Downstream Processing: Improving Productivity in Downstream Processing - - BioPharm International

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Downstream Processing: Improving Productivity in Downstream Processing


BioPharm International
Volume 19, Issue 11

INCREASED VELOCITY


Figure 3. A comparison of linear velocity for two anion exchangers (AIEX), one of which was designed primarily for high -flow capture steps
Improvements in resin design can be illustrated by comparing a classic fast-flow, agarose-based resin with a recently introduced resin designed to improve productivity. The increased flow velocity that can be achieved with this second-generation anion exchanger is demonstrated in an industrial column with a 20 cm bed height and a 1 meter internal diameter (i.d.). A constraint of the industrial production environment is the need to work with moderate pressures to achieve adequate flow rates. Realistically, very large columns for capture applications should not need to handle more than 1–2 bar to avoid weight and handling issues. Designing an ion exchanger for capture means striking a balance between bead properties that give high capacity and high resolution, and properties that allow high flow rates at low back-pressures. The packed bed of the new resin enables a linear flow rate of more than 700 cm/h at a back-pressure of less than 3 bar. High flow rates can improve turnaround time in downstream processing by decreasing washing, cleaning, and re-equilibration times. In most cases, sample loading and elution times can also be reduced, though this reduction depends on the properties of the target molecule and impurities. These time savings can result in the production of more batches to meet the quantity demands for high-dose biopharmaceuticals.

INCREASED CAPACITY


Figure 4. Dynamic binding capacity for bovine serum albumin in a 20 cm bed height.
High flow velocity alone does not make a productive process. Binding capacity at high speeds, however, is essential for capture steps. The second-generation resin provides significantly higher dynamic binding capacities compared to classical fast-flow agarose anion exchangers (Figure 4).

A high binding capacity of 80–120 g/L IgG (at residence times of 2–6 minutes and typical pH and conductivities) could be obtained with a novel, recently introduced cation exchanger belonging to the same high-flow agarose generation.9

OVERALL PRODUCTIVITY

By combining speed and binding capacity, overall productivity is enhanced, as seen in Figure 5, which compares high-scale productivity for the capture of a target protein from an E. coli homogenate on three different resins. This study demonstrated that it is feasible to purify more than 100 kg of target protein product in 24 hours.


Figure 5. High productivity capture from an E. coli homogenate






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