Continuous production of peptides, oligos, and large biomolecules is a growing trend finding favor with regulatory bodies for the ability of continuous manufacturing to make drugs of a higher and more consistent quality at a lower cost and thus more readily accessible. Continuous purification with chromatography is widely defined as a process that moves beyond the present batch time to runs that extend into days, weeks, or months. YMC is a pioneer in the technology that semi or continuously uses chromatographic processes to purify drug products.
YMC has supplied twin-column LPLC and HPLC “Contichrom” systems for major pharmaceutical and bio-pharmaceutical GMP suites in Europe, the USA, and Asia. These systems range from a few liters per minute to over 40 LPM purifying tonnes of advanced therapeutics. YMC is recognized as the industry leader in continuous and semi-continuous chromatography-based purification technology.
YMC has patented the industry-leading continuous purification approaches of CaptureSMB for biologics and MCSGP for peptides and oligonucleotides. Read more about these disruptive technologies below.
During the production of monoclonal antibodies, the Protein A capture step is the first important purification step. A fast capture step is critical to retaining product integrity and processing of large feed volumes in reasonable times. Novel periodic counter-current (PCC) processes are superior to batch processes, offering a significant economic benefit.
YMC/ChromaCon’s optimized two-column periodic countercurrent chromatography process (CaptureSMB) is the least complex and most effective process, allowing two to threefold faster processing. It saves up to 60% of expensive Protein A resin and buffer. Lab (Contichrom CUBE instrument) and GMP scale production systems (Contichrom TWIN LPLC) employing CaptureSMB are commercially available.
Maximizing the efficiency of affinity capture steps
CaptureSMB is a twin-column periodic countercurrent (PCC) process used for the continuous purification of monoclonal antibodies (mAbs) and antibody fragments using affinity resins such as Protein A and Protein L.
This 25-minute presentation (plus 15-minute Q&A) walks through how a twin-column chromatography system works, both at the bench and production scale.
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.
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.
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.
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.
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.
Maximizing yield and purity in chromatographic polish steps with Multicolumn Countercurrent Solvent Gradient Purification
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.
Contichrom lab and field testing services
Contichrom CUBE bench top instrument
YMC Contichrom® TWIN for Peptides & Oligonucleotides
TWIN 500 LPLC Tour
YMC – What We Do
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)
Hybrid Approach to Continuous Downstream Biomanufacturing
Scale-Up of Twin-Column Periodic Counter-Current Chromatography for MAb Purification
Affinity Capture of F(ab’)2 Fragments: Using Twin-Column Countercurrent Chromatography
Purifying Common Light-Chain Bispecific Antibodies
Oligonucleotides: Current Trends and Innovative Applications in the Synthesis, Characterization, and Purification
Model assisted process characterization and validation for a continuous two column protein A capture process
Continued insights into virus clearance validation across continuous capture chromatography, Journal of Chromatography A
Comparison of batch and continuous multi-column protein A capture processes by optimal design
Model-assisted process characterization and validation for a continuous two-column protein A capture process
Virus Clearance Validation across Continuous Capture Chromatography
Increasing Capacity Utilization in Protein A Chromatography
AutomAb®: UV-based Dynamic Process Control for CaptureSMB
Twin-column CaptureSMB: a novel cyclic process for protein A affinity chromatography
Enabling High Purities and Yields in Therapeutic Peptide Purification Using Multicolumn Countercurrent Solvent Gradient Purification
Comparison of batch and MCSGP chromatography for the purification of oligonucleotides and peptides showing improvements in yield/purity through MCSGP
Contichrom CUBE bench-top FPLC – a chromatographic new tool for drug discovery and purification
Mini Webinar Library : Peptide, Oligo, DNA, and RNA Continuous Purification by HPLC MCSGP
Mini Webinar Library on mABs and rProteins by YMC TWIN Column CaptureSMB
Mini Webinar Library on mAbs and rProteins by YMC TWIN Column CaptureSMB
Multi-Column Chromatography Modeling Tool
CUBE Basics: A next gen chromatography tool
YMC Insight Center – A Virtual Tour
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