Biomedical Engineering Reference
In-Depth Information
Fermentation
broth
Removal of solids
Cell disruption
(via chemical or mechanical methods)
Intermediate purification and concentration
Final product isolation
Product filtration and fill
Figure 12.6
Stages in the extraction and purification of intracellular fermentation
products.
general, the feedstock for the final polishing step is very clean, with few impu-
rities, so this step typically involves only one unit operation having both high
resolving power and high recovery. However, if the processing capability of the
chromatographic step is limited, a concentration step may be required before col-
umn loading [19]. Drug substance after the final concentration and polishing step
is ready for formulation and fill/storage. The schematic in Figure 12.7 depicts
the typical stages of recovery and purification of therapeutic products and the
methods employed during the processing steps.
12.3.4.2 Quality Risk Management for Purification Process
The major risks
associated with the extraction and purification process are discussed in the fol-
lowing section.
Inefficient Harvest/Recovery Conditions
One major risk during the manufactur-
ing process is inefficient harvesting of the product from cells. For example,
low cell culture titers (10-100 mg/l) may require the collection of large vol-
umes of product-containing HCCF that then requires rapid processing; or if the
desludge time in the centrifuge is too long or too short, it can result in low
yields of product, poor clearance of medium components from solids, or product
contamination. Other risks to the product may include degradation risk from high
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