Scalability

Scalability is a term that is used to describe the ease and capacity for changing a process to accommodate different production volumes. To scale chemical processes 

Metrics for scalability require a specification of the critical quality attributes and a good understanding of the chemistry and the associated processes. One can then probe the limits of acceptability of these critical attributes, and by so doing will discover the scalability limits of the process. As a process is scaled up, one needs to ensure that it is operationally simple and that there are no unacceptable environmental, safety, and health risks. 

For batch chemical operations, real-time process control and understanding are rarely achieved despite recent attempts to achieve greater statistical process control. The batch chemical industry is typically able to operate at no more than about three or occasionally four sigma, or one defect in 1000-10,000. 

The green downside to three or four sigma processes is that they will produce more waste, and in the process consume more materials and energy per unit of finished product while reducing throughput and cycle time. When processes are out of control, product specifications will not be met and there is likely to be a need to reprocess the off-specification product or, in the worse-case scenario, to discard it. In either case, an out-of-control process is a problem. 

Controllability metrics might be something as simple as recording the number of excursions from statistical process control, but process capability indices are probably 

A parallel algorithm is said to be scalable if its parallel efficiency can be maintained as the number of processes increases. Scalability may be classified as either weak or strong, depending on how the efficiency varies with the number of processes and the problem size. An algorithm is weakly scalable if the efficiency does not decrease as the number of processes grows, provided that the problem size increases as well. Thus, for process counts pi and p2 and problem sizes i and 2/ with p2 pi and fi2 fiu weak scalability implies that 

A more detailed analysis of the scalability of an algorithm that can reveal the rate at which the problem size must grow to maintain a constant efficiency requires an explicit functional form for E (p, n). We will show an example of the derivation of an efficiency function in section 5.3.2. Additionally, it is important to clearly define the problem size. In computational complexity theory, the problem size is usually defined to be a measure for the size of the input required for an algorithm. For example, the problem size for a matrix-matrix multiplication involving matrices of dimensions m x m would be m. This definition for the problem size is also consistent with the one usually employed in computational chemistry, where the problem size is defined as the size of the molecule being studied, expressed, for example, in terms of the number of atoms, electrons, or basis functions. 

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. 

To measure the scalability of a process it is necessary to understand the chemistry and reaction kinetics involved and then to determine their impact on well-defined critical quality attributes desired of the product in order to find the optimum processing window within which there is certainty that the product will be of acceptable quality. However, these data are not readily available for many pharmaceutical chemistry reactions, so a subjective measure of a the scalability, robustness, and greenness of many processes has been developed by Pfizer based on operator knowledge and experience to assist development teams both in the laboratory and in pilot plants to develop greener processes [28]. 

---

J. F. Leathrum, Jr. Scalable implementations of multipole-accelerated algorithms for molecular dynamics. In Proceedings of the Scalable High-Performance Computing Conference, pages 87-94, Los Alamitos, Calif., 1994. IEEE Computer Society Press. 

Our multipole code D-PMTA, the Distributed Parallel Multipole Tree Algorithm, is a message passing code which runs both on workstation clusters and on tightly coupled machines such as the Cray T3D/T3E [11]. Figure 3 shows the parallel performance of D-PMTA on a moderately large simulation on the Cray T3E the scalability is not affected by adding the macroscopic option. 

J. A. Board, Jr. et al.. Scalable variants of Multipole-Accelerated Algorithms for Molecular Dynamics Applications, Proceedings, Seventh SIAM Conference on Parallel Processing for Scientific Computing, SIAM, Philadelphia (1995), pp. 295-300. 

Clark, T., Hanxleden, R., McCammon, J., Scott, L. Parallelizing molecular dynamics using spatial decomposition. In Proceedings of the scalable high performance computing conference. May 23-25, 1994, Knoxville, Tennessee. IEEE Computer Society Press, Los Alamitos, California, 1994. 

Some of the stand-alone programs mentioned above have an integrated modular 3D visualization application (e.g., ChemWindow —> SymApps, ChemSketch —> ACD/3D Viewer, ChemDraw —> Chem3D). These relatively simple viewers mostly generate the 3D geometries by force-field calculations. The basic visualization and manipulation features are also provided. Therefore, the molecular models can be visualized in various display styles, colors, shades, etc. and are scalable, movable and rotatable on the screen. 

Lastly, Strike asked what he thought about the scalability of this process. Can it be upped to 1 mol or more He said he was up to SOmmol and said no decrease in yield was apparent. The time of irradiation also did not need to be any longer than the written protocols. 

In order to reduce the tendency of the film to shrink oriented film may be annealed at about 100°C whilst under tension immediately after drawing. The film is often coated with another polymer sueh as a vinylidene ehloride-based copolymer. This both improves the barrier properties and improves the heat scalability. 

Because of the excellent gas barrier properties, EVOH is of interest as a packaging material. However, because of its high water absorption it is usually used as an internal layer in a co-extruded film, sheet, bottle or tube. For example, the system HDPE-EVOH-EVA may be used as a barrier film for packaging cereals, and the system polystyrene-EVOH-polystyrene for packaging coffee and cream, whilst the system polystyrene-EVOH-polyethylene has the additional advantage of heat scalability. 

Catalytic kinetic resolution can be the method of choice for the preparation of enantioenriched materials, particularly when the racemate is inexpensive and readily available and direct asymmetric routes to the optically active compounds are lacking. However, several other criteria-induding catalyst selectivity, efficiency, and cost, stoichiometric reagent cost, waste generation, volumetric throughput, ease of product isolation, scalability, and the existence of viable alternatives from the chiral pool (or classical resolution)-must be taken into consideration as well... 

Practical considerations limit, the scalability of this reaction due to the highly reactive and water sensitive intermediates formed. Furthermore, the time required for removal of large amounts of solvent in vacuo allows for the opening of the intermediate epoxide leading to diol formation. 

The primary lesson from this example is that no process is infinitely scalable. Sooner or later, additional scaleup becomes impossible, and further increases in production cannot be single-train but must add units in parallel. Fortunately for the economics of the chemical industry, the limit is seldom reached. 

Use Scalable Heat Transfer. The feed flow rate scales as S and a cold feed stream removes heat from the reaction in direct proportion to the flow rate. If the energy needed to heat the feed from to Tout can absorb the reaction exotherm, the heat balance for the reactor can be scaled indefinitely. Cooling costs may be an issue, but there are large-volume industrial processes that have Tin —40°C and Tout 200°C. Obviously, cold feed to a PFR will not work since the reaction will not start at low temperatures. Injection of cold reactants at intermediate points along the reactor is a possibility. In the limiting case of many injections, this will degrade reactor performance toward that of a CSTR. See Section 3.3 on transpired-wall reactors. 

Scale down the model to design a pilot plant that is scalable upward and that will address the most significant uncertainties in the model of the full-scale facility. 

The box is the scalable entity, which is assigned to a defined rectangular area on the printer, see (SetUp Print Job). 

One final note While the techniques used here were applied to control temperature In large, semi-batch polymerization reactors, they are by no means limited to such processes. The Ideas employed here --designing pilot plant control trials to be scalable, calculating transfer functions by time series analysis, and determining the stochastic control algorithm appropriate to the process -- can be applied In a variety of chemical and polymerization process applications. 

Smaller companies tend to have fewer concerns around, for example, system scalability, global WAN performance, and complex systems integration. They are rather more driven by the pure functionality of the ELN that is addressing the specific scientific disciplines of interest. Key drivers in this sector of the market have been medicinal chemistry departments, where the obvious benefits of searching existing reactions by substructure and reaction transformations, the ability to automate stoichiometry calculations, the ability to load spectral information, etc. have made for easy adoption and clear and realizable benefits. 

The consequence of moving consciously toward this model will be the provision of a robust and scalable IT infrastructure and systems able to cope with exponentially growing data mountains that will need to be integrated and shared, accessed and mined in the most effective way. It will also require formidable computing power and sophisticated algorithms to be able to simulate both organs and whole body systems to reduce expensive failures in the clinic and predict much earlier the pharmacokinetic and pharmacodynamic properties and toxicological and efficacy profiles of molecules in pharmaceu-... 

Rinard dedicated his research to a detailed analysis of methodological aspects of a micro-reactor plant concept which he also termed mini-plant production [85] (see also [4, 9, 10] for a commented, short description). Important criteria in this concept are JIT (Just-in-time) production, zero holdup, inherent safety, modularity and the KISS (keep it simple, stupid) principle. Based on this conceptual definition, Rinard describes different phases in plant development. Essential for his entire work is the pragmatic way of finding process solutions, truly of hybrid character ]149] (miniaturization only where really needed). Recent investigations are concerned with the scalability of hybrid micro-reactor plants and the limits thereof ]149], Expliddy he recommends jointly using micro- and meso-scale components. 

P., Campbell, T. J., Ogata, S., Shimojo, F., Saini, S., Scalable atomistic simulation algorithms for materials research,... 

Inherent hazard (e.g., toxicity, stability, reactivity) Cost Renewability Recyclability Size (volume) Scalability Controllability Energy (i.e., total, heating, cooling, recovery, treatment, etc.) Ease of cleaning and maintenance Safety/process safety ... 

To measure the scalability of a process, one needs to define the critical quality attributes and to understand the chemistry and processes involved in order to find the limits of acceptability of these critical attributes, and thus, the limits of the scalability of a process. For a chemical process to be functional at large scale it should also be operationally simple, safe and straightforward. 

Among these one of the most promising concepts is the development of single electron (SE) devices, which retain their scalability down to the molecular level. At present, due to exploitation of charging (Coulomb) effects in metallic SE devices comprising tunnel junctions with submicrometer size, individual charge carriers can be handled... 

---