An Economic Analysis of Single-Use Tangential Flow Filtration for Biopharmaceutical Applications

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.

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.

(NOVASEP)

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.

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

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

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.

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.

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.

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.,