This invention relates to a breakthrough in the art of chromatography allowing 1) larger scale of operation; 2) faster processing time; 3) disposability; 4) reduction of media/resin expenses; and 5) a reduction of capital equipment investment. In this invention, the chromatography column is replaced by a module that consists of two or more interconnected tangential flow filters and static mixers. The chromatography resin flows through this module in a single pass, while similar operations to a regular chromatographic process are performed on the resin (binding, washing, elution, regeneration, and equilibration). The buffers for these operations are pumped into the module in a countercurrent direction to the flow of resin, and permeate solutions from later stages are recycled back into previous stages. This creates concentration gradients in the permeate solutions of the tangential flow filters in the countercurrent direction to resin flow, thus saving buffer volume and increasing process efficiency.
The present invention is a system for continuous, single-pass countercurrent tangential chromatography having multiple single-pass modules. A single-pass binding step module is used for binding product from an unpurified product solution with a resin slurry. A single-pass washing step module is used for washing impurities from the resin slurry. A single-pass elution step module for eluting an output of the washing step module is used as purified product solution. A single-pass regeneration step module is used for regenerating the resin slurry. In the current invention, the resin slurry flows in a continuous, single-pass through each of the single-pass modules, and one or more of the single-pass modules comprise two or more stages with permeate flow directed countercurrent to resin slurry flow within that single-pass module. The present invention replaces conventional column chromatography and may be made disposable.
High Efficiency Continuous Countercurrent Tangential Negative Chromatography
A system, module and method for continuous or batch single-pass countercurrent tangential chromatography are disclosed for bind/elute and negative chromatography applications. The system includes binding, washing, elution (for bind/elute), regeneration, and equilibration single-pass modules. The resin slurry flows in a continuous single pass at steady-state through each module, while corresponding buffers flow countercurrent to the slurry facilitating efficient product and impurity extraction. The module and system include retentate pumps for better process robustness and control. A resin tank configured to be reversibly isolated from the single-pass modules facilitates a closed and disposable system. The method includes receiving unpurified product solution and resin slurry, isolating the resin tank, binding product (bind/elute) or impurities (negative) to the resin slurry, washing impurities from the resin slurry, eluting and capturing pure product from the resin slurry (bind/elute), regenerating the resin slurry following elution, and providing buffer solutions to all of the single-pass steps.
Name / Title
Company / Classification
Phones & Addresses
Oleg Shinkazh Principal
Chromatan Mfg Pharmaceutical Preparations
200 Innovation Blvd, State College, PA 16803 85 Needham St, Dedham, MA 02026 (617)5290784
Dl Thurrott Apr 2005 - Oct 2009
Downstream Processing Engineer
Chromatan Apr 2005 - Oct 2009
President and Chief Executive Officer
Milliporesigma 2000 - 2004
Development Engineer Ii
Education:
Northeastern University 1995 - 2000
Bachelors, Bachelor of Science, Chemical Engineering, Engineering
Skills:
Purification Chromatography Downstream Processing Biotechnology Filtration Validation Biopharmaceuticals Technology Transfer Commercialization Protein Purification V&V Protein Chemistry Fda Aseptic Processing Gmp Ultrafiltration R&D Life Sciences Pharmaceutical Industry Process Simulation Lifesciences Vaccines