Team Leader (DSP)

profile_image
Dr. Michael Wolff
Phone:+49 391 6754 676

Profile

Universitätsplatz 2, Gebäude 25, 39106 Magdeburg, Germany

Team (DSP)

Dr. Laura Thomas
Postdoc
Ana Raquel Fortuna
PhD Student
Laura Fischer
PhD Student
Matthias Meininger
PhD Student
Pavel Marichal-Gallardo
PhD Student
Thomas Weigel
PhD Student
Anja Bastian (maternity // parental leave)
Technical Assistant
Lisa Fichtmüller
Technical Assistant

Additional Information

Collaborations with industry:

  • BIA Separations Inc.
  • EMC microcollections GmbH
  • IDT Biologika GmbH
  • Merckle Biotec GmbH
  • Novartis Vaccines and Diagnostics GmbH & Co. KG
  • Sartorius Stedim Biotech GmbH
  • Sentinext Therapeutics Sdn Bhd
  • Tosoh Bioscience LLC

Collaborations with academia:

  • Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Chemical Engineering Program Cell Culture Engineering Laboratory (Prof. Dr. Leda dos Reis Castilho)
  • Karlsruhe Institute of Technology, Karlsruhe; Biomolecular Separation Engineering (Prof. Dr. Jürgen Hubbuch)
  • Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany; Physical and Chemical Foundations of Process Engineering Group (Prof. Dr.-Ing. Andreas Seidel-Morgenstern)
  • Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany; Physical and Chemical Process Engineering Group (Prof. Dr.-Ing. Kai Sundmacher)

Downstream Processing

Downstream Processing

Motivation

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.

<em>Fig.1. Current downstream processing activities at BPE.</em> Zoom Image
Fig.1. Current downstream processing activities at BPE.

Influenza Vaccines

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.

<em>Fig.2. Options for downstream processing in influenza vaccine manufacturing </em> Zoom Image
Fig.2. Options for downstream processing in influenza vaccine manufacturing

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.

<em>Fig.3. Options for downstream processing in smallpox vaccine manufacturing </em> Zoom Image
Fig.3. Options for downstream processing in smallpox vaccine manufacturing

References

[1] Wolff M. W, U. Reichl, Expert Review of Vaccines 2011, 10, 1451-1475.
[2] Wolff M. W., U. Reichl, L. Opitz, 2010, US 2010/0093059 A1
[3] Wolff M. W., C. Siewert, S. P. Hansen, R. Faber, U. Reichl, Biotechnol. Bioeng. 2010, 107, 312-320.
[4] Wolff M. W., C. Siewert, S. Lehmann, S. Post Hansen, R. Djurup, R. Faber, U. Reichl, Biotechnol. Bioeng. 2010, 105, 761-769
[5] Post-Hansen S., R. Faber, U. Reichl, M. W. Wolff, A. P. Gram, 2010 US 2010/0119552 A1.
[6] Kröber T. A. Knöchlein, K. Eisold, B. Kalbfuß-Zimmermann, U. Reichl, Chemical Engineering & Technology 2010, 33, 941-959
[7] Opitz L., J. Hohlweg, U. Reichl, M. W. Wolff, J. Virol. Methods 2009, 161, 312-316
[8] Opitz L., S. Lehmann, U. Reichl, M. W. Wolff, Biotechnol. Bioeng. 2009, 103, 1144-1154
[9] Opitz L., A. Zimmermann, S. Lehmann, Y. Genzel, H. Lübben, U. Reichl, M. W. Wolff, J. Virol. Methods 2008, 154, 61-68
[10] 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.

 
loading content