This article is part of PharmTech's supplement "Bioprocessing and Sterile Manufacturing 2010."
The biopharmaceutical and vaccine industries are embracing single-use technologies more and more as alternatives to fixed
stainless-steel equipment. Although the technologies still have limitations of mass and heat transfer, the generally mild
process conditions in biopharmaceutical operations are conducive to using a disposable plastic film surface as the product-contact
layer. Disposable components also eliminate the need for surface cleaning to avoid contamination and cross-contamination.
Several factors enable the disposable plastic bags used for solution preparation, storage, and product-generation steps to
promise potential cost advantages. Because single-use systems can provide sufficient volume (i.e., currently 2000–3000 L,
depending on the application) to accommodate the capacity requirements of most commercially produced vaccine and biopharmaceutical
products (including those whose quantities have been raised by yield increases from new cell lines), the use of disposables
is posed to grow in the next decade.
As any biopharmaceutical-industry professional will probably testify, no two projects are alike. It can therefore be difficult
to make general estimates about potential cost advantages. However, when making early estimates regarding technology concepts,
it is practical and acceptable to put some rough criteria to use.
NNE Pharmaplan (Soborg, Denmark) uses a modular approach to designing and engineering processes and production facilities.
The company breaks down the project's scope into modules for structured engineering activities. Process modules are typically
combinations of process equipment (e.g., one bioreactor with three associated feed tanks) so that they can be seen as the
main building blocks of the production process.
This modular approach allows an overview of the factors that affect a project, and process modules also can be the basis for
the calculations that obtain cost-related criteria for the application of single-use technologies. Although experience has
shown that these quick estimates can be remarkably accurate, this approach is clearly rough and should only be seen as an
estimate.
Investment costs
Investment costs are probably the biggest and most obvious source of the cost advantages of single-use components over fixed,
steel systems. The difference arises mainly because single-use systems require less instrumentation and fewer utilities. Because
sterilization and cleaning processes are eliminated, installation and support systems are reduced.
This advantage clearly allows a manufacturer to purchase more capacity for a limited startup budget, but also has an effect
on the variable costs because a much lower investment sum has to be amortized, compared with that of fixed steel systems.
In fact, it is the low up-front investment cost, which lowers variables costs, that typically tips the scales in favor of
single-use systems.
Figure 1
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As seen in Figure 1, NNE Pharmaplan calculated the projected investment cost savings that single-use process modules would
provide, compared with 100% stainless steel equipment, for an upstream biopharmaceutical operation (1). Figure 1 shows that
investment cost savings of about 30% can be expected with single-use technologies, depending on the extent of their use, compared
with a full stainless steel setup. The 30% point is actually an overestimation because microbial fermentation and centrifugation
were included in these considerations, although single-use technologies are not readily available for these applications.
Recent developments such as single-use microbial fermentors from Xcellerex and single-use centrifuges from CARRCentritech
are starting to push these boundaries, however.
Area impact
Single-use systems have fewer utility requirements, and they also can be stacked or moved in certain volume ranges. These
systems thus occupy a small footprint because of their improved designs and mobility, as well as their decreased demand for
piping, valves, instrumentation, and the related maintenance space required. To be sure, single-use systems do require room
for manipulation, transport, and waste removal, but even with these space requirements, they occupy less space than do fixed
systems. To manipulate or maintain the equipment—which already occupies less space—it is possible to push the equipment aside
to allow access. In this way, the process modules can share each other's footprints to a certain degree.
Figure 2
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NNE Pharmaplan calculated the reduction in equipment footprint that could be achieved if single-use systems were installed
as process modules instead of 100% stainless steel for the same upstream area (1). Figure 2 shows that it is possible to save
about 25% of the space that a similar stainless steel installation takes, based on the extent to which single-use technology
is employed. These reductions can come from flexibility for future applications or investment-cost savings that result from
smaller building costs. Typical cleanroom cost ratios range from $3000 to $5000 per square meter. Therefore, single-use equipment
also can lower buildings' fixed costs when used in cleanroom areas.
