Scale-up of Industrial Equipment

Grimwood C., 2005. Filtering centrifuges, in Solid/Liquid Separation Scale-up of Industrial Equipment , Eds. R.J. Wakeman and E.S. Tarleton, pp. 314—374, Elsevier, Oxford. 

Wakeman R.J. and Tarleton E.S. (Eds.), 2005b. Solid/Liquid Separation - Scale-up of Industrial Equipment, Elsevier Advanced Technology, Oxford. 

This Handbook has a descriptive role and is not intended to act as a textbook of filtration technology. For that function the reader is directed to Solid Liquid Separations (2005), Principles of Industrial Filtration (2005), Scale-up of Industrial Equipment (2005), Equipment Selection and Process Design (2006) (all by R.J. Wakeman and E.S. Tarleton, Elsevier Advanced Technology) or Solid-Liquid Filtration and Separation Technology (by A. Rushton, A.S. Ward and R.G. Holdich, 2000, 2nd Edn, Wiley-VCH). 

To obtain results of interest for the design and scaling-up of industrial devices, experiments were carried out at small pilot plant scale. The conditions for the equipment and system design are listed in Table 7.3. 

The clear advantage of this approach is that detailed kinetic information and accurate modeling of large-scale devices offer the possibility to design processes with high performance in standard industrial equipment. It should be noted that if microreactors can be used to provide some quantitative information, they can be used in laboratory studies to shorten time and improve knowledge for the scale-up of existing equipment. 

Scale Up of Process. The scale up of fluidized bed coating processes has received little attention in the literature. Current practices in the pharmaceutical industry are reviewed by Mehta (1988). The basic approach described by Mehta (1988) is to scale the airflow and liquid spray rates based on the cross-sectional area for gas flow. This seems reasonable except for the fact that in the scaling of the equipment, the height of the bed increases with increasing batch size. For this reason, a time scale factor is also required. 

Many of these treatments can be straightforwardly scaled-up to industrial quantities by adding steam to calcination furnace atmospheres and carrying out various forms of solution ion exchange or chemical treatment and/or acid extractions in suitable powder and granule contacting equipment. The products vary in stability and catalytic properties because the treated materials are no longer freshly crystal-... 

In the aforementioned chapter in the First Edition Reference 1,1 mentioned, There is no such thing as a standard approach to solve compactor scale-up or compactor equipment changes in the pharmaceutical production process (1). At that time of the publication, it appeared that was very much the case history of roller compaction scale-up in the pharmaceutical industry. This understanding was based on the fact that there were no pharmaceutical industrial journal articles published at the time on the subject. On the other hand, it was also true that considerations, approaches, and examples presented in that chapter were experienced by others and were not all-inclusive. 

The scale-up of a chromatographic process to industrial scale can be difficult to achieve while maintaining an acceptable throughput and yield of product. Problems may occur which are not met at the laboratory scale, for example, the flow distribution pattern through a large-diameter column, excessive pressure drop in a longer column due to compression of some matrices, and the need to maintain equipment cleanliness over an extended number of purification cycles. 

The tank cell has found an interesting and elegant application in the sugar industry [44]. A modified Grignard reactor is used for the scale-up of the indirect oxidation of galacturonic acid [45] (Scheme 1). A vessel equipped with a mechanical stirrer and cylin-drically shaped electrodes is used to produce mucic acid. The reaction conditions are given in detail in Ref. 46. 

Many solvents commonly used in academia are rarely used for scale-up in industry. A list of such solvents is shown in Table 4.2, along with the disadvantages of these solvents and alternative solvent choices. While any solvent can be used on scale, one must compare the advantages of using an undesirable solvent to the inconvenience, additional costs, and extended process times required to protect operators and equipment. All of these considerations reduce productivity and drive up processing costs on scale. 

Roller bottle reactors have been widely used in the past and can generate cell densities upto 5.4 x 10 cells/ml.However, roller bottles are difficult to scale up and cannot meet the growing demand for therapeutic recombinant proteins. Their popularity is on the decline and are largely replaced by microcarriers, and stirred-tank or airlift bioreactors in process scale-up. Initially, industrial production of EPO by CHO cells is carried out in hundreds of roller bottles in incubation rooms equipped with robots for medium changes and product harvesting. The newer production plant for second-generation EPO employs state-of-the-art bioreactors and has three times the production capacity of the old EPO plant. 

One major development will be the consequent scaling up of these methods, an area in which many industries, equipment manufacturers and organizations (e. g. the French electricity company, EDF) are now involved. 

Scale-up of low pressure extruders usually begins in the laboratory with testing on smaller equipment. After extensive experimentation with the formulation and equipment, an optimal set of parameters is defined which includes information on the material s bulk density (before and after extrusion), the extrusion rate, the power consumption during extrusion, and the product s temperature rise. An efficiency factor is then determined by ratioing the actual extrusion rate obtained on the small equipment to the calculated theoretical maximum extrusion rate. Efficiency factors are in the range of 5-35 % for axial, 15-55 % for radial, and 35-85 % for dome extruders. This efficiency factor is then applied to the theoretical extrusion rates of the industrial extruder. Many manufacturers of extruders will also include an application related experience factor for the determination of a safe but reasonable expected extrusion rate. Fig. 8.35 depicts relative levels of extrusion pressure and shear that are applied by the various low pressure extrusion equipment. 

For the pharmaceutical industry, scale-up activities often refer to the scale-up of processes in pilot plants. More important, pharmaceutical process development frequently involves fitting a process to available plant equipment rather than designing an optimal plant for the manufacture of every drug substance in the pipeline. Only for the manufacture of commercially successful drugs is a dedicated plant designed and built. 

The evolution of chemical processes and process equipment is closely related to the methods and apparatus used in the chemistry laboratory. At the early stage of evolution of chemical industries, process steps in the manufacture of a chemical mimicked the steps used in the chemistry lab in its preparation. Most of these processes were batch processes. Some of these evolved into continuous processes as the production volumes increased. Batch processes occupy the preeminent position, even today, in the pharmaceutical and fine-chemical industries. Some of the process equipment - stirred vessels, packed towers, filters, and so on - are the up-sealed versions of the apparatus used in the chemistry laboratory of yesteryear. Process intensification (PI), which represents a paradigm shift in equipment as well as in process design, takes advantage of advances in reaction engineering and transport phenomena in the design of equipment and processes (as opposed to the mere scale-up of the apparatus of the chemistry lab and mimicking the step in the laboratory preparation). 

UF is practiced in the laboratory and on a large scale industrially. The approach can differ radically. Industrially, UF always involves cros ow, with conversion per pass generally quite low. Laboratory applications often use stirred cells, which give an approach to crossflow. Scale-up of laboratory rate data is difficult unless the laboratory-scale equipment is designed carefully and the engineer is experienced. O casionally, when dilute solutions are processed in the lab, UF is run as a conventional unstirred normal flow filter. This application is similar to ordinary filtration and is not treated here. 

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