Biomedical Engineering Reference
In-Depth Information
In selecting a type of bioreactor and mode of operation, one should determine
whether the goal is to obtain a secreted product or the cells themselves. Other
issues to consider include the ease of sterilization and use, the need for automation,
the expertise required, expenses, the space required, the time and speed of the
operation, downstream processing needs, the process scalability and validation
concerns, single or multiple vessels, and the batch or continuous product.
Furthermore, using cell culture media that contain no serum or other components
of animal origin is necessary. Serum is not preferred for many reasons, including:
(1) possible introduction of contaminants and toxins such as viral particles, (2) a
component variability inherent in biological sources, which affects both quality
and performance of the final product, (3) a high cost as a raw material, and (4)
interference with purification of the final product. Also, regulatory issues with the
use of biological materials within the pharmaceutical industry are problematic;
meeting these requirements raises the final production costs. For more details on
bioreactors, refer to [3].
7.4.3 Downstream Processing
Once a product is obtained from a biosynthesis in bioreactors, the most time-
consuming and cost-intensive factor is the purification of the product. Based on
the physical and biochemical properties of the desired product and the level of
contaminating molecules from the cultivation broth, a broad range of separation
methods can be applied. If the supernatant is already cell-free and highly concentrated
with product (as it often is with membrane systems), there is a significant reduction
in downstream processing. However, for suspension cells cultured in larger batches,
supernatants must be pumped out and clarified before they can be subjected to
purification procedures. The purification process includes chromatographic and
filtration technologies.
With purification technologies, the challenge is to recover the target protein in
its active form and in high yields from other proteins found in the host organism,
as well as from the many components of the medium in which the cells were grown.
Time-dependent phenomena such as degradation, proteolysis, clipping, and cleav-
ing, which would not be significant in a small scale because of a faster processing
time, become the major problems in large-scale downstream processing. Hence,
the combination and design of the single steps are of paramount importance for
the economic process development. In the overall process design, the engineer has
to consider different aspects such as the elimination of contaminants, process scal-
ability, automation, the capacity of the production line, and regulatory compliance.
Optimization of downstream processing technologies is considered the central ele-
ment in the appropriate process design. For more details, see [4].
7.5
Preservation of Cells and Tissues
With rapid advances in the clinical diagnosis and treatment of diseases, there is
an increasing need for using cell and organ transplantation to cure diseases and
to correct genetic defects. Furthermore, more types of living cells, tissues, organs,
