PEPTIDES

More Peptide. Fewer IPCs.
Continuous Polishing Chromatography with MCSGP.

Higher yield, less solvent, no re-chromatography — no purity–yield trade-off. MCSGP is the twin-column preparative HPLC process proven at commercial scale by Bachem on Bivalirudin.

Across 4 PPQ runs: 99.2% Purity | −96% In-process controls | Multi-day GMP campaigns | +9% Yield gain

Source: Eisenhuth & Müller-Späth, Processes 2025 (Bachem Bivalirudin PPQ campaign, Open Access)

Talk to Our Peptide Specialists

Download the PPQ Paper

Talk to Our Peptide Specialists

Download the PPQ Paper

The Peptide Purification Bottleneck

Peptide demand is surging — driven by GLP-1 agonists, oncology peptides, and a pipeline of 150+ candidates in clinical trials. Purification by reversed-phase HPLC is the critical bottleneck.

Conventional batch chromatography forces a painful trade-off: high purity or high yield — not both. Achieving target purity requires a narrow center-cut, discarding valuable product in side-fractions. Recovering that product means costly re-chromatography — with all the associated solvent consumption, QC testing, and campaign delays.

For high-volume APIs like semaglutide and tirzepatide, this inefficiency is unsustainable.

The Solution: MCSGP with AutoPeak® for Peptide Purification

MCSGP (Multi-column Countercurrent Solvent Gradient Purification) eliminates the purity-yield trade-off in peptide chromatography. Two identical columns continuously recycle impure side-fractions — recovering peptide product that batch processes discard. It uses the same RP and IEX resins and solvents as your existing batch peptide method.

AutoPeak® dynamic process control monitors peptide elution profiles in real-time via UV and conductivity, automatically adjusting collection windows to maintain consistent output quality — enabling robust, unattended 24/7 peptide purification.

Same chemistry. Better results. MCSGP works with the RP-C18, C8, C4, IEX, and mixed-mode stationary phases and mobile phases already used in your peptide batch process — your existing resin and solvent conditions are the starting point for MCSGP development. No change to your chromatographic chemistry is needed.

Learn About MCSGP + AutoPeak®

Proven Results: MCSGP vs. Batch – Peptide Purification

+10–50%

Yield Increase

30-75% ↓

Solvent Reduction

80% ↓

Campaign Time

Zero

Re-chromatography Runs

75–95% ↓

Fewer IPC Analyses

50% ↓

Lyophilization Volume

Commercial GMP manufacturing: Bachem AG

Bachem — a leading global peptide and oligonucleotide CDMO — integrated MCSGP into large-scale peptide API manufacturing at Bubendorf, Switzerland. The original process used 2D batch chromatography with extensive side-cut recycling (nearly 20% of all runs were side-cuts) to achieve a purity target of >99.3%. MCSGP delivered the same purity with significantly better process economics and throughput.

Results vs. batch for a production-scale peptide:

Purity: >99.3% maintained — fully comparable to batch
Material consumption (PMI) reduced 70% — from 5,700 to 1,600 kg per kg API
Processing time: 5 days → 24 hours
Lyophilization volume reduced ~50%
IPC analyses reduced ~75%
Side-cut re-chromatography completely eliminated
Crude throughput approximately 3× higher per day with 2×30 cm columns vs. equivalent batch

Source: Bachem AG — “Reducing Solvent Consumption for Large-Scale Peptide API Manufacturing” (Case Study, June 2023)

First-Ever MCSGP Process Validation Framework Published (Dec 2025)

A landmark open-access collaboration between Bachem AG and YMC ChromaCon presents the first regulatory-compliant Process Characterization (PC) and Process Performance Qualification (PPQ) approach for MCSGP — directly supporting FDA/EMA filings for therapeutics manufactured using continuous chromatography.

Molecule: Bivalirudin (20-mer synthetic peptide), PC on Contichrom CUBE 30, PPQ on Contichrom TWIN 500 with 2×30 cm i.D. columns.

PPQ campaign results (54.5 kg crude, 4 multiday runs):

Yield: 62% gross-to-gross (+5 pp vs. legacy batch); effective yield 76%
IPC burden reduced 96% (81 IPCs/kg → 3.2 IPCs/kg)
PMI reduced 73% (~5,200 → 1,400 kg/kg)
Output: 33.6 kg API at 99.2% purity across all 397 elutions

This publication provides a regulatory roadmap for any peptide or oligonucleotide manufacturer seeking FDA/EMA process validation.

Eisenhuth, R.; Müller-Späth, T. Processes, 2025, 13(12), 3950. DOI: 10.3390/pr13123950 (Open Access)

Case Study: Glucagon Purification — Batch to MCSGP

Molecule: Glucagon (29 amino acids, MW 3485 Da), crude synthetic mixture (55% chromatographic purity in feed) Equipment: Contichrom CUBE Combined (ChromaCon/YMC) Mode: RP-HPLC — Daisogel-SP-120-10-C8-Bio, 10 µm; mobile phases: ammonium acetate/ACN gradient

Parameter	Batch (25 cm column)	MCSGP (2 × 15 cm columns)
Purity	89.3%	89.2% — identical
Recovery (Yield)	71.2%	87.7% (+23% relative)
Productivity	9.9 g/L/h	6.1 g/L/h (−38%)

Key finding: MCSGP increased glucagon recovery by +23% at identical purity (~89%) — from 71.2% to 87.7% — demonstrating that even a process designed from a single batch chromatogram, with no dedicated optimisation, meaningfully improves yield. The 38% productivity reduction is an inherent tradeoff of the interconnected phases; for expensive therapeutic peptides like glucagon, maximising recovery more than compensates for this. The MCSGP process ran fully automated for 5 cycles (steady state achieved after cycle 1), illustrating the method-transfer simplicity of the ChromIQ® MCSGP Wizard workflow.

De Luca, C., Felletti, S., Lievore, G. et al. J. Chromatogr. A, 1625, 461304 (2020). DOI: 10.1016/j.chroma.2020.461304

Peptide Purification Comparison Table:

Parameter	Batch Peptide Chromatography	MCSGP with AutoPeak®
Purity-Yield Trade-off	Inherent — narrow cuts sacrifice yield	Eliminated — high purity AND yield simultaneously
Product Yield	50–80%	80–99% (+10–50% absolute)
Re-chromatography	Required for side-fractions	Eliminated — internal recycling
Solvent Consumption	High	Up to 75% reduction
IPC/QC Burden	Testing every side-fraction, every batch	75–95% fewer analyses
Campaign Duration	Days per batch	Up to 80% shorter (continuous 24/7)
Process Control	Manual monitoring	Automated (AutoPeak® UV-based PAT)
Robustness	Sensitive to drift and feed variability	AutoPeak® dynamically compensates
Operator Requirement	Requires supervision	Designed for unsupervised operation
Sustainability (PMI)	High waste and solvent intensity	Significantly improved PMI
Stationary Phase / Eluents	Standard RP / IEX	Same — no change required

The Contichrom® Platform: From Peptide Development to Production

All Contichrom systems support twin-column continuous chromatography with RP (C18, C8, C4), IEX, and mixed-mode resins used in peptide purification (particle sizes ≥10 µm). Methods scale predictably from CUBE → PILOT 300X → TWIN HPLC.

System Overview

Contichrom® CUBE

The essential platform for chromatography process development. This versatile 100-bar benchtop FPLC system runs batch, integrated batch, and continuous chromatography — including MCSGP and CaptureSMB — out of the box. Develop purification processes for mAbs, peptides, oligonucleotides, ADCs, and viral vectors, with verified scale-up at over 100× to pilot and production systems.

Contichrom® PILOT

Scale peptide and oligonucleotide purification to pilot and clinical GMP manufacturing. This 100-bar preparative HPLC system features MCSGP with AutoPeak® to eliminate the yield-purity trade-off — delivering +10–50% absolute yield increase at target purity and significantly less solvent than batch HPLC. ATEX Zone 2 / Class I Div 2 certified for organic solvents. Flow rates up to 300 mL/min.

Contichrom® TWIN HPLC

Produce peptides and oligonucleotides at commercial GMP scale. This 80-bar industrial HPLC system uses MCSGP with AutoPeak® to eliminate the yield-purity trade-off — increasing recovery to >90% while reducing solvent consumption compared to batch. ATEX Zone 2 / Class I Div 2 certified for organic solvents, and flow rates up to 36 L/min.

System Overview

Peptide Applications

GLP-1 Receptor Agonists (Semaglutide, Tirzepatide, Liraglutide)

Long-chain peptides (30–39 aa) with complex impurity profiles. MCSGP enables high-yield RP-HPLC purification at the multi-hundred-kg scale demanded by the GLP-1 market — with up to 75% less solvent and proportional upstream synthesis savings.

Short Therapeutic Peptides (e.g., Glucagon, Icatibant, Octreotide)

MCSGP consistently outperforms optimized batch processes for peptides in the 10–30 aa range. Published data on glucagon showed +23% yield at identical purity, with a straightforward one-day method transfer from batch.

Multi-Step Peptide Purification (RP + IEX / RP + RP)

Combine orthogonal peptide purification steps in a single automated 2D integrated batch workflow — or run MCSGP on the throughput-limiting step. One Contichrom system replaces multiple standalone batch HPLC units.

Peptide Impurity Isolation & Characterization (N-Rich)

ICH-required peptide impurity characterization typically takes weeks of repetitive analytical runs. N-Rich automated on-column enrichment isolates milligram quantities of target peptide impurities up to 80× faster.

Getting Started with Peptide MCSGP

See the Contichrom® platform in action before you commit, assess MCSGP suitability computationally or experimentally using your own peptide sequence and resin, develop your continuous method at lab scale on a Contichrom® CUBE, then scale to GMP production on the TWIN HPLC — the same platform behind Bachem’s first GMP-validated continuous peptide process.

See It First — Free Demo or Webinar

Not yet familiar with the Contichrom® platform? Start here. YMC ChromaCon offers no-charge demonstrations and introductory webinars tailored to your team.
- On-site in Zurich (half day, 2–4 hours): see the CUBE in person, run ChromIQ® live, discuss your peptide purification challenge with YMC ChromaCon application scientists
- Remote webinar (1–3 hours): interactive live session covering MCSGP, N-Rich®, ChromIQ® software, and the full Contichrom® ecosystem
- Sessions cover MCSGP process design, the ChromIQ® MCSGP Wizard, and scale-up to PILOT 300X and TWIN HPLC
→ Request a free demo or introductory webinar

Modeling Assessment for Peptides

Predict how MCSGP will perform on your peptide sequence before running a single continuous experiment. YMC ChromaCon builds a calibrated mechanistic model from your existing batch RP data.

Submit your linear gradient batch chromatography runs with fraction collection and analytical purity data — from any HPLC or FPLC system, no Contichrom® required
YMC ChromaCon calibrates and validates the model, simulates MCSGP operating points, and delivers a predicted batch vs. MCSGP performance comparison (yield, purity, productivity) with initial scale-up parameters
AutoPeak® dynamic control impact is included in the simulation
Typical timeline: 3–5 weeks from receipt of data; no material shipment required

→ MCSGP Process Modeling Service

Experimental Feasibility Study — Your Peptide, Your Resin

Your peptide is purified on YMC ChromaCon’s Contichrom® platform at our facility in Zurich. We reproduce your batch RP method as a benchmark and run ≥ 3 MCSGP experiments side-by-side.

Ship starting material to Zurich — typically ≥ 20× a single preparative batch run, scaled to 1 cm i.D. columns
We reproduce your analytical HPLC method, establish the batch benchmark, and run MCSGP experiments using your resin and solvent system
Deliverable: side-by-side batch vs. MCSGP comparison with real chromatographic data from your peptide and resin, plus fractions for your independent purity verification
Typical timeline: 4–6 weeks after receipt of starting material and purchase order

→ YMC ChromaCon Feasibility Studies

Develop at Lab Scale — Rent or Purchase a CUBE

MCSGP method development is performed on the Contichrom® CUBE using your existing RP resin and solvent system. Available for rental or purchase.

ChromIQ® MCSGP Wizard builds the initial MCSGP operating point from your existing batch chromatogram — first continuous run typically achievable within a day
Your current batch gradient conditions are the starting point — no new resin or method development required
AutoPeak® dynamic process control adjusts collection windows in real-time via UV and conductivity, compensating for feed variability and column aging
The CUBE also supports N-Rich® for in-process impurity profiling alongside MCSGP development — both run on the same platform

→ Contichrom® CUBE Rental Program

→ Purchase a Contichrom® CUBE

Scale to GMP Production — PILOT 300X or TWIN HPLC

The MCSGP method developed on the CUBE transfers directly to larger Contichrom® systems for pilot and manufacturing-scale production. YMC ChromaCon provides scale-up consulting and GMP documentation support.

PILOT 300X (up to 300 mL/min, 100 bar, ATEX Zone 2) for pilot-scale and clinical supply batches
TWIN HPLC for GMP production — the same platform used for Bachem’s first GMP-validated continuous peptide purification process (2022)
Scale-up is driven by column diameter — bed height, gradient conditions, and AutoPeak® control logic are preserved across scales
Four TWIN HPLC system sizes cover lab through full production scale
GMP documentation support (IQ/OQ/PQ) and scale-up consulting available

→ Scale-Up Consulting and Training

01 / 05

Ready to Upgrade Your Peptide Purification Process?

Book a CUBE Rental Register for the Continuous Chromatography Workshop

How does MCSGP improve peptide purification yield?

A: MCSGP continuously recycles the impure side-fractions that batch RP-HPLC discards — recovering peptide product without compromising purity. For production-scale peptides, Bachem reported +21% yield. Published data on glucagon showed +23%, and improvements of +10–50% are typical depending on the complexity of the impurity profile.

Does it work with my existing peptide RP-HPLC method?

Yes. MCSGP uses the same reversed-phase (C18, C8, C4), ion exchange, and mixed-mode stationary phases and eluent systems as your existing batch method. No change to your resin or buffer chemistry is needed — MCSGP process parameters are then developed from those existing conditions, typically within 1–2 weeks on the CUBE.

Which peptide types benefit most from MCSGP?

Peptides with complex impurity profiles see the largest gains — particularly long-chain GLP-1 agonists (semaglutide, tirzepatide), peptidomimetics, and multi-modified sequences. Even well-optimized short peptides like glucagon and icatibant show meaningful yield improvements.

Has MCSGP been validated for GMP peptide manufacturing?

Yes. Bachem has run GMP MCSGP peptide production since 2022 at their Bubendorf facility. A December 2025 landmark publication (Müller-Späth et al., Processes 13(12), 3950) provides the first-ever Process Characterization and PPQ framework — demonstrated on the 20-mer peptide Bivalirudin.

Can the Contichrom® also run standard batch peptide chromatography?

Yes. All Contichrom® systems support batch, 2D/3D integrated batch, and continuous modes on the same hardware. The TWIN HPLC production systems are dual-mode (MCSGP + batch) on a single skid — so you can run both processes without separate equipment.

How quickly can I transfer my peptide batch method to MCSGP?

How does AutoPeak® handle peptide process variability?

AutoPeak® monitors the peptide elution profile in real-time via UV and conductivity, dynamically adjusting collection windows to compensate for crude feed variability, column aging, and retention time drift — enabling robust, unattended 24/7 peptide purification. It has been validated as a Process Analytical Technology (PAT).

How does continuous peptide purification improve sustainability?

For peptide manufacturing, MCSGP requires up to 75% less solvent, 50% less lyophilization volume, and smaller upstream SPPS batches (from higher yield) — dramatically improving Process Mass Intensity (PMI). The FDA actively encourages this shift to continuous manufacturing for pharmaceutical APIs.

More Peptide. Fewer IPCs. Continuous Polishing Chromatography with MCSGP.