Continuous Purification: MCSGP

Batch v. MCSGP

In batch chromatography of peptides and oligos, impure side fractions often have to be discarded to reach a certain product purity. With YMC’s patented MCSGP approach, impure product-containing side fractions are internally (automatically) recycled in a periodic closed-loop process while pure product is continuously extracted. Thereby, little product is lost, and the yield of pure product is maximized without any accumulation of impurities while retaining target purity.

High yield at target purity

MCSGP economic benefits

Multicolumn Countercurrent Solvent Gradient Purification process (MCSGP) is a continuous process operated by Contichrom lab-scale (Contichrom CUBE) and Contichrom TWIN pilot/process scale equipment. It provides significant economic benefits compared to single-column batch chromatography operated at low, medium, and high pressure. The economic benefits are derived by the achievement of significantly higher yield at target purity, lower buffer/solvent consumption, and higher productivity. Economic benefits are always obtained, not depending on products or applications, yet the more complex the separation task, the higher the benefits obtained through the MCSGP process.

Figure: Yield-purity-productivity relationship of MCSGP versus conventional batch chromatography. Single-column batch processes (blue) operate on a low productivity level without the potential for productivity gains when high yield and purity are required. MCSGP (red) operates at an optimum in 3D space, with high yield and purity at increased productivity.

Application of MCSGP for peptide and oligo purification

High performance liquid chromatography employing MCSGP provides a novel purification technology for peptides or oligos produced by chemical synthesis. MCSGP offers a step-change in efficiency compared to batch HPLC processing. With MCSGP, two identical reverse-phase columns are operated under high pressures in countercurrent mode with internal recycling of impurity-containing side fractions, extracting continuously pure product and discarding impurities without significant product loss. Peptides can be purified at preparative/production scale with a significantly higher yield without compromising target purity. The process allows an up to tenfold higher productivity with potentially 75% lower solvent consumption, providing an overall attractive economical production scenario and allowing to push the boundary of economic synthesis of long peptides.

Application of MCSGP for omega-3 EPA purification

MCSGP can purify complex biological mixtures, such as omega-3 eicosapentaenoic acid ethyl ester (EPA-EE) to a high target purity in a single purification step. Generic fish oil feed with a feed purity of 74% EPA-EE was subjected to an MCSGP process design to achieve a target purity of >97% EPA-EE. MCSGP was operated under high pressures in countercurrent mode with internal recycling of impurity-containing side fractions with docosahexaenoic acid ethyl ester (DHA-EE) as the main impurity, extracting continuously pure EPA-EE and discarding impurities without significant product loss. Five cycles of MCSGP achieved significantly improved yield at target purity (+ 250%), productivity throughput (+ 590%), and reduced solvent consumption by 75% compared to batch HPLC.

MCSGP process principle and design

The MCSGP process is the only known ternary continuous separation process that can unlock the yield-purity trade-off dilemma by providing high yield at target purity, thereby enhancing productivity.

The process eliminates the need for re-chromatography and the associated time and resources for sampling and testing. The MCSGP technology is patented by ChromaCon, and its process principle is intuitive, straightforward, and allows a high degree of automation. This is visualized in an animation of the two-column MCSGP design. A dedicated software wizard in the accompanying ChromIQ software allows for easy batch-to-continuous process design, transfer, and optimization.

YMC / ChromaCon offers customized services and expertise to companies and academics who wish to quickly advance their projects or test MCSGP capabilities before investing in a system.

MCSGP is used for:

  • Synthetic peptides
  • Oligonucleotides
  • Small molecules from fermentation or natural extractions (Stevia, flavonoids, cannabinoids, fish oil)
  • Blood plasma products
  • Recombinant proteins from microbial production
  • Complex organic synthesis products

MCSGP resources

Continuous purification of therapeutics—removing critical barriers in manufacturing by MCSGP

The challenges in the purification of oligonucleotides (including RNA/DNA) and peptides of time, cost, yield, and purity can be overcome with a technique called MCSGP.

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More Resources Related to This Topic

Application Information

Technology and Economics for the Purification of Oligonucleotides (and Peptides) by Twin-Column Continuous Chromatography

Process Intensification for the Purification of Peptidomimetics: The Case of Icatibant through Multi-column Countercurrent Solvent Gradient Purification (MCSGP)

Comparison of Multicolumn Capture Processes

Process Control and Optimization by AutomAb

Dynamic Process Control (MControl®) for Countercurrent Polish Processes (MCSGP)

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