{"id":786,"date":"2025-11-17T11:34:29","date_gmt":"2025-11-17T11:34:29","guid":{"rendered":"https:\/\/chromocan.test\/technology\/mcsgp\/"},"modified":"2026-05-12T14:57:41","modified_gmt":"2026-05-12T12:57:41","slug":"mcsgp","status":"publish","type":"technology","link":"https:\/\/www.chromacon.com\/en\/technologies\/mcsgp\/","title":{"rendered":"Continuous Polishing (MCSGP)"},"content":{"rendered":"
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\n TWIN-COLUMN POLISHING <\/p>\n \n

\n MCSGP<\/strong> Continuous Polishing Chromatography\n <\/h1>\n \n
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Recover what batch chromatography leaves behind.<\/strong> MCSGP is the twin-column preparative HPLC process that breaks the purity\u2013yield trade-off in reversed-phase and ion-exchange polishing \u2014 same resin, same buffers, no chemistry change. With AutoPeak\u00ae dynamic process control, MCSGP delivers manufacturing-grade reproducibility on the Contichrom\u00ae platform, validated at GMP scale in peptide and oligonucleotide manufacturing.<\/p>\n

Validated across 4 PPQ runs: 99.2%<\/strong> Purity | \u221296%<\/strong> In-process controls | 235 h<\/strong> unattended operation | +9%<\/strong> Yield gain<\/p>\n

Source: Eisenhuth & M\u00fcller-Sp\u00e4th, Processes 2025 (Bachem Bivalirudin PPQ campaign, Open Access)<\/em><\/strong><\/p>\n<\/div>\n <\/div>\n <\/div>\n\n

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\n Request a Webinar<\/span><\/a><\/span> <\/div>\n
\n Download the PPQ Paper<\/span><\/a><\/span> <\/div>\n <\/div>\n <\/div>\n <\/div>\n\n
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\n The Purity-Yield Trade-off <\/h2>\n \n
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Every gradient polishing step faces the same constraint. A tight centre-cut achieves target purity \u2014 but discards product in the early and late fractions flanking the peak. Widening the cut recovers that product \u2014 but fails the purity specification. Storing side fractions and reprocessing them with additional batch runs only improves yield at a massive cost: it multiplies handling steps, analytical burden, buffer consumption, and campaign time.<\/p>\n

This is not a method development failure. It is an inherent limitation of single-column batch chromatography. When your product and its impurities are closely-eluting, no fractionation strategy can simultaneously maximize both purity and yield on a single column.<\/p>\n <\/div>\n \n <\/div>\n\n

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\n MCSGP Changes the Constraint <\/h2>\n \n
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MCSGP (Multi-column Counter-current Solvent Gradient Purification) does not optimise the cut \u2014 it eliminates the trade-off by continuously recycling the impure side-fractions rather than discarding them.<\/p>\n

Two identical columns operate in a coordinated cyclic process. While one column elutes, the other regenerates and loads fresh feed in parallel. The early-eluting and late-eluting impure fractions \u2014 the side-cuts that batch processes collect, pool, store, and reprocess \u2014 are instead transferred directly from the first column to the second column with in-line dilution, ready to re-adsorb and be re-separated in the next switch. Product never leaves the system unless it is pure. The result is that high yield and high purity are achieved simultaneously, in a continuous automated process.<\/p>\n

Because MCSGP operates with the same gradient as your existing batch polishing step, there is no change to resin, buffers, or eluent composition. Your batch method is the starting point.<\/p>\n

The performance gains are quantified across multiple validated industrial applications. Bachem AG and Bristol Myers Squibb have both published results across peptide and protein applications.<\/p>\n <\/div>\n \n <\/div>\n\n

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\n 10\u201350% <\/h2>\n \n

\n Absolute yield increase at target purity
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\n 75% \u2193 <\/h2>\n \n

\n Solvent reduction vs. batch process
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\n Zero <\/h2>\n \n

\n Re-chromatography runs, internal recycling replaces pooling
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\n 5 days \u2192 24h <\/h2>\n \n

\n Campaign time (peptide API), Bachem, GMP production scale
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Bachem AG peptide API manufacturing<\/a>, Eisenhuth, R.; M\u00fcller-Sp\u00e4th, T. Processes, 2025, (Open Access)<\/a>, Weldon, R. et al. J. Chromatogr. A, 2022 (Open Access). <\/a>\u00a0Weldon, R. et al. Org. Process Res. Dev., 2025 (Open Access).<\/a><\/em><\/p>\n\n \n <\/div> <\/div>\n<\/div>\n\n\n

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\n How MCSGP Works <\/h2>\n \n
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Each MCSGP cycle consists of two switches, with one elution from each column per cycle. Within a switch, four phases run in sequence:<\/p>\n\n\n\n\n\n\n\n\n
Phase<\/th>\nUpstream column<\/th>\nDownstream column<\/th>\n<\/tr>\n<\/thead>\n
P1 – Elution start<\/strong><\/td>\nGradient started; weakly adsorbing impurity (W) removed<\/td>\nRegeneration completed; preparation for loading<\/td>\n<\/tr>\n
P2 – Weak recycling<\/strong><\/td>\nColumns interconnected; early low-purity fractions (W\/P) transferred to downstream column with in-line dilution for re-adsorption<\/td>\nReceives recycled W\/P fraction + binds product<\/td>\n<\/tr>\n
P3 – Product collection<\/strong><\/td>\nPure product (P) center-cut collected<\/td>\nFresh feed loaded<\/td>\n<\/tr>\n
P4 – Strong recycling<\/strong><\/td>\nLate low-purity fractions (P\/S) transferred to downstream column with in-line dilution for re-adsorption<\/td>\nReceives recycled P\/S fraction + binds product<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

At the end of the switch, the two columns exchange positions by valve switching \u2014 no physical movement \u2014 and the cycle repeats. The process reaches a cyclic steady state within 1\u20132 cycles, at which point product quality and yield are consistent from cycle to cycle.<\/p>\n

In-line dilution during the recycling phases (P2 and P4) lowers the eluotropic strength of the transferred fraction, ensuring the recycled product re-adsorbs onto the downstream column rather than passing through. The dilution factor is calculated automatically by the MCSGP Wizard from the batch chromatogram.<\/p>\n

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The MCSGP Process Principle (.pptx)<\/p>\n <\/div>\n <\/div>\n <\/section>\n\n<\/section>\n\n

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Method Design with the MCSGP Wizard<\/h2>\n

MCSGP methods are designed in the MCSGP Wizard<\/strong> in ChromIQ\u00ae 9 \u2014 a tab-based interface that takes a batch chromatogram from the Contichrom\u00ae CUBE and guides you through to a complete, ready-to-run method.<\/p>\n <\/div>\n \n

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\n Step 1 \u2014 Load the batch chromatogram and enter fraction data <\/h3>\n
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Load the single-column batch design run from the CUBE directly into the wizard. Select the UV channel to use for phase boundary setting. Enter purity and concentration data from offline fraction analysis of the batch run (optional but strongly recommended). The wizard displays predicted batch yield, purity, and product loss based on the loaded chromatogram as a reference.<\/p>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n

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\n Step 2 \u2014 Define section boundaries by drag-and-drop <\/h3>\n
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Drag five vertical boundary markers on the batch chromatogram to define the four MCSGP zones: weak recycling start (t2), product collection start (t3), product collection end (t4), and strong recycling end (t5). The wizard updates predicted yield, purity, and product loss in real time as you move the markers \u2014 no manual calculation required. In-line dilution requirements for the recycling phases are calculated automatically from the boundary positions.<\/p>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n

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\n Step 3 \u2014 Configure washing, regeneration, and AutoPeak\u00ae <\/h3>\n
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Set column washing and regeneration steps in the Washing & Regeneration<\/strong> tab. Activate AutoPeak\u00ae process control in the “AutoPeak Process Control”<\/strong> tab \u2014 each of the four phase transitions (t2\u2013t5) can be activated independently. For early development runs with well-defined conditions, fixed timing is sufficient. For scale-up and extended manufacturing campaigns, AutoPeak\u00ae is essential for maintaining consistent yield and purity as conditions drift. See Dynamic Process Control \u2192<\/a> for full configuration guidance.<\/p>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n

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\n Step 4 \u2014 Review performance prediction and generate <\/h3>\n
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The Method Settings & Performance<\/strong> tab shows predicted process performance \u2014 productivity (g\/L\/h), solvent requirement (L\/g), column loading (g\/L), and pool concentration \u2014 before initiating the MCSGP run. Set the number of cycles for the main method and review the buffer volumes per pump inlet. Hit Save: the wizard generates a complete method package including Startup, Main, Shutdown, and Clean methods, plus a procedure file that loads them in the correct sequence. Open the procedure in ChromIQ\u00ae and run MCSGP.<\/p>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n\n \n

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