The era of large-scale peptide & oligo purification with MCSGP has begun

Purification of peptides and oligonucleotides

Bachem is rapidly expanding in both capacity and capabilities across our global network to address the worldwide market needs for oligonucleotides and peptides (TIDES). Purification can be a bottleneck in TIDES production because of the enormous amounts of solvents involved. To address this challenge Bachem has set up the first continuous chromatography system for center-cut purification of peptides and oligonucleotides at industrial scale.

In a recent webinar, the experts behind this success, Dr. Ralf Eisenhuth, process chemist at Bachem and Professor Massimo Morbidelli and Dr. Thomas Müller-Späth, two of the pioneers of multicolumn counter current solvent gradient purification (MCSGP) technology, and co-founders of Chromacon AG, now part of YMC Japan, explained which developments were necessary for developing MCSGP into a standard procedure. The process established at Bachem is now able to purify up to two tons of crude peptides and 500 grams of oligonucleotides under the conditions of Good Manufacturing Practice (GMP).

Moving from batch mode to continuous production  ̶  an industry trend

Implementing this green purification technology results in an enormous reduction of solvents and process mass intensity (PMI). And it is following a trend visible in many industrial fields: moving from batch mode to continuous production and never going back from continuous to batch processes.

Continuous processing is common in most manufacturing industries. Source: Prof. Morbidelli


As Prof. Morbidelli explained the Food and Drug Administration (FDA) is also very much in favour of this transition in the peptide and oligonucleotide field.

Bachem was the first CDMO ordering MCSGP systems for large-scale manufacturing in 2020. About three tons of steel valves and pumps arrived and were installed using two 30 cm columns already available. In 2022, the system was qualified and the first ever GMP purification was performed. And the results now seen are impressive: for one molecule, the overall yield was increased by 21% and the solvent consumption reduced by 75%. In 2023, the first GMP batches of peptides and oligonucleotides were released.

Milestones of establishing MCSGP as greener technology for large-scale purification of TIDES at Bachem: after only five years of the technology platform’s introduction at laboratory scale, the first MCSGP devices for large-scale purification were installed and delivered the first GMP batches.

How does continuous chromatography or MCSGP work?

MCSGP is a fully automated system using two columns that are operated in counter current mode. It internally re-purifies side-fractions called side-cuts, while continuously eluting product fractions by changing from one column to the other. During gradient purification, weak and strong adsorbing impurities are separated from the product.  

After elution from column 1, the weak adsorbing side-cut fractions are diluted and transferred onto column 2. While the product is eluting from column 1, a new crude solution is fed onto column 2. After elution and collection of the product, the late eluting side-cut fractions are diluted and transferred onto column 2. The same elution process is then repeated with column 2.  

Benefits of continuous chromatography

  • MCSGP increases the capacity, quality, and sustainability of the purification process.
  • It is a scalable, highly efficient technology, that is particularly useful for large-scale production.
  • Using an automated system, it can run 24/7, allowing a significant decrease in purification campaign cycle times.


Ready to purify tons of TIDES with a greener, economical, and more sustainable process

According to Dr. Eisenhuth “MCSGP can fix the shortcomings of batch modes because other chromatographic conditions can be applied. He explained that “it gets rid of side-fraction handling and eliminates the need for re-chromatography. It runs very robustly due to UV-based process control, so it can be operated with minimal supervision.”

And as Dr. Müller-Späth emphasized during the Question-and-Answer session “The UV-based process control can also help balancing variations in column bed height.”

At what stage of the project life cycle should MCSGP be evaluated? “As early as possible” the experts said and further pointed out that mechanistic modelling of MCSGP can speed up the process development.

Regarding capacity, Dr. Eisenhuth stated that “we are close to two tons per year with one line. And, in our new production building at our site in Bubendorf we will be able to purify more than three tons per line.” He also pointed out and that Bachem performed the first ever process validation at scale. “It’s finished and it shows the viability for large-scale purification.”

For the details, watch the webinar:


That is just another example how Bachem has uniquely overcome the challenges of making TIDES, using innovation to transform manufacturing processes. Being able to purify large quantities of TIDES, sustainably, means Bachem is an important part of delivering crucial drugs that patients rely on, thereby transforming their lives. ​

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