PEPTIDES & PROTEINS
During the 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 , new crude solution is fed onto column 2 . After elution and collection of the product , the late eluting ( strongly adsorbing ) side-cut fractions are diluted and transferred onto column 2 . The same elution process is than repeated with column 2 .
One technical challenge of MCSGP purification is the need to be robust towards minor disturbances of flow rate , column load , crude purity and eluent composition . In-process controls should be in place during the start-up phase of the system to ensure smooth launch into steady state . Due to the high level of automation , the systems are capable of running overnight without any supervision .
Each individual run is inherently less efficient than batch mode , but this is compensated during recycling , as the side-cuts are constantly mixed with crude product , which increases yield compared to traditional batch re-purification . Another advantage of continuous chromatography versus batch re-purification is the significantly shorter campaign time .
When it comes to solvent savings , the potential gains are often a function of the performance of the underlying batch mode , with MCSGP seeing modest gains against highly optimised batch processes , but significant solvent savings in less efficient processes . Exploring these potentials can really move the needle on pharmaceutical companies ’ sustainability targets .
Greener at scale
With MCSGP , chromatographic conditions that are not viable in batch purification – such as steeper gradients and / or using green solvents – can be applied to alleviate the shortcomings of batch-mode systems . This opens
Figure 3 – MCSGP process
the exploration space for more sustainable manufacturing . We have observed in some projects that the overall API process mass intensity could be reduced by up to 70 % while simultaneously multiplying possible manufacturing throughput . 3
Overall , continuous chromatography for tides has not yet reached innovation saturation . For example , mechanistic modelling can further speed up process development and parameter optimisation , perform robustness studies or explore the design space of operating parameters to increase yields , reduce waste and recycle solvent more efficiently .
Conclusion
The intensification of pharmaceutical manufacturing is increasingly taking place at the level of drug substance manufacturers and CDMOs . Continuous chromatography for tides is a fast , scalable , cost-effective and highly efficient purification technology compared to current batch processing methods , but it requires specialised equipment and process expertise to implement .
With MCSGP , Bachem pioneered a fully automated continuous chromatography system for largescale tide purification under GMP conditions , defining a new industry standard with strong potential to reduce solvent consumption and process mass intensity of API production . In 2023 , the company released the first GMP drug substances purified by MCSGP for both therapeutic peptides and oligonucleotides .
The era of continuous chromatography for tides has arrived . With it , pharmacutical companies and drug substance CDMOs ought to consider using efficient continuous processes with greener solvents as part of a larger sustainability strategy for tides manufacturing . ●
References : 1 : C . Challener , BioPharm International 2018 , 31 ( 4 ) 2 : L Gerstweiler et al ., Chemical Engineering Science , 2021 3 : R . Eisenhuth , Large Scale TIDES purification with MCSGP under GMP , Bachem webinar , 5 December 2023
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Dr Philipp Markolin
SCIENCE MARKETING SPECIALIST
BACHEM philipp . markolin @ bachem . com www . bachem . com
50 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981