Unit Operations in Downstream Processing

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. 

FIG. 20-86 General stages in downstream processing for protein production indicating representative types of unit operations used at each stage. 

It is useful to subdivide the downstream processing of recombinant proteins into a few key stages, often referred to as initial processing of the source material and extraction (if necessary), capture, intermediate purification and polishing. These can then be further split into unit operations. In each of these stages, predefined goals have to be achieved, so a well-defined purification protocol will sequentially utilize as... 

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 chemical industries, the pretreatment of educts, their chemical conversion into valuable products, and the purification of resulting product mixtures in downstream processes are carried out traditionally in sequentially structured trains of unit operations. In many cases, the performance of this classical chemical process structure can be significantly improved by an integrative coupling of different process units. 

Microfiltration is a unit operation for the separation of small particles. The separation limits are between 0.02 and 10 (jum particle dimensions. Microfiltration can be carried out in a dead-end mode and a cross-flow mode. In downstream processing, the cross-flow filtration is carried out continuously or discontinuously. The most important parameters that determine the productivity of cross-flow microfiltration are transmembrane pressure, velocity, particle size and surface, viscosity of the liquid and additives such as surfactants, and changing the surface and surface tension. 

Control analysis and control system design for chemical and petroleum processes have traditionally followed the unit operations approach" (Stephanopoulos, 1983). First, all of the control loops were established individually for each unit or piece of equipment in the plant. Then the pieces were combined together into an entire plant. This meant that any conflicts among the control loops somehow had to be reconciled. The implicit assumption of this approach was that the sum of the individual parts could effectively comprise the whole of the plant s control system. Over the last few decades, process control researchers and practitioners have developed effective control schemes for many of the traditional chemical unit operations. And for processes where these unit operations are arranged in series, each downstream unit simply sees disturbances from its upstream neighbor. 

Downstream processing of APIs using filtration and drying is often underestimated and can frequently be a bottleneck in API manufacturing processes. It is therefore vital to keep these downstream unit operations in mind when a salt form or API candidate is selected or when the crystallization process is designed. 

Jaksland et al. (1995) developed a property based approach to synthesis of chemical processes which is based on utilising driving forces to characterise the effectiveness of alternative unit operations. Each separation process exploits specific property differences to facilitate purification of the various components in a stream. The key driving force, and corresponding key property, utilised by each technology is identified. Table 1 summarizes properties of several downstream purification operations used in biochemical processes (proposed values of feasibility indices can be found in Steffens et al. 2(KX)a). The approach relies on estimates of the physical properties of the components in the system. 

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