Initial product recovery

The sequence of process steps shown in Fig. 4 produces three batches of spent resin (a total of about 4 L) and introduces about 50 kg of LiCl into the liquid waste system. The initial product recovery steps require about two weeks of operating time, and the clean rework recovery requires another 2 weeks. 

Downstream processing for virtually aU protein biopharmaceuticals follows a fairly predictable sequence of events (outlined in Fig. 1) [17]. Following initial product recovery and concentration, multiple chromatographic steps are undertaken (usually between three and six individual fractionation steps). While gel filtration and ion exchange are particularly common, down-... 

Manufacturing approaches for selected bioproducts of the new biotechnology impact product recovery and purification. The most prevalent bioseparations method is chromatography (qv). Thus the practical tools used to initiate scaleup of process Hquid chromatographic separations starting from a minimum amount of laboratory data are given. 

The latest of three ethylene recovery plants was started in 1991. Sasol sold almost 300,000 t of ethylene in 1992. Sasol also produces polypropylene at Secunda from propylene produced at Sasol Two. In 1992 Sasol started constmction of a linear alpha olefin plant at Secunda to be completed in 1994 (40). Initial production is expected to be 100,000 t/yr pentene and hexene. Sasol also has a project under constmction to extract and purify krypton and xenon from the air separation plants at Sasol Two. Other potential new products under consideration at Sasol are acrylonitrile, acetic acid, acetates, and alkylamines. 

Product Recovery. The aHyl chloride product is recovered through the use of several fractional distillation steps. Typically, the reactor effluent is cooled and conducted into an initial fractionator to separate the HCl and propylene from the chloropropenes, dichloropropanes, dichloropropenes, and heavier compounds. The unconverted propylene is recycled after removal of HCl, which can be accompHshed by adsorption in water or fractional distillation (33,37,38) depending on its intended use. The crude aHyl chloride mixture from the initial fractionator is then subjected to a lights and heavies distillation the lighter (than aHyl chloride) compounds such as 2-chloropropene, 1-chloropropene, and 2-chloropropane being the overhead product of the first column. AHyl chloride is then separated in the second purification column as an overhead product. Product purities can exceed 99.0% and commercial-grade aHyl chloride is typicaHy sold in the United States in purities about 99.5%. 

Initially fermentation broth has to be characterised on the viscosity of the fluid. If the presence of the biomass or cells causes trouble, they have to be removed. Tire product is stored inside the cells, the cells must be ruptured and the product must be freed. Intracellular protein can easily be precipitated, settled or filtered. In fact the product in diluted broth may not be economical enough for efficient recovery. Enrichment of the product from the bioreactor effluents for increasing product concentration may reduce the cost of product recovery. There are several economical methods for pure product recovery, such as crystallisation of the product from the concentrated broth or liquid phase. Even small amounts of cellular proteins can be lyophilised or dried from crude solution of biological products such as hormone or enzymes.2,3... 

Another important argument for the use of the organic solvent is the reverse hydrolytic reactions that become feasible [61,75]. The inhibition of the biocatalyst can be reduced, since the substrate is initially concentrated in the organic phase and inhibitory products can be removed from the aqueous phase. This transfer can shift the apparent reaction equilibrium [28,62] and facilitates the product recovery from the organic phase [20,29,33]. A wide range of organic solvents can be used in bioreactors, such as alkanes, alkenes, esters, alcohols, ethers, perfluorocarbons, etc. (Table 1). 

In the context of preparing potential inhibitors of dihydrofolate reductase (DHFR), the group of Organ has developed a rapid microwave-assisted method for the preparation of biguanide libraries (Scheme 6.174) [330]. Initial optimization work was centered around the acid-catalyzed addition of amines to dicyandiamide. It was discovered that 150 °C was the optimum temperature for reaction rate and product recovery, as heating beyond this point led to decomposition. While the use of hydrochloric acid as catalyst led to varying yields of product, evaluation of trimethylsilyl chloride in acetonitrile as solvent led to improved results. As compared to the protic... 

Figure 3.9. Generalized overview of the industrial-scale manufacture of recombinant E2 classical swine fever-based vaccine, using insect cell culture production systems. Clean (uninfected) cells are initially cultured in 500-1000 litre bioreactors for several days, followed by viral addition. Upon product recovery, viral inactivating agents such as /i-propiolactone or 2-bromoethyl-iminebromide are added in order to destroy any free viral particles in the product stream. No chromatographic purification is generally undertaken as the product is substantially pure the cell culture media is protein-free and the recombinant product is the only protein exported in any quantity by the producer cells. Excipients added can include liquid paraffin and polysorbate 80 (required to generate an emulsion). Thiomersal may also be added as a preservative. The final product generally displays a shelf-life of 18 months when stored refrigerated...

The PHOSter II system is only applicable to contaminants that can be biologically degraded. In addition, it is only effective in settings where microbial activity is phosphorus limited. At sites with high contaminant concentrations, product recovery may be required during the initial treatment stage. Hydraulic conductivity and moisture content also determine the effectiveness of the PHOSter II technology. 

Since the initial work of Fraenkel-Conrat and Olcott (1945), protein esterification has been described in a number of studies (Mattarella et al., 1983 Chobert et al., 1990, 1995 Bertrand-Harb et al., 1991 Briand et al., 1994, 1995). The conventional procedure involves three steps. The first step is the mixing of reactants (protein, alcohol and acid). The second step is the esterification reaction itself, which generally ranges in length from one to several days, at 4°C. The last step is reaction termination and product recovery. 

For a product recovery of 96 percent, optimum solutions were obtained and are presented graphically via design charts. The design charts plot the optimum diafiltration volume and total time cycle as a function of other operating conditions, i.e., initial volume, recovery, membrane area and flux. For a recovery other than 96 percent, the optimum solution can be obtained using the equations developed in this paper in a similar manner. 

Although this technique is not limited to the initial cell recovery stages of a downstream process, cross-flow filtration is commonly used for product recovery operations, particularly in lower volume processes where stringent hygiene requirements apply, as in the pharmaceutical and food industries. 

Following the initial stages of product recovery from a fermentation broth, a number of purification stages will be required in all but the simplest industrial processes. In the case of high-purity pharmaceutical products, a large number of separation stages are usually required to remove all impurities from the desired final product. By identifying some difference between the product and its impurities, either physical or chemical, the desired bioseparation can be achieved. 

When the production of the secondary metabolites coincides with the death and general lysis of the cells, the recovery of the product is simply a matter of separation from the spent production solution downstream of the reactor. An example of this type of operation was initially used in Japan during the production of shikonin. However, if the secondary metabolites are stored in the vacuole of the cells and the cells remain viable but dormant during the production phase, then a permeabilizing agent such as dimethylsulfoxide (DMSO), detergents, proteins, and antibiotics may be employed in some cases in concentrations that make the cells leak product out but maintain cell viability. Success for this type of product recovery has been reported in C. roseus, Datura innoxia, and Daucus carota cell cultures. 

If the retort water is considered for domestic or irrigation uses, it would have to be treated to remove a number of contaminants. Of the major constituents in retort water, the NH4, HCOa", and organic compounds in the water clearly make it unsuitable for other uses (18). Of the trace constituents, the arsenic and selenium concentrations listed in Table IV are above the maximum permissible concentrations for drinking water (36). The boron concentration may make water unsuitable for irrigation (22). Other studies have found silver and lead concentrations in retort waters have exceeded the maximum permissible concentrations for drinking water (1,2,36). Numerous studies for the treatment of the retort water have been initiated (37). The objectives of these studies are usually to find a method to recover the ammonia and organic material from the water so that treatment costs will be lowered through by-product recovery. 

The reactor effluent must contain the net production rate of product (which is known), plus any product that is in the recycle. Recycling product to the reactor is not a good idea, as it is likely to lead to byproduct formation. A reasonable estimate of product recovery in the separation section is probably 99% or greater, so a good initial estimate of the amount of product in stream 5b is the net production rate divided by the separation recovery, or roughly 101% of the net production rate. 

Extraction of Actinides from Bismuth into Ammonium Chloroaluminate (13, 14, 15). Experiments are being performed to demonstrate the oxidative extraction of the actinides from bismuth into ammonium chloroaluminate (NHi+AlCli ) and product recovery from the latter salt. Initial experiments with uranium dissolved in bismuth showed essentially complete extraction of the uranium into the salt with only a minimum of contact time at 330°C. Extraction of thorium from bismuth took appreciably longer and the solubility of ThCl in NH4AICI4 at 375°C was appreciably less than that of UCli+ at the same temperature, (1.1 wt % ThCl vs. 7.0 wt % UC1I+). 

Further calibrations with respect to cross fault communication within hydraulic compartment II was obtained by re-entering well 7-2 2 years after the initial production test to assess formation pressure recovery relative to the initial drawdown and to perform further testing. The data acquired gave indications of partial pressure communication across intensity zones and small scale (10-20 m throw) faults in the vicinity of the well. 

Again, using the example, when the fractional product recovery is multiplied by the initial number of moles of A, one obtains a value of 0.60 ((0.70 X 0.86) X 1.00 moles of A) moles of B, as the amount of product to be expected. This is in agreement with the quantities specified in the original example, and, it will be noted, is the same as the academic yield specified on a fractional basis. Thus, we can write down the form of an additional relationship, specified in fractional terms, which is often useful in quantitative calculations which relate to industrial processes (Eq. 1.13). 

Sodium chloride, or common salt, is one of the earliest chemical commodities produced. Its production from seawater was prompted by essential dietary needs, and later for its value as a food preservative caused by the scattered accessibility of land-based sources. The word salary itself is derived from the Roman salarium, which was a monetary payment given to soldiers for salt purchase to replace the original salt issue. While the initial production and harvesting of sodium chloride was from dietary interests, food needs today represent less than 3% of consumption, and uses as a chemical intermediate far exceed this (Table 6.1). The wide availability of sodium chloride has contributed to the derivation of nearly all compounds containing sodium or chlorine from this salt, and to the establishment of many large industrial chemical operations adjacent to major salt deposits. Three general methods are in common use for the recovery of sodium chloride, which in combination were employed for the worldwide production of 225 million tonnes of this commodity in 2000 and 183 million tonnes in 1990 (Table 6.2). 

Initially, a fixed-bed reactor with no separation was tested. The reactor was packed only with the catalyst and inert filler material with no adsorbent. Further, the feed gas propene (9% by volume) was mixed with helium as a carrier. No separation via PSR operation was imposed on the reactor contents. Fig. 8 shows that the steady-state conversion of propene is significantly less than 1% (about 0.03%) and the product recovery is almost negligible. The slight time lead in simulation is due to nonaccounting of the dead time in experiments. The estimated equilibrium conversion from thermodynamics is about 24 /o based on pure propene feed. Thus, the conversion in a fixed-bed reactor is far below the equilibrium conversion. 

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