Scaling-up process

The highly branched GaM of Mimosa seeds, isolated by a scaled-up process [186] at a yield of 20% of seed weight, showed a Man Gal ratio of 1.1 1 and structural features of the gum obtained on a laboratory scale [ 183]. Based on C-NMR spectroscopy of GaM from Cassia angustifolia [179], with a Man Gal ratio of 2.9 1, a blockwise pattern of the galactosyl branches was suggested. 

A plasma process that has been demonstrated to yield good quality materials in the laboratory will one day need to be scaled up to a technology that can produce the materials in larger sizes and larger quantities. Such a transfer is not straightforward, and many technological difficulties will have to be overcome before a scaled-up process is commercially viable. 

Commercialization is scale-up, process development, and marketing either as a material or as an integral part of a product. 

ChemOvation Ltd., founded in 1998, focuses on providing an integrated drug discovery support service via collaborative programs, and the manufacture of innovative compound libraries. Apart from that, their range of services includes chemistry development, automated parallel synthesis, scale-up, process development, and screening. 

Test runs using a 150 mm diameter fluid bed coater indicated that a batch of 2 kg of material could be coated using a liquid spray rate of 10 ml/min for 50 minutes and a fluidizing gas rate of 40 scfm. It is desired to scale-up this process to a batch size of 200 kg of bed material. For the scaled up process, determine the bed size the liquid and airflow rates and the new run time. 

Clearly, computer simulations can be a very useful tool to aid this design and scale-up process. Basically, such simulations can be used for two different... 

The book is directed to those persons involved in research, process development, pilot plant scale-up, process design, and commercial plant operations. It is important for technical people considering alternative process routes to know the potential hazards from the main reactions and from the unwanted side reactions in each case so that the hazards of reactivity are included in the factors reviewed in developing and selecting the final process route. 

One primary goal is to conserve selectivity throughout scale-up. This means attempting to use the same separation chemistry in development that will eventually be used in production. This avoids the need to re-optimize in each stage of the scale-up process. It is desirable to use the same support matrix to avoid unforeseen matrix effects causing uimecessary modification of developed procedures. 

Yabannavar et al. [81] proposed a proportionality relationship valid for spin-filters based on an analogy to Eq. (15). They defined the Reynolds number based on the tangential velocity at the screen surface. Since in spin-filters the permeation velocity, or perfusion flux, is given by Eq. (16), and it can be assumed that the screen porosity e will be maintained constant throughout the scale-up process, it is possible to write a proportionaHty relationship for the ratio from drag to lift force in spin-filters as given by Eq. (17). 

Dale WJ. The scale-up process optimize the use of your pilot plant. Abstract 108c, Session 108 on Experimental Strategies for Pilot Plants, 1996 Spring Meeting, Am. Inst. Chem. Engrs., New York. 

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. 

Still, we can offer some simple guidelines that can help the practitioner wade through the scale-up process ... 

The following roller compaction scale-up examples illustrate technology strategies that identify equipment design features, process parameters, and evaluations defining roller compaction scale-up processes. 

To fluidize and thus granulate and dry the product, a certain quantity of process air is required. The volume of the air required will vary, based upon the amount of material that needs to be processed. The ratio of drying capacity of the process air and quantity of the product needs to be maintained constant throughout the scaling-up process. However, some suppliers of the equipment provide higher drying capacity for their laboratory unit... 

Table 5 Scale-Up Process Parameters from 15 kg to 150 kg Batch...

In many companies, the scale-up process may include or overlap with the validation process. In any case, demonstration of the process in the production environment at full scale, using the materials, equipment, procedures, and personnel established in production, is required. Often, multidisciplinary teams are arranged to manage the scale-up, and the overall roles and responsibilities for those involved with the product may change. Typically, extensive documentation, including protocols and reports, is involved, as... 

The additional challenge to the tableting scale-up process will be to remain within these standardized ranges. 

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