Scale-Up From Bench to Plant

A med chem route is very rarely amenable to scale-up. This statement is not a condemnation of the chemistry skills of the medicinal chemistry group. Medicinal chemists make molecules for testing and optimization. How the molecules are made is less important than the fact that they are made and made quickly. Only when a compound shows sufficient promise as a candidate is time invested to significantly improve the efficiency of its synthesis. 

Case Studies are the best method for demonstrating the degree to which a synthetic route may be modified on its way to becoming the process or commercial route. 

SCHEME 13.10 Synthesis ofacyclized, prodrug analogue of fluvastatin21 

The process route to fluvastatin reduced the number of synthetic steps from eleven to six. None of the steps 

Forming a sulfonyl chloride in the synthetic route is inevitable, so the process group sought to place the 

---

Solids, Solids, Solids 13.3 Scale-Up From Bench to Plant... 

Beltran F J, Encinar J M, Garcia-Araya J F (1995) Modelling Industrial Waste waters Ozonation in Bubble Contactors Scale-up from Bench to Pilot Plant. In Proceedings, Vol. 1 369-380, 12lh Ozone World Congress, May 15-18, 1995, International Ozone Association, Lille France. 

Beltran FJ, Encinar JM, Garcia-Araya JF. Modelling industrial wastewater ozonation in bubble contactors. 2. Scale-up from bench to pilot plant. Ozone Sci Eng 1995 17 379-398. 

Fluid bed processes have been subject to many problems and uncertainties in development and scale up from bench-scale reactors. The fluidization behavior of each process seems different and very often does not meet expectations based on experience with earlier plants. With hindsight fluid cat cracking seems to be an ideal system from the point of view of easy operation and straightforward scale up. 

Avidan and Edwards (1986) successfully scaled up from bench scale to demonstration plant from 0.04 m to 0.6 m diameter while maintaining nearly 100% conversion for a fluid bed methanol to gasoline process. In this case, they ran at a superficial gas velocity which was high enough to be in the turbulent flow regime suppressing bubbles. By this technique they eliminated the losses associated with gas bypassing in bubbles. 

As fluidized beds are scaled up from bench scale to commercial plant size the hydrodynamic behavior of the bed changes, resulting, in many cases, in a loss of performance. Although there have been some studies of the influence of bed diameter on overall performance as well as detailed behavior such as solids mixing and bubble characteristics, generalized rules to guide scale-up are not available. The influence of bed diameter on performance will differ for different flow regimes of fluidization. 

It was decided to keep these two factors as close as possible during scale-up from bench-scale studies to the pilot plant studies. The first factor controls the rate of adsorption, and the throughput controls the capacity of the XAD-4 quaternary resin. 

The MTG process is one of several processes based on ZSM-5 catalysts which are currently licensed by Mobil to the petroleum and petrochemical industry. Over 25 commercial plants have been commissioned using these catalysts. All of these applications use fixed-bed reactors and, very importantly, all were scaled-up from bench-scale pilot plant data (ref. 2). The major advantage of fixed-bed technology is that it can be relatively simple and requires minimum scale-up studies. This successful scale-up experience with ZSM-5 catalyst was an important consideration in the MTG process development for the New Zealand plant. 

The slurry polymerization process with prepolymer has been scaled up from bench-scale (100 grams) to pilot-plant operation (0.5-ton batches) without major difficulties. An important aspect of this process is the absence of reactor fouling. 

The scientific basis of extractive metallurgy is inorganic physical chemistry, mainly chemical thermodynamics and kinetics (see Thermodynamic properties). Metallurgical engineering reties on basic chemical engineering science, material and energy balances, and heat and mass transport. Metallurgical systems, however, are often complex. Scale-up from the bench to the commercial plant is more difficult than for other chemical processes. 

There are examples of successful operations that have not gone through the pilot plant stage but have been scaled up directly from bench-scale data. Thus, one process for the separation of (bulk) rare earths from an aqueous solution scaled up from only bench-scale information to contactors capable of flow rates of 500gal(UK)min (2.3m min ). As it happened, these contactors were ideal for this particular process. 

Smooth scale-ups from R D laboratory or bench scale to pilot scale and then to commercial size batch-operated, multi-purpose chemical plants are often not easy to achieve for a variety of reasons, often resulting from compromises due to the need to use existing equipment. The consequences of this lack of scalability can be a reduction in product quality and yield, increased by-product formation, longer cycle times, and, in some cases, an inability to reproduce key product properties such as color, size, or crystal structure. These consequences invariably result in an increased use of mass and energy and a production of greater waste per unit mass of product. 

Two characteristics of plastics are processability and cost. Processing is a key factor required to commercialize a product. A process must be developed to scale up economically from bench to pilot plant and eventually to a production process. Equally important is adaptation of new polymer to economical fabrication. Successful fabrication insures that laboratory properties are inherent in end product. A processability value must be included in initial objectives and product description. 

Isolation procedures for many biochemicals are based on chromatography. Practically any substance can be selected from a crude mixture and eluted at relatively high purity from a chromatographic column with the right combination of adsorbent, conditions, and eluant. For bench scale or for a small pilot plant, such chromatography has rendered alternate procedures such as electrophoresis nearly obsolete. Unfortunately, as size increases, dispersion in the column ruins resolution. To produce small amounts or up to tens of kilograms per year, chromatography is an excellent choice. When the scale-up problem is solved, these procedures should displace some of the conventional steps in the chemical process industries. 

---