Biomedical Engineering Reference
In-Depth Information
Summary
Companies have to weigh a lot of issues when making decisions regarding
their use of disposable technologies, some of which are economical, while
others are technical or regulatory in nature. Faced with these issues, the
engineers who implement new technologies at biopharmaceutical manufac-
turing companies often face pushback from corporate management. There
are technical reasons why companies have not opted to implement dispos-
able technologies, such as when manufacturing solutions are available for
mammalian cell cultures. Disposable bags are not practical if one is using
Escherichia coli
or yeast because the biomass levels are so high that mixing,
oxygenating, etc., are not easy with current disposable technology. This has,
however, recently changed with sparged 2D flex reactors (
www.mayabio.
There are also limitations with disposable centrifuges for harvesting the
product after fermentation. Customers generally implement new technolo-
gies after they are truly tested and well proven.
Another technical issue that can delay the acceptance of disposable
solutions is scale. Many of these disposable solutions cannot be scaled
up to the very large scale that the manufacturers want. So, when grow-
ing mammalian cell cultures in Wave bags, the maximum scale is 500 L,
which is fine, but if one wants to scale up to 2,000 L or 10,000 L, one would
have to invest in much more hardware. For example, some bag solutions
for bioreactors combine all the advantages, being both ready-to-use and
readily disposable. They use a rocking table for mixing and require very
little handling and intervention. They are ideal when one wants to make
a process really lean in terms of logistics, installation, preparation, lack of
cleaning, dismantling, turnaround, etc. This is certainly a dynamic area in
terms of available products, but bag solutions at a larger scale (up to 2,000
L) require more hardware and handling, such as supportive bag-holders,
internal mixers, and other components, making the whole system more
complex and less plug and play or unplug and throw away. One loses the
level of containment, and one has a lot more handling, introducing risks
and being less amenable to lean approaches. However, for many appli-
cations, smaller scales are enough, and bags offer speed and flexibility
beyond what steel can deliver.
Smaller companies find single-use technologies attractive because they
can be set up quickly with reduced capital requirements and operated in
a relatively inexpensive lab space to produce a drug under current Good
Manufacturing Practices (cGMP) conditions. Single-use technologies
are powerful strategic tools for smaller companies who need to advance
their early stage drugs to Phase 2 or even Phase 3 clinical trials before
partnering for market approval and commercial manufacturing. Single-
use technologies allow promising new drug candidates to move through
