ABSTRACT
Anion exchange (AEX) products are commonly used as a polish step in product flow-through (FT) mode to bind impurities. Comparing
resins with membranes and membranes to membranes is challenging due to the complicated and unique scale-down model formats
of the products offered by different vendors. A novel approach to AEX FT using a short, 5 cm length, packed bed format with
a faster operating flow rate is explained. The performance of commonly used AEX resins and membrane adsorbers, detailing dynamic
binding capacity performance, efficiency, and a new disposable option for packed bed chromatography are compared. The data
presented will show that a high performance AEX resin competes well with the performance of membranes. It provides similar
processing times and the added benefits of reusability, ease of packing at different scales in various column formats, and
the ability to implement initial process design from early phase manufacturing to commercial manufacturing, reducing overall
costs and time to market.
AEX chromatography resins and membrane adsorbers are frequently used for downstream purification in the biotechnology industry.
AEX products are used for polish chromatography in product FT mode to bind product-related and process impurities. Multiple
product formats are commercially available, including chromatography resins, which are packed into chromatography columns,
and membrane adsorbers, which are supplied in self-contained plastic housings. Comparing performance across product types
and formats, including resins to membranes and membranes to membranes, is challenging due to the complicated and unique formats
for scale-down models of the different product types.
In FT mode, membranes have shown advantages over traditional soft gel packed beds due to faster operating flow rates, reduced
buffer requirements, and disposability. In most cases, traditional soft-gel FT columns are sized for the optimization of volumetric
throughput to improve operating flow rate and decrease process bottlenecks, rather than sized for actual impurity binding
capacity. This results in packed columns with larger diameter, and therefore volume, than optimal, and this improper column
sizing results in greater resin requirements and increased buffer usage, both of which impact operating time and cost of goods.
Although membranes may be simpler to implement for early phase manufacturing, where the process scale is typically smaller,
these products are not always cost effective at the larger, late phase or commercial manufacturing scales due to high material
costs and lack of reusability. In addition, the available product formats are limited, posing linear scale-up challenges,
adding to the challenge of maintaining process continuity and proving process equivalence between scales. Late-phase process
redesign or a complete switch to packed bed chromatography may be required due to high consumable costs or limited product
formats not allowing for linear scale-up.
Figure 1: Pressure-flow curve for POROS HQ 50 in 8 cmD Go-Pure Pre-Packed column format at bed heights of 5 cm and 20 cm
(5 um frits, 0.1 M NaCl, system pressure subtracted).
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On the other hand, the re-use of resins is well established for traditional packed bed chromatography and this facilitates
lower overall material costs. In addition, chromatography columns are easily scalable. Unit operations can be defined and
locked for early phase manufacturing and then simply scaled up in a linear fashion as manufacturing scale increases reducing
the need for later phase redesign. High performance, rigid resins with a higher volumetric throughput capability provide an
advantage over soft-gel resins allowing for properly sized columns with smaller footprints similar to membranes. These rigid
resins allow for convective flow through the bead, improving mass transfer and increasing efficiency at higher linear flow
rates, thereby improving process productivity.
