Downstream bioprocessing involves many steps (ex: clarification, chromatography, filtration, etc.) to purify and concentrate a desired molecule produced by natural sources.
One of these methods, tangential flow filtration (TFF), is used in downstream bioprocessing to both:
These techniques are used in specific applications such as (but not limited to):
Unlike normal flow filtration (NFF), the feed in TFF flows parallel to the membrane instead of being pushed through the membrane. The advantage here is that in TFF, there is less of a chance for filter clogging, and it is also gentler on shear-sensitive products.
Figure 1.Normal Flow Filtration (NFF) vs. Tangential Flow Filtration (TFF)
There are many ways that TFF can be implemented in the downstream process as described below.
TFF systems for the filtration of molecules like mAbs, insulin, vaccines, and recombinant proteins have been traditionally operated for reuse. However, reuse of TFF devices requires major steps including cleaning, validation, and storage that add no value to the product, yet require significant time and labor. Single-use TFF (ex: Pellicon® Capsules) eliminates many of the steps of traditional TFF processes to reduce process complexity, save time, and conserve resources in the filtration of mAbs and other biologics.
Figure 2.Significant time reduction in a TFF process with single-use TFF as demonstrated using Pellicon® Capsules. Times may vary based on the specific application and process.
SPTFF differs from traditional batch tangential flow filtration (TFF) in several ways (Figure 2).
Traditional batch TFF requires recirculation of the feed material through the membrane module multiple times to achieve a higher concentration with each passage as the filtrate is removed.
SPTFF uses just one pass through multiple membrane modules connected in series—increasing the path length—to achieve the same volume reduction over time as the traditional batch mode. Due to the single-pass operation, there is no need to return the feed to the original tank, which in many cases can eliminate tankage altogether. Further, SPTFF is typically run at lower feed flow rates to increase conversion of feed to permeate. This allows for smaller pumps and pipe sizes, which reduce hold-up volume within the system and increases product recovery compared to batch TFF. SPTFF is also a gentler option for shear sensitive molecules as the fluid is not passed repeatedly across a membrane. To learn more about implementing and scaling SPTFF, read our technical article.
Figure 3.Traditional batch TFF recirculates feed material through the membrane multiple times while single-pass TFF uses multiple membrane modules in series for volume reduction.
These characteristics make SPTFF amenable to intensify chromatography steps by concentrating the solution before loading the column and allowing a smaller amount of resin and buffer to be used. SPTFF also allows for higher concentrated formulations compared to traditional TFF.
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