Laboratory-scale Requirements

After development of a new process scheme at laboratory scale, constmction and operation of pilot-plant faciUties to confirm scale-up information often require two or three years. An additional two to three years is commonly required for final design, fabrication of special equipment, and constmction of the plant. Thus, projections of raw material costs and availabiUty five to ten years into the future become important in adopting any new process significantly different from the current technology. 

Eor evaluation of flocculants for pressure belt filters, both laboratory-scale filters and filter simulators are available (52,53) in many cases from the manufacturers of the full-scale equipment. The former can be mn either batchwise or continuously the simulators require less substrate and are mn batchwise. The observed parameters include cake moisture, free drainage, release of the cake from the filter cloth, filter blinding, and retention of the flocculated material during appHcation of pressure. 

Peclet number independent of Reynolds number also means that turbulent diffusion or dispersion is directly proportional to the fluid velocity. In general, reactors that are simple in construction, (tubular reactors and adiabatic reactors) approach their ideal condition much better in commercial size then on laboratory scale. On small scale and corresponding low flows, they are handicapped by significant temperature and concentration gradients that are not even well defined. In contrast, recycle reactors and CSTRs come much closer to their ideal state in laboratory sizes than in large equipment. The energy requirement for recycle reaci ors grows with the square of the volume. This limits increases in size or applicable recycle ratios. 

Four column systems are available from Amersham Pharmacia Biotech that can be used to pack SEC media for various applications at the laboratory scale. These include C, XK, SR, and HR column systems. All of the laboratory-scale columns are constructed with borosilicate glass tubes. Columns for larger scale process applications include INdEX, BPG, EineLINE, BPSS, and Stack columns. The larger scale columns are constructed to meet stringent validation requirements for the production of biopharmaceuticals. Each of the column types are described. 

Most of the byproduct HCl is used captively, primarily in oxyhydrochlorination processes for making vinyl chloride and chlorinated solvents or for Mg processing (p, 110), The scale of the industry is enormous for example, 5,2 million tonnes of HCl per annum in the US alone (1993), HCl gas for industrial use can be transmitted without difficult over moderate distances in mild-steel piping or in tank cars or trailers. It is also available in cylinders of varying size down to laboratory scale lecture bottles containing 225 g. Aqueous hydrochloric acid consumption (1993) was 1,57 Mt (100% basis). Price for anhydrous HCl is 330/tonne and for 31,4% aqueous acid 73/tonne (1993) depending on plant location and amount required. 

The control of these and any other parameters is most usually done in fermenter vessels specifically designed for the purpose and accommodating various working volumes, depending on the yield and production requirements. Laboratory-scale vessels could have a capacity of just 10 litres or less whereas clinical trials and production vessels may be as large as several thousand litres. 

Special reactors are required to conduct biochemical reactions for the transformation and production of chemical and biological substances involving the use of biocatalysts (enzymes, immobilised enzymes, microorganisms, plant and animal cells). These bioreactors have to be designed so that the enzymes or living organisms can be used under defined, optimal conditions. The bioreactors which are mainly used on laboratory scale and industrially are roller bottles, shake flasks, stirred tanks and bubble columns (see Table 1). 

A third factor affecting the quantity to be processed is the scale of the processing operation. A laboratory-scale operation will typically require less sample than a pilot-scale operation and much less than a commercial scale operation. Throughout the process, each unit operation must be supplied sufficient material to operate the process adequately while providing representative samples from the process. 

However, the transfer of this technology from laboratory to industrial scale requires advances in the engineering of biocatalysis environment, particularly when one or more components are poorly water soluble [5-8]. 

Although the asymmetric hydrogenation route to 3,3-diphenylalanine via this modified substrate preparation was not developed further, Dowpharma had a requirement to rapidly develop and scale up the manufacture of a related 3,3-diarylalanine product. The work to 3,3-diphenylalanine centred around substrate preparation and removal of impurities leading to high activity associated with the PhanePhos catalyst system allowed for a facile transfer from laboratory scale experiments to the commercial manufacture of the related diphenylalanine derivative by a robust, reproducible and scaleable procedure. 

Another advantage of the micro-LC approach is that the required sample size is minimal, so the sample can be drawn from a 1-1 laboratory scale reactor without influencing the reactor composition. The ISCO pLC-500 microflow syringe pump has proven to be reliable and reproducible in evaluations in our laboratory. Capillary liquid columns have been fabricated on planar devices such as silicon to form a miniaturized separation device.19... 

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