and/or re-scaling. This modification allows the manipulated variables to increase in unison so that the mid-ranging advantage of utilizing the fast dynamics of the primary controller to regulate the process can be achieved also in non-stationary processes, while not adding complexity to the controller. The proposed control strategy has been implemented in pilot-scale (500. l) industrial bioprocesses where it is used to control the dissolved oxygen level by manipulating agitator speed and aeration rate. The controller is demonstrated to perform well in these, outperforming a reference controller which has previously been shown to give satisfactory control performance. It is also shown in similar experiments that the strategy can easily be adapted to control dissolved oxygen in bioprocesses where the feed rate is controlled using an extremum-seeking controller. The proposed strategy is generally applicable to non-stationary processes where a mid-ranging approach is suitable. © 2015 Elsevier Ltd.

Beregovykh V.V.,Moscow State University | Spitskiy O.R.,NNE Pharmaplan
Vestnik Rossiiskoi Akademii Meditsinskikh Nauk | Year: 2013

Innovation development of pharmaceutical industry is close connected to knowledge transfer going to each subsequent life cycle phase of medicinal product. Formal regulation of technology and knowledge transfer is essential for achievement high quality during production of medicines designed during development phase. Conceptual tools, approaches and requirements are considered that are necessary for knowledge and technology transfer across all the life cycle phases of medicines. They are based on scientific knowledge of medicinal products and take into account both international and Russian regulations in the area of development, production and distribution of medicines. Importance of taking into consideration all aspects related to quality of medicines in all steps of technology transfer is shown. An approach is described for technology transfer organization for Russian pharmaceutical manufacturers based on international guides in this area.

NNE Pharmaplan | Entity website

NOVO NORDISK, DENMARK New aseptic filling facility with built-in flexibility We are providing all engineering services to Novo Nordisks new aseptic filling facility, which entails built-in flexibility and some of the newest technology in insulin filling. Read the full case story

NNE Pharmaplan | Entity website

MECHANICAL ENGINEER Xiao Hong "I joined NNE Pharmaplan in 2006. When I first joined, I worked as a draughtsman and about two years later I advanced to assistant mechanical engineer ...

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