ABSTRACT
Bio-based industries need efficient downstream solutions to process complex streams. This was addressed through a technology integration approach, where expanded-bed adsorption (EBA) is integrated with simulated moving-bed (SMB) technology. Current work involved adaptation of an SMB apparatus and control principle to implement expanded-bed level control. As an outcome, EBA-SMB technology was successfully applied for purification of γ-aminobutyric acid (GABA). This resulted in two-fold increase in productivity and a GABA purity ≥ 92 % in one step from unclarified fermentation broth, compared to ≥ 93 % purity in case of clarified broth and packed-bed SMB. These results proved that EBA-SMB technology is able to enhance process efficiency and economics of bioprocesses.
ABSTRACT
Complex streams in bio-based industries require efficient downstream processing units. Simulated moving-bed (SMB) chromatography is known to improve process efficiency by reducing resin and buffer requirement, but it can be further enhanced by technology hybridization. In the current experiments, an SMB system has been integrated with a bipolar electrodialysis (BPED) system. SMB purified γ-aminobutyric acid (GABA) from a clarified fermentation broth while BPED processed the product-containing eluent stream into recyclable eluent and purified product streams. The continuous operation did not result in any impurity accumulation.
ABSTRACT
Expanded-bed adsorption (EBA) is an efficient downstream technology that enhances the techno-economic potential of bio-based industries. However, application of EBA for bulk biochemicals requires the use of industrial resins. Therefore, two cation exchangers, namely, gel-type CS16GC and porous IRC747, were tested to purify γ-aminobutyric acid (GABA) from unclarified E. coli fermentation broth. Experiments compared the impact of gel-type and macroporous resin properties on the EBA process performance. As an outcome, the gel-type resin exhibited higher GABA binding capacity of compared to that of macroporous resin. This was due to improved hydrodynamics and uniform flow distribution in the case of gel-type resin. Further, CS16GC effectively removed ≥ 99 % of impurities and achieved ≥ 97 % GABA yield.
ABSTRACT
Vaccination is still the most efficient measure to protect against influenza virus infections. Besides the seasonal wave of influenza, pandemic outbreaks of bird or swine flu represent a high threat to human population. With the establishment of cell culture-based processes, there is a growing demand for robust, economic and efficient downstream processes for influenza virus purification. This study focused on the development of an economic flow-through chromatographic process avoiding virus strain sensitive capture steps. Therefore, a three-step process consisting of anion exchange chromatography (AEC), Benzonase(®) treatment, and size exclusion chromatography with a ligand-activated core (LCC) was established, and tested for purification of two influenza A virus strains and one influenza B virus strain. The process resulted in high virus yields (≥68%) with protein contamination levels fulfilling requirements of the European Pharmacopeia for production of influenza vaccines for human use. DNA was depleted by ≥98.7% for all strains. The measured DNA concentrations per dose were close to the required limits of 10ng DNA per dose set by the European Pharmacopeia. In addition, the added Benzonase(®) could be successfully removed from the product fraction. Overall, the presented downstream process could potentially represent a simple, robust and economic platform technology for production of cell culture-derived influenza vaccines.
