Product recovery and purification

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. 

Recovery nd Purifica.tion. The production of EH Lilly s human insulin requires 31 principal processing steps of which 27 are associated with product recovery and purification (13). The production process for human insulin, based on a fermentation which yields proinsulin, provides an instmctive case study on the range of unit operations which must be considered in the recovery and purification of a recombinant product from a bacterial fermentation. Whereas the exact sequence has not been pubUshed, the principle steps in the purification scheme are outlined in Figure la. 

Fig. 1. (a) Process flow sheet for human insulin production, recovery, and purification (12) (b) corresponding steps in recovery of biosynthetic human... 

In a chemical production process at least one of the unit operations (the chemical reactor) is the place in which chemical conversion takes place. However, the chemical upstream reactor is proceeded by a series of unit operations in which the new materials are downstream prepared (the upstream operations). After conversion has taken place, the products are operations subjected to a further series of unit operations (the downstream operations). These downstream operations include product recovery and purification steps. A typical example of a production process is illustrated in Figure 1.1. 

The majority of the processes currently used to manufacture biotechnology products employ chromatography columns as the main tool for effective product recovery and purification. The scale-up (50) and validation (51) of this vastly popular unit operation are the keys for successful implementation... 

Chlor-alkali production Electrochemical synthesis Water-organic liquid separation Organic liquid mixture separaion Fermentation products recovery and purification Cell harvesting, virus and antibody concentration Protein desalting, concentration and fractionation Blood processing, including artificial kidney Isolation, concentration, and identification of solutes and particulates... 

Fermentation is typically conducted in dilute suspension culture. The low concentration in such systems limits reaction efficiency, and the presence of particulate and colloidal solids poses problems for product recovery and purification. By circulating the fermentation broth through an ultrafiltration system, it is possible to recover product continuously as they are generated while minimizing loss of enzyme or cells and keeping product concentration in the bioreactor below the self-inhibition level for the biocatalyst. This process is referred to as perfusion. As the ultrafiltration unit is part of the production process, the entire system is often considered a membrane reactor. 

Petrides et al,15 indicate that the BioPro Designer is ideally situated to ask what if type questions. It facilitates a sensitivity analysis of the influence of key variables on the production cost and the profitability of the project. The effect of three variables were analyzed. Their analysis indicates that product cost is quite sensitive to a biomass content of 20% and less. The product cost does not change significantly for a biomass content of greater than 20%. This is because most of the production cost is associated with the product recovery and purification costs. They emphasize that this sort of information may be utilized to prioritize future work. 

The product gas from the quench is absorbed with water to recover the ACRN, HCN, and ACE. The aqueous solution of ACRN, HCN, and ACE is then fractionated and purified into high-quality products. The products recovery and purification is a highly efficient and low-energy consumption process. This ACRN technology minimizes the amount of aqueous effluent, a major consideration for all acrylonitrile producers. 

A catalytic process was designed to make 150 metric tons per year of product with a net profit of 0.25/lb of product. The catalyst for the process costs 10/lb and it takes 2 months to shut down the process, empty the old catalyst, reload fresh catalyst, and restart the process. The feed and product recovery and purification sections can be pushed to make as much as 120% of design basis capacity. The reactor section is sized with sufficient catalyst to make 100% of design basis when operated with fresh catalyst at 500°F. The reactor can be operated at temperatures only up to 620°F, for safety reasons. The reactor weight hourly space velocity (lb of product per hour per lb of catalyst) is given by the equation... 

Kennedy and Wahl on December 1A, 19 0. In September 19 2, the first pure compound of plutonium, Pu02, was prepared by Cunningham and Werner. Since that time plutonium has been studied extensively and its production, recovery, and purification have been well established. 

On the other hand, polymeric beads of supported ILs ( polymer-supported imidazolium salt, PSIS) were also prepared via the covalent anchoring of an imidazolium salt to a polystyrene resin.These PSISs, which have the advantage of significantly enhancing the nucleophilicity of metal salts compared with conventional methods, have been used as efficient catalysts for nucleophilic fiuorination and for other nucleophilic substitution reactions. In particular, the authors found that the applied PSIS had many practical merits product recovery and purification was simple and catalyst recovery and reuse were easy (Figure 4.12). 

Distillation is the baseline process for the chemical process industry, with 40,000 columns in operation in the US, handling 90-95% of all separations for product recovery and purification. The capital invested in distillation systems in the US alone is at least 8 billion [1]. 

Liquid-liquid extraction should be considered as a desirable route for product recovery and purification along with fractional crystallization and distillation. The ability to make separations according to chemical type, rather than according to physical properties such as freezing point or vapor pressure, is one of extraction s major attractions. Energy frequently can be... 

Sterilized and introduced to a bioreactor or fermenter, is typically equipped with agitators, baffles, air spargers, and sensing devices for the control of the operating conditions. A pure strain of microorganisms is introduced into the vessel. The number of cells multiplies exponentially after a certain period of lag time and reaches a maximum cell concentration as the medium is depleted. The fermentation is then stopped and the contents are pumped out for the product recovery and purification. This process is operated either by batch or continuous mode. 

Apparatus similar to that described and snitably modified to fit the char--acteristics of the readmits and products may be used with these other raw materials. In the product recovery and purification steps apparatus modifications will he more marked than in the actual oxidation step. 

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