Process-scale level

Consequently, these models often require model tuning through semiempirical correlations and data integration. Such tasks are time-consuming and problem specific as they often require information from additional experiments and pilot plant trials, with missing information leading to start-up and operational risks. The incorporation of more accurate multi-scale phenomena (at device-, meso- and even molecular scales) captured by reduced-order models (ROMs) will overcome these limitations (Lang et al., 2009, 2011). 

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Another important class of titanates that can be produced by hydrothermal synthesis processes are those in the lead zirconate—lead titanate (PZT) family. These piezoelectric materials are widely used in manufacture of ultrasonic transducers, sensors, and minia ture actuators. The electrical properties of these materials are derived from the formation of a homogeneous soHd solution of the oxide end members. The process consists of preparing a coprecipitated titanium—zirconium hydroxide gel. The gel reacts with lead oxide in water to form crystalline PZT particles having an average size of about 1 ]lni (Eig. 3b). A process has been developed at BatteUe (Columbus, Ohio) to the pilot-scale level (5-kg/h). 

At the micro-scale level, there really is no way to measure concentration fluc tuations. Resort must be made to other qualitative interpretation of results for either a process or a chemical reac tion studv. 

Shaker tube reactors are commonly used for the evaluation of catalysts at elevated pressure. The liquid reactant and powdered catalyst are introduced into a metal or glass ampoule, which is sealed and pressurized to a predetermined level with the gaseous reactant. The ampoule is immersed into a thermostatted liquid and maintained at this temperature for a certain period of time while shaking. Then the reactor is opened and the reaction mixture analysed. Ampoules of ca. 10-100 cm are typically used. The usefulness of data obtained using such reactors for process scale-up is nearly zero due to poor agitation and unknown hydrodynamics in the ampoule. These reactors are, however, very useful for fast screening of catalysts. 

Various works has pointed out the role of the nanostructure of the catalysts in their design.18-26 There is a general agreement that the nanostructure of the oxide particles is a key to control the reactivity and selectivity. Several papers have discussed the features and properties of nanostructured catalysts and oxides,27-41 but often the concept of nanostructure is not clearly defined. A heterogeneous catalyst should be optimized on a multiscale level, e.g. from the molecular level to the nano, micro- and meso-scale level.42 Therefore, not only the active site itself (molecular level) is relevant, but also the environment around the active site which orients or assist the coordination of the reactants, may induce sterical constrains on the transition state, and affect the short-range transport effects (nano-scale level).42 The catalytic surface process is in series with the transport of the reactants and the back-diffusion of the products which should be concerted with the catalytic transformation. Heat... 

The cleaning of process-scale chromatography systems used in the purification of biopharmaceuticals can also present challenges. Although such systems are disassembled periodically, this is not routinely undertaken after each production run. CIP protocols must thus be applied periodically to such systems. The level and frequency of CIP undertaken will depend largely on the level and type of contaminants present in the product-stream applied. Columns used during the earlier stages of purification may require more frequent attention than systems used as a final clean-up step of a nearly pure protein product. While each column is flushed with bulfer after each production run, a full-scale CIP procedure may be required only after every 3-10 column runs. Most of the contaminants present in such columns are acquired from these previous production runs. 

A key aspect of metal oxides is that they possess multiple functional properties acid-base, electron transfer and transport, chemisorption by a and 7i-bonding of hydrocarbons, O-insertion and H-abstraction, etc. This multi-functionality allows them to catalyze complex selective multistep transformations of hydrocarbons, as well as other catalytic reactions (NO,c conversion, for example). The control of the catalyst multi-functionality requires the ability to control not only the nanostructure, e.g. the nano-scale environment around the active site, " but also the nano-architecture, e.g. the 3D spatial organization of nano-entities. The active site is not the only relevant aspect for catalysis. The local area around the active site orients or assists the coordination of the reactants, and may induce sterical constrains on the transition state, and influences short-range transport (nano-scale level). Therefore, it plays a critical role in determining the reactivity and selectivity in multiple pathways of transformation. In addition, there are indications pointing out that the dynamics of adsorbed species, e.g. their mobility during the catalytic processes which is also an important factor determining the catalytic performances in complex surface reaction, " is influenced by the nanoarchitecture. 

Although HGMS has been used commercially on a large scale for more than 2 decades for some applications, it has been tested only at the bench-scale level for remediation of radioactive-contaminated soils and process streams. This technology is not currently commercially available for radioactive solid or liquid decontamination. 

Development of PAT approaches for process scale-up is likely to take place at several levels. At the conceptually simplest level, PAT presupposes the development of sensing instruments capable of monitoring process attributes online and in real time. 

Typically, for batch processes such as blending or drying, this entails the determination of process end-point attributes. The PAT method then becomes the centerpiece of the scale-up effort. Process scale-up can be undertaken under the assumption that the relationships between observables and performance are independent of scale, and if this assumption is verified in practice, the manufacturing process in full scale can be monitored (typically, to completion) providing a higher level of assurance that the product is likely to be within compliance. 

Agitation levels 1 and 2 are characteristic of applications requiring minimal solids-suspension levels to achieve the process result. Agitators capable of scale levels of 1 will Produce motion of all of the solids of the design settling velocity in the vessel Permit moving fillets of solids on the tank bottom, which are periodically suspended. 

Agitation levels 3 and 5 characterize most chemical process industries solids-suspension applications and are typically used for dissolving solids. Agitators capable of scale levels of 3 will Suspend all the solids of design settling velocity completely off the vessel bottom Provide slurry uniformity to at least 1 /3 of fluid-batch height Be suitable for slurry draw-off at low exit-nozzle elevations. 

Tables 2 and 3 show an antibody purification process scale-up from laboratory scale (1 mL) to intermediate scale (500 mL) to large scale of 10-85 L column volumes, maintaining the column bed height constant. Product quality and biocontaminant levels were maintained throughout the scale-up, though operational flow rates were significantly changed, demonstrating the consistency of the overall purification process. Thorough analysis of each coliunn performance is essential in order to sustain the process robustness at different scales of operation.

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