Biomedical Engineering Reference
In-Depth Information
suppliers are still following the traditional design of a 3D stainless steel bio-
reactor with a liner, the real breakthrough in the field comes from 2D biore-
actors that do not need an outer container and can be used horizontally, not
vertically like most 3D bioreactors. Laying down the bioreactors horizon-
tally makes the facility design compact and allows the use of smaller ceiling
heights, which adds substantially to cost savings in the facility design.
A model facility that makes the maximum utilization of disposable sys-
tems was recently constructed in Chicago.
Figure 11.1
shows the layout of
the facility to manufacture erythropoietin and granulocylte-colony stimulat-
ing factor (G-CSF), about 1 kg per year. The total square footage including
the laboratory is about 12,000 square feet; another facility that produced two
monoclonal antibodies, about 100 kg per year, required about 20,000 square
feet total for manufacturing operations (see
Figure 11.2
).
Such compact facility designs allow manufacturers to dedicate facilities or
independent suites to each molecule as done by the Chicago biotechnology
company, Therapeutic Proteins, Inc. This reduced their regulatory barriers
significantly. Similar facilities using a traditional hard-walled design would
take up at least three times more space and would cost at least five times
more to construct and furnish.
A comparison of the cost of manufacturing of biological APIs using dis-
posable systems is given in
Table 11.1
.
The cost reduction shown earlier represents the most conservative cal-
culation; with appropriate adjustments of product flow, validation cycles,
and batch sizes, it is anticipated that the cost of production in well-coor-
dinated disposable systems should not be more than 50% of the tradi-
tional cost.
It is now possible for contract manufacturing companies to establish isolated
production areas for at least one type of cell line; keeping animal cell lines in
one suite would significantly reduce their regulatory costs of compliance.
A summary of pros and cons of the two systems is given in
Table 11.2
.
Irradiation and Sterilization Validation
In many cases, microbial control or sterility is required to ensure product
purity and safety. Radiation sterilization is a common means of microbial
control and sterilization applied to single-use systems. The standard meth-
ods for validating radiation sterilization are often not clearly understood
since the industry has mostly operated on using steam sterilization; however,
a keen understanding of how irradiated components are validated is impor-
tant for regulatory filing. The standards are established by the American
National Standards Institute (ANSI), the Association for the Advancement
