The advance in the cell culture technology allows people to express antibody at higher and higher titres such as 10 – 20 g/litre or more. This production level is nearly 20 times higher than the level commonly achieved in the biopharmaceutical industry 5 years ago.

However, there is no downstream chromatography purification step to match with such a great capacity increase. The best affinity-based Protein A medium can only manage to achieve a capacity increase of 2 to 3 times (e.g. from 20 mg/ml 5 years ago to 40 – 50 mg/ml now) and it is reaching its physical limit (approx. 60 mg/ml).

The liquid volume won’t be reduced after the Protein A capture step (assuming the elution volume is 3 CV) if the antibody titre is so high. So the benefit of volume reduction factor will disappear.

Protein A affinity medium is very costly and not very robust. It always places a huge inventory burden to a biotech company. Any kind of mis-handling may mean a loss of good fortune The leaked protein ligand is another contaminant in the production stream and has to be removed by an extra chromatography step.

When the antibody is expressed in high titers (e.g. 10-20 mg/ml), the content of the impurities such as host cell proteins, host cell DNA, virus, pigments and other small nutrition molecules (e.g. growth factors and cholesterols) becomes the minority, e.g. less than 50% in comparison to the content of the target antibody).

Instead of capturing the target antibody with expensive affinity media, we propose to capture the impurities but let the target antibody passing through. It is so called negative chromatography antibody purification (N-CAP) technology. A group of ion-exchange and mixed-mode (chemical ligand) chromatography media with complimentary binding spectrums can be deployed to efficiently capture all the impurities. Such type of media is much stable and cost much less. Capacitywise, the chemical ligand media generally has much higher binding capacity as well.

If you would like to know more about how the N-CAP technology can benefit your manufacturing process, please contact us for further information.