Prof. Dr. Christian Frech Discusses: “Breaking the Bottleneck…”

We’re all aware that higher and higher titers are coming from upstream processes – 1-5g/L is not uncommon and some processes can reach 10g/L.  Unfortunately, this increase in productivity isn’t counterbalanced by equivalent productivity improvements in chromatography processes.

Chromatography is a low throughput technique with limited flow rates.  If we have high volumes to process, we can increase the number or size of columns and build additional capacity but cost limitations and the fixed size of a plant may prevent use of this option.

If we think about the resin themselves, there is a physical limit for optimizing the binding capacity of the stationary phase.  Small increases in binding capacity or speeding mass transport can help, but won’t achieve the needed 10-fold increase in productivity.  I’m confident, however, that we can solve the productivity challenge by intensifying and optimizing processes and materials we currently use to at least partially overcome the chromatography bottleneck.

Use of continuous chromatography rather than batch processes and multi-column techniques may be useful but we don’t have a definitive answer yet.  The regulations surrounding these techniques and the process of running them are more complicated as well. Other techniques such as crystallization, precipitation, and two phase extraction are certainly being considered and integrated but can’t substitute for chromatography.

What might be interesting is to look at processes used to purify large volumes of blood plasma from complex samples.  Perhaps we borrow some approaches such as cone fractionation and precipitation and apply these to monoclonal antibodies.


1 Comment for this entry

Marcel Raedts
December 4th, 2011 on 5:25 pm

I do agree speed is one of the bottlenecks in Chromatography.
However I would like to stress it is not all to blame on “chromatography”.
Rather seldom we encounter groups who actually challenge the practically available throughput of a column. Too often real throughput advantages currently available are not exploited at all.

Nice initiative.!

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