Downstream bioprocessing

Specific liquid chromatography methodologies and resins have been especially developed for the purpose this is a peculiar situation in the discipline of downstream bioprocessing. Today monoclonal antibodies and more largely immunoglobulins with all their derivatives represent by far the largest class of produced and purified protein in number and mass. 

Briefly compare and contrast downstream processing for bioprocesses and for purely chemical synthetic processes, from an economic perspective. 

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. 

Downstream Processing Microfiltration plays a significant role in downstream processing of fermentation products in the pharmaceutical and bioprocessing industry. Examples are clarification of fermentation broths, sterile filtration, cell recycle in continuous fermentation, harvesting mammahan cells, cell washing, mycelia recovery, lysate recovery, enzyme purification, vaccines, and so forth. 

In terms of the process, very little has been achieved. The mass transfer limitations still exist although emulsification has solved the problem partially, but not without creating another problem downstream in separation of the product from the rest of the stream and the issue still needs further work. The IP portfolio contains very few real process concepts. The patented material refers to a BDS process several times, but the process referred to, is no more than a simple description of the pH, temperature, etc., and the particular use of a given biocatalyst in an application. Some protected subject matter concerns the integration of a bioprocess into the flow sheet of the refinery, but again those are no more than theoretical scheme proposed for implementation, with no actual evidence with real feedstocks. 

Before the details of a particular reactor are specified, the biochemical engineer must develop a process strategy that suits the biokinetic requirements of the particular organisms in use and that integrates the bioreactor into the entire process. Reactor costs, raw material costs, downstream processing requirements, and the need for auxiliary equipment will all influence the final process design. A complete discussion of this topic is beyond the scope of this chapter, but a few comments on reactor choice for particular bioprocesses is appropriate. 

Jager V (1992) In Kreysa G, Driesel AJ (eds) Microbial principles in bioprocesses cell culture technology, downstream processing and recovery. DECHEMA, Frankfurt am Main, p 265... 

The third major Hmitation of bioprocesses is the quite low product concentration compared with chemical processes, resulting in high downstream processing costs. This is mainly caused by product inhibition of cell growth and biosynthesis. Physiological improvements in cell growth and product formation only have a limited impact on this aspect. Chemical or directed mutagenesis may provide better chances for improvement. Unfortunately, the molecular mechanisms of product inhibition are not well understood. 

Operation of this pilot plant demonstrated that solid/gas biocatalysis was able to compete with classical esterification bioprocesses (systems working with hexane as solvent), reducing any potential risk to a minimum by virtue of the absence of any solvent and greatly simplifying the downstream process by reducing the volumes that have to be treated by distillation to obtain a pure product. 

When planning an industrial-scale bioprocess, the main requirement is to scale up each of the process steps. As the principles of the unit operations used in these downstream processes have been outlined in previous chapters, at this point we discuss only examples of practical applications and scaling-up methods of two unit operations that are frequently used in downstream processes (i) cell separation by filtration and microfiltration and (ii) chromatography for fine purification of the target products. 

In the downstream processing of bioprocesses, fixed-bed adsorbers are used extensively both for the recovery of a target and for the removal of contaminants. Moreover, their performance can be estimated from the breakthrough curve, as stated in Chapter 11. The break time tg is given by Equation 11.13, and the extent of the adsorption capacity of the fixed bed utilized at the break point and loss of adsorbate can be calculated from the break time and the adsorption equilibrium. Affinity chromatography, as weii as some ion-exchange chromatography, are operated as specific adsorption and desorption steps, and the overall performance is affected by the column capacity available at the break point and the total operation time. 

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