Impurities downstream processes

Ironmaking refers to those processes which reduce iron oxides to iron. By the nature of the processes, the iron produced usually contains carbon and/or other impurities which are removed in downstream processing. There are three principal categories of ironmaking processes, in order of commercial importance blast furnace, direct reduction, and direct smelting. 

Costs of downstream processing for bioprocesses are increased by 1) low concentrations of products, 2) numerous impurities at low concentration and 3) intracellular materials (if cell disruption is necessary). However, the high specificity of biocatalysts is a benefit to downstream processing since products closely related to the desired product are less likely to be present Waste products of bioprocesses are likely to be less environmentally damaging, which also reduces downstream processing costs. 

Whole-cell biotransformations frequently showed insufficient stereoselectivities and/or undesired side reactions because of competing enzymatic activities present in the cells. These side reactions can modify the substrates and/or products. Furthermore, whole-cell biotransformations are limited due to the intrinsic need to grow biomass, which generates its own metabolites that are not related to the biotransformation reactions and, therefore, which need to be removed during the downstream process. Both the cells themselves and the unrelated metabolites produced are impurities that need to be removed after the biotransformation reaction. With isolated enzymes, there are no organism and unrelated metabolites to remove after the biotransformation processes. 

In addition to protein impurities emanating directly from the source material, other proteins may be introduced during upstream or downstream processing. For example, animal cell culture media are typically supplemented with bovine serum/foetal calf serum (2-25 per cent), or with a defined cocktail of various regulatory proteins required to maintain and stimulate growth of these cells. Downstream processing of intracellular microbial proteins often requires the addition of... 

Process-related impurities Impurities that are derived from the manufacturing process. They may be derived from cell substrates (e.g., HCPs, host cell DNA), cell culture (e.g., inducers, antibiotics, or media components), or downstream processing (e.g., processing reagents or column leachables). 

TMPase acts to dephosphorylate both TMP and its precursor dUMP, forming a mixture of TdR and 2 -deoxyuridine (UdR). As a starting material for zidovudine synthesis, TdR must be essentially free of this impurity, which would pass through the manufacturing process to form a demethylated analogue of zidovudine. Separation of TdR and UdR requires difficult and costly downstream processing hence, the key to a commercial process is metabolic engineering to minimize biosynthetic UdR. 

Downstream processing may consist of several operations such as liming to precipitate the metabolite as the calcium salt, washing of the precipitate with water to remove soluble impurities, acidification using strong acids to convert the salt in its free acid form. The acidic liquor may be demineralized using IER, decolorized using active carbons, concentrated under vacuum, and finally crystallized. 

The purity of a crystalline product depends on the nature of the other species in the mother liquor from which the crystals are produced, the physical properties of the mother liquor, and the processing that occurs between crystallization and the final product (downstream processing). Impurities can find their way into the final product through a number of mechanisms the formation of occlusions, trapping of mother liquor in physical imperfections of the crystals or agglomerates, adsorption of species onto crystal surfaces, as part of chemical complexes (hydrates or solvates), or through lattice substitution. 

The selectivity of the used membranes is of large influence as well. A selectivity larger than 500 would significantly reduce the amount of impurities in the permeate stream and thereby downstream processing of the synthesis gas. 

Washing the Precipitated Oxalates. As a result of the 2500-L heel of slurry left in the precipitation tank, the product slurry contained large concentrations of contaminating cations. To yield an acceptable product for downstream processing in MPPF, these ions had to be diluted from the product. Five equal volume washes of the slurry were calculated to reduce the non-lanthanide impurity concentrations of polyvalent cations to acceptable levels only four washes are needed to reduce the monovalent cations to acceptable levels as shown in Tables 1 and 2. 

As with any other classical approach in downstream processing of proteins, the process is split into three steps a capture step, followed by a separation step, and finally by a polishing step to remove residual impurities originating from leached compounds of the sorbent and/or fragments and aggregates.72... 

The process of purification, also called downstream processing, depends on the product and the degree of purification required.74 Current strategies used for purification of therapeutic proteins generally involve these steps (1) sample preparation (clarification or extraction), (2) product capture (product concentration), (3) intermediate purification (removal of bulk impurities), and (4) polishing (removal of trace impurities) as shown in Figure 32.4. 

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