Downstream processing overview

This chapter aims to overview the manufacturing process of therapeutic proteins. It concerns itself with two major themes (1) sources of biopharmaceuticals and (2) upstream processing. The additional elements of biopharmaceutical manufacturing, i.e. downstream processing and product analysis, are discussed in Chapters 6 and 7 respectively. 

Figure 6.1 Overview of a generalized downstream processing procedure employed to produce a finished-product (protein) biopharmaceutical. QC also plays a prominent role in downstream processing. Qualty control personnel collect product samples during/after each stage of processing. These samples are analysed to ensure that various in-process specifications are met. In this way, the production process is tightly controlled at each stage...

Figure 8.7 Overview of the manufacture of Betaferon, a recombinant human IFN-(3 produced in E. coli. The product differs from native human IFN-(3 in that it is unglycosylated and cysteine residue 17 had been replaced by a serine residue. E. coli fermentation is achieved using minimal salts/glucose media and product accumulates intracellularly in inclusion body (IB) form. During downstream processing, the lbs are solubilized in butanol, with subseguent removal of this denaturant to facilitate product refolding. After two consecutive gel-filtration steps, excipients are added, the product is filled into glass vials and freeze-dried. It exhibits a shelf life of 18 months when stored at 2-8 °C...

An overview of the steps normally undertaken during downstream processing is presented in Figure 3.16. Details of the exact steps undertaken during the downstream processing of any specific biopharmaceutical product are usually considered highly confidential by the... 

Figure 30.6 shows a typical recovery process for antibiotics, and a schematic overview of a typical downstream process in an enzyme plant is given in Figure 30.7. From these diagrams it is apparent that most recovery...

This chapter is an overview of industrial crystallization from the point of view of facilitating the downstream processes for product-quality improvement. Some aspects of process considerations, equipment as well as the advantages and limitations of the technique are also discussed. 

Autotrophic microalgae as well as heterotrophic yeasts, bacteria, and fungi impH-cate limitations for a commerdal SCOs production process. An overview is hsted in Table 5.12. The main reasons are the costly downstream process of the SCOs and the high costs of carbon sources for heterotrophic microorganisms. 

Bio-based succinic acid is a very promising compound which can be used in many different application fields and has the potential to substitute several petroleum-based bulk chemicals. Research within the past years led to the development of a number of different production strains, fermentation strategies, and downstream processes suitable for industrial needs. Based on these results, several companies started bio-succinic acid production at industrial scale. The short overview of these companies given above, which is certainly not complete, and... 

Depending on the downstream process (H2, CO, oxosynthesis, ammonia, etc.), the product gas goes to the different unit operations as described in the section Overview. In the case of hydrogen production, this usually involves a shift reactor and a pressure-swing-absorption reactor (PSA) (Fig. 4). For CO production, the scheme involves a CO2 removal section and a low temperature separation unit (so-called cold box). CO2 is recycled to the reformer. If in this case, H2 product is also desired, a PSA unit may also be present (Fig. 5). 

The following sections will give a detailed overview on the downstream processing of the amorphous solid dispersions manufactured by different technologies. Overall, it can be concluded that the downstream process should avoid the use of water, higher temperatures and pressures as much as possible. 

Chapter 1 is used to review the history of polyethylene, to survey quintessential features and nomenclatures for this versatile polymer and to introduce transition metal catalysts (the most important catalysts for industrial polyethylene). Free radical polymerization of ethylene and organic peroxide initiators are discussed in Chapter 2. Also in Chapter 2, hazards of organic peroxides and high pressure processes are briefly addressed. Transition metal catalysts are essential to production of nearly three quarters of all polyethylene manufactured and are described in Chapters 3, 5 and 6. Metal alkyl cocatalysts used with transition metal catalysts and their potentially hazardous reactivity with air and water are reviewed in Chapter 4. Chapter 7 gives an overview of processes used in manufacture of polyethylene and contrasts the wide range of operating conditions characteristic of each process. Chapter 8 surveys downstream aspects of polyethylene (additives, rheology, environmental issues, etc.). However, topics in Chapter 8 are complex and extensive subjects unto themselves and detailed discussions are beyond the scope of an introductory text. 

PID The Piping and Instrumentation Diagram (P ID) shows in detail all the equipment, how it is connected with piping, where and what type of instrumentation and valves are used, the location of temperature, pressure, level and flow controllers (and indicators). Further it will show all the safety devices and alarms. The PI Ds give a comprehensive overview over the plant or the unit and it is a common document for mechanical, process, and instrumentation engineers in the downstream activities [851]. 

A FIGURE 12-2 Overview of mRNA processing in eukaryotes. Shortly after RNA polymerase II Initiates transcription at the first nucleotide of the first exon of a gene, the 5 end of the nascent RNA Is capped with 7-methylguanylate (step ). Transcription by RNA polymerase 11 terminates at any one of multiple termination sites downstream from the poly(A) site, which Is located at the 3 end of the final exon. After the primary transcript Is cleaved at the poly(A) site (step S),... 

This paper is meant to be an overview of the developments in the use of aqueous two-phase systems in the recovery of products of fermentation, and also purification of proteins and other biomolecules. It also touches upon the means to improve the economics of the process to make it industrially feasible. It has been realized that the closer integration of bioconversion processes with downstream technology is essential for quicker and more economical enrichment of the product. Initial efforts have already been taken in this direction, some of which are discussed here. 

FIGURE 3 Overview of hyaluronic acid biotechnological production process from Streptococcus zooepidemicus fermentation to recently proposed downstream procedure as described by Rangaswamy and Jain (2008). 

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