Table 2. Operating sequence for a typical disposable column
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The purpose to some extent determines both the detail and the scope of the analysis. If, for example, one wished to evaluate
the operational effectiveness of an individual operation, such as buffer preparation, then it is often appropriate to look
at the operation in isolation. It is also important, however, to consider all the affected systems. In the following example,
we compare a disposable chromatography cartridge as a replacement for a conventional chromatography column in flow-through
mode (Tables 1 and 2). This example compares the Sartobind module (Sartorius Stedim Biotech, Goettingen, Germany) with a reusable
column processing 6.5 kg of monoclonal antibody (MAb) per batch in a flow-through anion column.2
Figure 1. A comparison of the costs of the conventional and Sartobind disposable membrane chromatographic technologies, according
to four major categories: capital charges, consumables, materials, and labor.
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The simple approach would be to compare the two operations in terms of the stage throughput, labor, column costs, other consumables,
and material costs. To properly compare these two options, however, the scope of the cost model needs to be wider. It should
also address the impact on the buffer preparation and buffer hold operations and on maintenance and quality operations. It
can also raise other questions. For example, Does the disposable column need a chromatography skid? By taking a broad approach
and considering all the factors, it is possible to show the full impact of disposables. The results of our example are illustrated
in Figure 1, in which the dramatic reduction in capital and materials is evident.
Taking the analysis one step further, to understand the overall impact of disposable technologies on manufacturing costs it
is necessary to build a cost model that covers the entire manufacturing process. A comprehensive analysis makes it possible
to assess a particular technology on the overall COGS and thus helps determine whether the technology should be pursued. For
example, referring to the previous analysis, does the membrane chromatography significantly reduce overall COGS, or should
alternative technologies, such as storing buffers in bags, be pursued instead? Another benefit of a model that covers the
whole process is that if constructed correctly, it should provide a framework for "what if" analyses to examine the cost impact
of changes in
- scale of operation (e.g., bioreactor volumes and titers)
- process options and improvements (e.g., changes in materials, efficiencies, titers)
- suppliers
- cost assumptions.
WHICH UNIT OPERATIONS PROVIDE THE GREATEST SAVINGS
When assessing the impact of disposables on manufacturing costs, it is interesting to consider that for a stainless-steel
MAb manufacturing operation at large scale, most of the capital investment is in support infrastructure (e.g., preparing buffers,
media, utilities, clean-in-place [CIP], and steam-in-place), followed by the bioreactors and then by downstream processing.
Based on some capital breakdown figures presented in 1999, these areas amounted to about 52%, 32%, and 16%, respectively of
capital investment.3 In addition, if one considers that most (between 55% to 85%) of the water used in a stainless-steel biotech facility relates
to cleaning reusable equipment (i.e., CIP), then it follows that technologies that reduce the extent of the support infrastructure
(e.g., buffer and media preparation and the holding of buffer media and product-containing solutions) will reduce overall
costs. Based on capital dominance, one would expect the technology with the next largest impact to be bioreactors. Therefore,
one can propose the technologies with the most potential to reduce MAb operating costs to be:
1. holding bags and associated fluid management
2. mixing systems for solution preparation (non-aseptic)
3. bioreactors.
The most mature technology listed above is item 1. The benefits of fluid-handling technologies have been demonstrated in practice,
with data in recent papers showing that if the scale fits, storing solutions and products in disposable bags can significantly
reduce both operating and capital costs.4 For example, operating costs can be reduced by about 17% and capital costs by about 40% (based on a 1,000-L scale perfusion
MAb process).5
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