Biomedical Engineering Reference
In-Depth Information
the disposable nature of disposable systems, contamination is less of a con-
cern (especially cross-contamination for multihost, multiproduct facilities).
Disposable systems were first accepted by process development and pro-
duction groups for toxicology studies and early stage clinical trials. As com-
mercially available systems become more robust and reliable, disposables
have been incorporated into process platforms by many manufacturers, and
more commercial production facilities now use these technologies as an inte-
gral part of their manufacturing processes and of their efficiency and pro-
ductivity improvement tools.
The most significant change in the disposables environment has come in
the form of disposable bioreactors. With lower capital investment, ease of
operations, and portability, they are likely to replace stainless steel stirred-
tank bioreactors. Flexible containers will come with presterilized assemblies
such as ports, filters, and sensors for storage of buffer and product interme-
diates. Buffers or media can be prepared in bags for midscale operations,
which can be further simplified with predispensed chemicals. These appli-
cations will enable closed processing in most unit operations, and process
changeover will be measured in hours instead of days as required in conven-
tional facilities. Eliminating the testing requirements in changeover would
alleviate concerns of cross-contamination for multiproduct facilities. The
financial advantages would further become evident as companies would be
able to own a multitude of bioreactors that could be connected together to
form a larger batch size (a patent of the author) obviating the need to scale-
up and validate several batch sizes and, instead, invest money in doing a
good job at Process Analytical Technology (PAT) qualification.
Although disposable technologies have delivered success in develop-
ment laboratories and GMP production suites, challenges and improve-
ment opportunities yet remain. For example, concerns with extractables
and leachables have not been fully resolved even though they have been
addressed in detail. System integrity issues could lead to contaminations or
loss of product. Product quality consistency and lot-to-lot variability pres-
ent additional challenges to wider acceptance of disposable systems. The
ongoing cost of disposables is always a problem to consider especially as the
capital cost of hard-walled systems is fully amortized; however, the general
consensus is that despite this accounting system, the disposable systems are
preferred, one reason being that newer developments and improvements
in disposable components will allow the manufacturer to always be using
state-of-the-art technology rather than be stuck with a decades-old system.
The application of disposable technologies has changed the world of man-
ufacturing, not only because it brings benefits to existing manufacturers but
also because it may lower the cost of entry for newcomers. CMOs, manufac-
turers of biosimilars, and new players from emerging markets may seek the
same advantages of disposable technologies and compete effectively in the
global market.
