Scale-down process

OS 12] [reactor given in [84]] [P 11] In [84], the scale-down from a 250 ml batch reactor to a 10 ml batch reactor is described. The validity of applying a pseudo-second-order kinetic model for the scaled-down processing was confirmed (Figure 4.41). 

If you want to scale up or scale down process equipment using one of the parameters in Table B.2, a typical rule of thumb is the following relation... 

For purification, scale-up considerations are important even in the earliest phases of development. It is important to avoid the use of purification techniques of limited scale-up potential even for early clinical production because thorough justification of process changes and demonstration of biochemical comparability are necessary prior to product licensure. For successful scale-up, it is important to understand the critical parameters affecting the performance of each purification step at each scale. Conversely, it is important to verify that the scaled-down process is an accurate representation of the scaled-up process, so that process validation studies, such as viral clearance and column lifetime studies, can be performed at the laboratory scale. 

Premises Expression system defined Process scalability Primary definition of process No validation Refinement of operational control parameters Development of scale-down process models for validation Process out-of-limit definition Finalization of process control parameters Fixed and defined process and products Pivotal process validation and characterization studies Validated production process Well-characterized product Robust process ... 

It is desired to scale down process capacity by 25%. In a particular heat exchanger, process gas in the tubes is heated by condensing steam in the shell. By how much will the overall heat transfer coefficient for the heat exchanger change after scale-down ... 

A centrifuge on a crystallization process plant is to be scaled down for tests. If the plant centrifuge is 1.0 m diameter and rotates at 25 Hz at what speed should a 100 mm laboratory centrifuge run if it is to duplicate plant conditions ... 

Hotter and Balannec published one of the first real proposals to use SMB as a production tool for the pharmaceutical industry, and thus to scale down a process already used on a production scale [29]. The first commercially available plant (Licosep) SMB system was offered by Separex in 1991 and was exhibited for the first time in June 1991 during the Achema Exhibition. The system consisted of 24 stainless steel columns with adjustable lengths between a few centimeters up to almost 1 meter, HPLC pumps, and mulitpositional valves. To improve the robustness of the system, a rotary valve replaced two-way valves and the pumps were modified. 

Schoutens, G. EL, Guit, R. P., Zieleman, G. J., Luyben, K. C. A. M., and Kossen, N. W. F., A Comparative Study of a Fluidised Bed Reactor and a Gas Lift Loop Reactor for the IBE Process Part I. Reactor Design and Scale Down Approach, J. Chem. Tech. Biotechnol., 36 335 (1986a)... 

Industrially, the silver is recovered from either the wash water, or the bleach fix separately or from a mixture of the two using electrolysis employing a stainless steel cathode cylinder and an anode of stainless steel mesh. A typical wash solution composition contains silver (4 g L ), sodium thiosulphate (220 g L ), sodium bisulphite (22 g L ) and sodium ferric EDTA (4 g L ). At Coventry we have used a scaled down version of the industrial process employing 250 mL samples [46]. Electrolysis experiments were performed at ambient temperature with both wash and bleach fix solutions and in which the potential applied to the cathode and the speed of rotation of the cathode were varied. The sonic energy (30 W) was supplied by a 38 kHz bath. The results are given in Tab. 6.9. The table shows that the recovery of silver on sonication of the wash or bleach fix solutions is much improved especially if the electrode is rotated while ultrasound is applied. Yields with bleach fix (which contains ferric ions) are less since Fe and Ag compete for discharge (Eqs. 6.13 and 6.14). 

Centrifngal extractors have been designed for a number of industrial uses (see succeeding chapters). In some cases they have been scaled down to laboratory size bnt mainly been nsed for developing industrial multistage processes. 

Bioreactor operation and scale-up are not completely independent processes and should be assessed as different aspects of the same problem. Bioreactor operation must then consider process scale-up not only as the next step but also, as in the classic scale-down method, as a starting point. This means that bioreaction design should be done in scalable systems. A scalable system has to be inherently simple and reliable in operation and control, for easy validation and control in a production facility [56]. 

Suffice it to say that almost all operations on scale are possible if money and time are not issues of course, money rarely flows freely, and time is one of the major issues for developing drugs. Operations are almost always changed in progressing from the discovery route to scale-up. The best approach for rapid, successful scale-up is to scale down operations to the lab, and then develop processes that can be scaled up by mimicking conditions that will subsequently be encountered on scale. 

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