Abstract
Tangential flow filtration (TFF) is a common processing step in concentration and diafiltration (buffer exchange) operations
in the downstream processing of biopharmaceutical products. Using a presanitized, disposable TFF membrane makes it possible
to reduce the number of process steps and thus reduce labor by 50% or more and reduce buffer and water usage by 75% or more.
In addition to the cost savings realized from the reduced labor and buffer usage, single-use TFF can increase productivity,
by >45% in many cases. This article outlines an economic model for comparing the costs of reusable and single-use TFF in biopharmaceutical
applications.
(NOVASEP)
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Over the last decade, the bioprocessing industry has recognized that single-use products can provide significant savings in
time, labor, and capital. As a scalable and flexible technology, single-use systems have increased production capacity, eliminated
clean-in-place (CIP) steps, cleaning validation, steam-in-place sterilization, and reduced the use of caustic chemicals and
water for injection. In addition, single-use products can reduce the risk of cross contamination between batches or campaigns.
These benefits apply to single-use tangential flow ultrafiltration as well.
Figure 1. In a typical downstream process, there are several ultrafiltration tangential flow filtration (TFF) steps following
the affinity chromatography, anion or cation exchange chromatography operations
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Tangential flow filtration (TFF) is a common processing step in concentration and diafiltration (buffer exchange) operations
in the downstream processing of biopharmaceutical products. As shown in Figure 1, typically there are several ultrafiltration
TFF steps in downstream processing, such as following the affinity chromatography, anion or cation exchange chromatography
steps.
When TFF systems are operated as clean-and-reuse systems, they typically involve 10 major process steps (setup, CIP, flush,
normalized water permeability [NWP], equilibration, processing, CIP, flush, NWP, and storage). Using presanitized, single-use
TFF membranes, however, reduces the number of process steps from 10 to four (set up, equilibrate, process, CIP).
As a result, single-use TFF can reduce labor and processing time by 50% or more. In addition, by eliminating many flush and
CIP steps, single-use TFF can reduce water, CIP solution, and buffer consumption by 75% or more. By developing an economic
model, companies can identify the costs savings associated with these reductions in labor, buffer, and water. This article
will outline such an economic model for comparing the costs of reusable and single-use TFF in biopharmaceutical applications.
An Economic Model for Single-Use TFF
Figures 2a & 2b. The percentage of time required to perform each step of a reusable tangential flow filtration (TFF) process.
Typically, only 50% of the total process time is devoted to actual processing of the product. The remaining 50% is spent in
preparing and cleaning the TFF system. In contrast, in a single-use TFF system, 80% of the total process time is devoted to
processing the product, thus increasing process efficiency.
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A typical TFF process contains basic operations that include pre-use, process, and post-use activities. Figures 2a and 2b
show the percentage of time required to perform each step. Typically, in a process based on reusable TFF, only 50% of the
total process time is devoted to actual processing of the product. The remaining 50% is spent in preparing and cleaning the
TFF system. In contrast, in a single-use TFF system, 80% of the total process time is devoted to processing the product, thus
increasing process efficiency.
Figure 3. The relationship between the number of annual process cycles and the economic benefit (percent savings) associated
with single-use tangential flow filtration (TFF) at several different process scales. Single-use TFF technology is most beneficial
at smaller scales, i.e., <5 m2. Larger-scale processes can benefit, however, when the number of annual process cycles is less than 20.
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Two key factors that affect the economics of single-use TFF are membrane area and the number of annual process cycles. Figure
3 shows the relationship between the number of annual process cycles and the economic benefit (percent savings) associated
with single-use TFF at several different process scales. As seen in the figure, single-use TFF technology is most beneficial
at smaller scales, i.e., <5 m2. Larger-scale processes can benefit, however, when the number of annual process cycles is less than 20.
