The production of recombinant proteins and vaccines is a rapidly growing field in biotechnological industry. Manufacturing of biologicals is a complex task ranging from strain development and upstream processing to the purification and formulation of the product. At the beginning of the biotechnology era product concentrations in bioreactors were within the mg per liter range. Currently, yields of up to 10 g per liter of fermenter harvest are obtained in monoclonal antibody production. These achievements have been mainly accomplished by the use of high expression cell lines, media optimization, and an increase in cell numbers using appropriate cultivation conditions. However, while bioreactor yields were improved significantly, optimization of downstream processing was often neglected and now constitutes a bottleneck in various manufacturing processes.
Downstream processing often accounts for the major part of production costs of pharmaceuticals. This is mainly due to the high demands on purity, removal of contaminants and product safety. In order to develop efficient processes it is not only necessary to improve existing purification methods and to introduce new unit operations but also to design complete downstream processing trains.
Currently, our research group focuses on the development of novel applications and techniques for the purification of virus particles (influenza virus, Vaccinia virus), virus like particles as well as downstream processing of pharmaceutically relevant glycoproteins (erytropoetin, factor VIII). Furthermore we investigate the aggregation behavior of macromolecular biological components and virus particles. An overview of the different activities is given below.
Our work on downstream processing of influenza virus aims at the exploration and development of a purification process for cell culture-derived inactivated whole virus vaccines. Unit operations like ultrafiltration, size-exclusion, ion-exchange, affinity, and hydrophobic interaction chromatography are combined to an overall process train. To improve performance and productivity of the DSP we focus on the use of modern resins, membrane adsorbers and monoliths as well as continuous methods like simulated moving bed chromatography.
Smallpox vaccines (Michael Wolff; OvGU Collaboration)
The current downstream process project for smallpox vaccines aims at the development of purification schemes for chicken embryo fibroblast cell-culture derived Modified Vaccinia Ankara virus (MVA-BN®). The process trains are based on a combination of pseudo-affinity MA, ion-exchange MA, HIC, and diafiltration steps. Pseudo-affinity MA are based on sulfated carbohydrates like heparin and cellulose-sulfate, whereas sulfated cellulose MA are developed and produced in our laboratories.
 Wolff M. W, U. Reichl, Expert Review of Vaccines 2011, 10, 1451-1475.
 Wolff M. W., U. Reichl, L. Opitz, 2010, US 2010/0093059 A1
 Wolff M. W., C. Siewert, S. P. Hansen, R. Faber, U. Reichl, Biotechnol. Bioeng. 2010, 107, 312-320.
 Wolff M. W., C. Siewert, S. Lehmann, S. Post Hansen, R. Djurup, R. Faber, U. Reichl, Biotechnol. Bioeng. 2010, 105, 761-769
 Post-Hansen S., R. Faber, U. Reichl, M. W. Wolff, A. P. Gram, 2010 US 2010/0119552 A1.
 Kröber T. A. Knöchlein, K. Eisold, B. Kalbfuß-Zimmermann, U. Reichl, Chemical Engineering & Technology 2010, 33, 941-959
 Opitz L., J. Hohlweg, U. Reichl, M. W. Wolff, J. Virol. Methods 2009, 161, 312-316
 Opitz L., S. Lehmann, U. Reichl, M. W. Wolff, Biotechnol. Bioeng. 2009, 103, 1144-1154
 Opitz L., A. Zimmermann, S. Lehmann, Y. Genzel, H. Lübben, U. Reichl, M. W. Wolff, J. Virol. Methods 2008, 154, 61-68
 Kalbfuss B., A. Knöchlein, T. Kröber, U. Reichl, Biologicals 2008, 36, 145-161. B. Kalbfuss, D. Flockerzi, A. Seidel-Morgenstern, U. Reichl, J. Chromatogr. B 2008, 873, 102-112.