Process-scale considerations

At industrial scale, careful consideration of the materials of construction for the bioseparation equipment is vital to ensure that the product does not become contaminated, by rust, for example, and also to assure long plant life with good reliability to maximize throughput. Materials that were suitable on a laboratory or pilot scale may no longer be appropriate, where the process and mechanical demands on the equipment may be greater. For example, the plant could be located outside where there are greater extremes of temperature in summer and winter, or equipment may need to be steam sterilized in situ rather than being autoclaved. 

It is also vital that any other components such as gaskets, O-ring seals, instruments, and other parts are checked for compatibility with the products to avoid failure in service and possible product contamination or equipment downtime for repairs to be made. 

It is recommended that a careful analysis of costs is made before making the decision to automate a particular process, looking at capital and operating costs (such as man power), and to compare the process with existing plants or competitors to see if there is an industry benchmark. 

In all industrial processes, the safety of operators and staff, as well as the general public in surrounding areas, is of paramount importance. Every effort should be made during design and construction to ensure that the bioseparation plant is safe to operate with all risks identified and minimized through appropriate precautions. 

Hazardous features to be considered will include pressure relief handling of hazardous materials such as acids and alkalis protection from steam and other high-temperature fluids and electrical classification for handling solvents or protection from water ingress, high speed rotating machinery, and noise levels. 

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Walter JK, Werz W, Berthold W. Process scale considerations in evaluation studies and scale-up. Dev Biol Stand 1996 88 99-108. 

The objectives are not realized when physical modeling are applied to complex processes. However, consideration of the appropriate differential equations at steady state for the conservation of mass, momentum, and thermal energy has resulted in various dimensionless groups. These groups must be equal for both the model and the prototype for complete similarity to exist on scale-up. 

Gross-Butler equation is that the reactant is in isotopic equilibrium with the solvent. Given that the process under consideration occurs on an exceptionally short time scale, the assumption is not necessarily valid. A very thorough analysis of the isotopic possibilities was used to show that the interpretation presented here is nonetheless correct.25... 

On a larger scale, landscape development reflects those mechanisms that expose bedrock, weather it, and transport the weathering products away. Present and past tectonism, geology, climate, soils, and vegetation are all important to landscape evolution. These factors often operate in tandem to produce characteristic landforms that presumably integrate the effects of both episodic and continuous processes over considerable periods of time. 

The principal considerations involved in design of a process-scale chromatographic purification include scalability, reproducibility, safety, and validatability. Cost factors, however, must by necessity enter into all industrial decisions. Due to the high value-added nature of most biopharmaceuticals, this cost factor is driven by throughput, rather than by capital investment cost. 

During the development of a chemical process, a choice must be made regarding the type of reactor to be used on a plant scale. Some theoretical considerations and their practical impact on reactor issues are presented here. Choosing the right type of reactor can indeed improve the safety of the process. The considerations are reflected as well in the mode of operation. Reactors are characterized by type of operation (i.e., batch, semi-batch, and continuous). 

The first example involves flammability issues that are not specifically covered in this Guidelines book. However, the discussion here is highly important for safe process design considerations and represents a good example of the problems of scale-up from test data. Runaway reactions may indeed result in the production of flammable gases so an understanding of the scale-up problems is critical. 

Abstract This chapter reviews the theoretical background for continuum models of solvation, recent advances in their implementation, and illustrative examples of their use. Continuum models are the most efficient way to include condensed-phase effects into quantum mechanical calculations, and this is typically accomplished by the using self-consistent reaction field (SCRF) approach for the electrostatic component. This approach does not automatically include the non-electrostatic component of solvation, and we review various approaches for including that aspect. The performance of various models is compared for a number of applications, with emphasis on heterocyclic tautomeric equilibria because they have been the subject of the widest variety of studies. For nonequilibrium applications, e.g., dynamics and spectroscopy, one must consider the various time scales of the solvation process and the dynamical process under consideration, and the final section of the review discusses these issues. 

The model of clusters or ensembles of sites and bonds (secondary supramolecular structure), whose size and structure are determined on the scale of a process under consideration. At this level, the local values of coordination numbers of the lattices of pores and particles, that is, number of bonds per one site, morphology of clusters, etc. are important. Examples of the problems at this level are capillary condensation or, in a general case, distribution of the condensed phase, entered into the porous space with limited filling of the pore volume, intermediate stages of sintering, drying, etc. 

A complete mix reactor can also be used to simulate a larger water body when the process under consideration has a larger time scale than the mixing processes in the lake, as the next example demonstrates. 

Although some theory and history of process scale-up is presented in several chapters, the general reader is not expected to possess special knowledge of physics or engineering since any theoretical considerations are fully explained. 

This chapter deals with the design of a pilot plant facility. Although this chapter discusses many aspects of pilot plant scale-up considerations, it is not meant as a treatise on process scale-up. Many other authors in this book discuss this subject more thoroughly. All discussions on process scale-up in this chapter are presented to serve as examples of the thought process that must be considered when engaged in the design of a facility. 

A main feature of ultrafast processes under consideration takes place in the time scale shorter than picoseconds. Thus, it is necessary to employ the laser with pulse-duration 10 fsec to study these ultrafast processes. From the uncertainty principle AE At h/2 it can be seen that using this pulse-duration, numerous vibronic states can be coherently pumped (or excited) and thus the probing signal in a pump-probe experiment will contain the information of the dynamics of both population and coherence (or phase). In other words, in order to obtain the information of ultrafast dynamics it is... 

From a mathematical point of view, we can see that Equation (5.10) is in a (nonstandard) singularly perturbed form. This suggests that the integrated processes under consideration will feature a dynamic behavior with at least two distinct time scales. Drawing on the developments in Chapters 2, 3, and 4, the following section demonstrates that these systems evolve in effect over three distinct time scales and proposes a method for deriving reduced-order, non-stiff models for the dynamics in each time scale. 

The results of the analysis above indicate that the process under consideration belongs to the general category of processes with high energy recycle. The rational development of a control framework would therefore entail a time-scale... 

From pragmatic considerations, the most important step in the establishment of viable analytical separation as well as process-scale purification of polypeptides and proteins by HPLC techniques is the selection of the appropriate sorbent. The sorbent choice represents a separation variable for which the investigator can, or may be able to, introduce some rational selection criteria. Knowledge gained about the molecular features of the target polypeptide or protein come into consideration, i.e., what is the hydrodynamic radius of the polypeptide or protein what are the surface hydrophobic or charge features as deduced from the composition, amino acid sequence, or other structural data does it contain glycosylation or other posttranslational... 

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