PEPTIDES & PROTEINS
Figure 2 - Side-cut recycling
MCSGP for oligonucleotide purification by the total mass of all inputs ( raw materials , solvents , water etc .) required to produce a defined mass of desired product .
For tides , the largest contributors to the overall PMI fall mostly between the synthesis and purification stages , with the latter being very high , due to washing and water usage ( Figure 1 ). These realities make the intensification of chromatographic purification an attractive target to reduce the overall PMI of manufacturing , as well as limiting organic waste and saving resources .
PMI during the purification of complex APIs is high , mainly due to yield and purity requirements . In every purification system , there will always be a trade-off between yield and purity . For chromatography , the column load defines the Pareto curve due to band broadening , tag-along and displacement effects .
This means that in a purification step , there will always be product co-eluting with related substances . These ‘ side-cuts ’, as they are called , are fractions that contain product but are not pure enough to be processed further . By re-purifying them with the same purification conditions , overall yields can be increased significantly – by 10-30 % in our experience .
In batch processing , side-cuts need to be collected iteratively and stored . Once enough side-cut fractions have been collected , they can by pooled and run again with the same parameters . However , this batchwise recycling of side-cuts puts a strain on the manufacturing system , from storage space and solvent consumption to manpower and analytical capacity .
MCSGP : Fully automated recycling
Multi column solvent gradient purification ( MCSGP , Figure 3 ) is a continuous chromatographic technology that performs automatic side-cut recycling within the same purification system by using two chromatographic columns in counter-current mode . 3
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