Process Example: Single-Use TFF Cassettes
The following economic analysis of an ultrafiltration process demonstrates the savings that can be achieved when using single-use
filtration cassettes instead of reusable ones. The analysis takes into consideration the cost of consumables, such as water,
CIP solutions, and buffer solutions, as well as labor and overhead costs associated with running a TFF process in a cGMP process.
These costs can vary from site to site, so individual site costs can be input to create a customized model.
The membrane surface area of the filtration cassettes chosen for this model was 2.5 m2, an area sufficient to process batch sizes up to approximately 1,000 L. This amount of membrane surface area typically would
be used for one ultrafiltration process step in clinical-scale production. In clinical-scale and contract manufacturing, often
only four to six batches of product are processed per campaign and then the reusable cassettes are either placed in storage
or discarded. This scenario is represented in this particular economic analysis.
Consumables, including the filtration cassettes, buffers, water, and CIP solutions used during the process, also are accounted
for in this model.
Cassette costs vary from different manufactures, so an average cost of the reusable cassettes was used. Typically reusable
cassettes cost approximately $3,600 per m2. By way of comparison, single-use cassettes are approximately 20% of the cost of reusable cassettes or approximately $800
In addition to the cassettes, various buffer solutions are used for the filtration process. Some of the buffers are used for
the membrane equilibration and diafiltration operations. More importantly, with reusable TFF, a significant amount of these
buffers are used for the CIP portion of the process. In addition to these CIP solutions, purified water is used for flushing
the reusable cassettes. These CIP solutions and the need for purified water for flushing the cassettes are eliminated when
single-use cassettes are used.
Lastly, labor and overhead costs are considered. These labor and overhead costs (also referred to as factory overhead, factory
burden, and manufacturing support costs) refer to both direct and indirect factory-related costs that are incurred when the
product is manufactured. Along with costs such as direct material, the cost of labor and overhead must be assigned to each
batch produced so that the cost of goods are valued and reported accurately. The overhead includes such things as the electricity
used to operate the factory equipment, depreciation on the factory equipment and building, factory supplies, and factory personnel
not included as direct labor. Once these costs have been tabulated, they have a significant impact on the cost of the ultrafiltration
process. Typical labor and overhead costs for a cGMP approved manufacturing facility range from $2,000 to $3,500 per hour
in the United States. In our model, we assumed this cost to be $3,500 per hour.
As mentioned above, implementing single-use cassettes can eliminate many of the non-value–added steps of pre-use and post-use
CIP and as a result the overall time of the ultrafiltration process is reduced. As a result, there is increased productivity
and the overall cost of manufacturing is reduced. This increase in productivity can be illustrated by tabulating the labor
and overhead costs associated with each process step and calculating the total cost savings per batch. Table 1 lists each
of the ten primary activities associated with a typical reusable ultrafiltration process. Table 1 also shows the reduced number
of process steps needed for a single-use ultrafiltration process. That 2.4-h reduction in processing times translates into
total savings for the process of approximately $8,400 per batch.
Table 1. Labor and facility costs, per batch and per campaign (assuming five batches per campaign) for reusable and single-use
tangential flow filitration steps, assuming an overhead cost of $3,500 per hour
After identifying the costs for membranes, water, CIP solutions, and buffer, as shown in Tables 2 and 3, we compare these
costs in Table 4. Although the cost of cassettes is higher in the single-use model, these higher membrane costs are more than
offset by the reduction of costs associated with water and buffer usage and overhead. Over the course of a five-run campaign,
the accumulated costs saving is significant in favor of single-use TFF. Figure 4 provides a graphical depiction of this overall
cost comparison of reusable and single-use TFF.
Table 2. Membrane costs