Bachem peptide purification using continuous chromatography

As a leading CDMO for peptides and oligonucleotide manufacturing, Bachem has become a pioneer in the use of continuous chromatography to meet the challenge of sustainable large scale purification of oligonucleotides.

Bachem’s progress in establishing large-scale Multicolumn Counter-current Solvent Gradient Purification (MCSGP) with accompanying control strategies and workflows is a significant step in maintaining its position as a preferred partner in oligonucleotide production.

Scaling up oligomers

Purification can form a significant bottleneck in large-scale manufacturing of the oligonucleotide-based APIs that have gained significant ground within the biopharmaceutical industry over the past five years. Oligomer-based drugs originally used to treat rare diseases are now being developed to target more common diseases and larger patient populations, with approval of a first-in-class siRNA for cholesterol reduction forming just one example.

As oligo-based therapies show potential to treat millions of patients annually, this has fueled demand for larger batch sizes and commensurate increased manufacturing capacity.

However, this trend has run into a roadblock: the challenge of developing large scale manufacturing processes that are also environmentally friendly and therefore sustainable.

Currently, the manufacturing process involves high solvent consumption and generates significant waste, particularly during the purification step, which is critical in ensuring the final product is pure and free of contaminants. This has limited large-scale production of promising new oligonucleotide therapeutics.

In peptide and oligonucleotide manufacturing, chromatography has been seen as the most efficient purification method, but it can result in high waste and material consumption, as well as long running times in large-scale production. Therefore, maximizing yield and quality while ensuring sustainability is critical in API production as it helps to improve efficiency, reduce costs and meet industry standards.

Bachem innovation

In order to remain a preferred development and manufacturing partner for pharmaceutical companies in the  large-scale production of oligonucleotide APIs, Bachem needed to:

• Reduce environmental impact by reducing solvent consumption and waste during purification
• Improve efficiency with higher throughput and productivity to accelerate manufacturing
• Increase yield with target purity

Continuous processes offer particularly effective solutions to the challenges of maximizing yield and quality while ensuring sustainability in large-scale production. Accordingly, Bachem recognized continuous chromatography as a promising purification solution due to its high productivity, improved selectivity, and reduced costs.

MCSGP continuous chromatography

Bachem has implemented the world’s first Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) system for center-cut purification on an industrial scale. This technology represents a major advance in the downstream processing of oligonucleotides. It typically results in higher capacity with lower solvent consumption and higher yield compared to conventional single-column batch purification.

Bachem acquired its first two process-scale MCSGP systems in 2021 for the purification of peptides and oligonucleotides. Its systems are qualified for GMP use and have been used to that level for purifications at industrial scale.

MCSGP is a scalable, cost-effective, and highly efficient process, particularly for large-scale production, as it operates 24/7 through an automated system, reducing purification cycle times. It is also a more sustainable process, reducing solvent consumption and process mass intensity. The use of standard chromatographic conditions in MCSGP does not affect the quality of the API, making it a technology that improves the capacity, quality, and sustainability of the purification process.

Resources

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