Process scale overview

The physicochemical and other properties of any newly identified drug must be extensively characterized prior to its entry into clinical trials. As the vast bulk of biopharmaceuticals are proteins, a summary overview of the approach taken to initial characterization of these biomolecules is presented. A prerequisite to such characterization is initial purification of the protein. Purification to homogeneity usually requires a combination of three or more high-resolution chromatographic steps (Chapter 6). The purification protocol is designed carefully, as it usually forms the basis of subsequent pilot- and process-scale purification systems. The purified product is then subjected to a battery of tests that aim to characterize it fully. Moreover, once these characteristics have been defined, they form the basis of many of the QC identity tests routinely performed on the product during its subsequent commercial manufacture. As these identity tests are discussed in detail in Chapter 7, only an abbreviated overview is presented here, in the form of Figure 4.5. 

Overview of Dosage-Form Development and Process Scale-Up.22... 

Besides its low natural concentrations, Hg is mostly anthropogenically introduced into the environment. The anthropogenic sources of Hg are numerous and worldwide. The annual emissions are estimated to be between 2700 and 6000 tons. The global cycle of Hg involves the emission of the metal from land and water surfaces into the atmosphere, its transport in the atmosphere on a global scale, possible conversion to unidentified soluble species, and return to land and water by various depositional processes [4]. In the aquatic system numerous transformations take place, which are mainly microbiological processes. An overview of the most common Hg species in the environment is given in Figure 22.1. 

The suitability of organocatalytic reactions for larger-scale production processes of chiral building blocks has also already been demonstrated in some cases. Notably, different types of bond formation have been reported, comprising several carbon-carbon bond formations as well as oxidation processes. An overview about asymmetric organocatalytic processes with an industrial impact is given in Table 1. These syntheses comprise asymmetric organocatalytic reactions which have been scaled... 

Garcia-Ochoa, R, and Gomez, E. (2009), Bioreactor scale-up and oxygen transfer rate in microbial processes An overview, Biotechnology Advances, 27(2) 153-176. 

In this chapter we will provide an overview of the application of membrane separations for chiral resolutions. As we will focus on physical separations, the use of membranes in kinetic (bio)resolutions will not be discussed. This chapter is intended to provide an impression, though not exhaustive, of the status of the development of membrane processes for chiral separations. The different options will be discussed on the basis of their applicability on a large scale. 

Since some earlier work based on anisotropic elasticity theory had not been successful in describing the observed mechanical behaviour of NiAl (for an overview see [11]), several studies have addressed dislocation processes on the atomic length scale [6, 7, 8]. Their findings are encouraging for the use of atomistic methods, since they could explain several of the experimental observations. Nevertheless, most of the quantitative data they obtained are somewhat suspicious. For example, the Peierls stresses of the (100) and (111) dislocations are rather similar [6] and far too low to explain the measured yield stresses in hard oriented crystals. 

Abstract This review provides an overview of the development of viral protease inhibitors as antiviral drugs. We concentrate on HlV-1 protease inhibitors, as these have made the most significant advances in the recent past. Thus, we discuss the biochemistry of HlV-1 protease, inhibitor development, clinical use of inhibitors, and evolution of resistance. Since many different viruses encode essential proteases, it is possible to envision the development of a potent protease inhibitor for other viruses if the processing site sequence and the catalytic mechanism are known. At this time, interest in developing inhibitors is Umited to viruses that cause chronic disease, viruses that have the potential to cause large-scale epidemics, or viruses that are sufQciently ubiquitous that treating an acute infection would be... 

Figure 14.11 Overview of the manufacturing process for the Large-scale production of plasmid DNA. Refer to the text for further details...

All types of separate wastewater treatment steps are based on one or more of the above-mentioned basic process steps. In practise a large number of treatment steps are applied, some on a large scale, others on a smaller scale.1,2 3 4 5 6 7In the following an overview is given of the most important separate treatment steps. The starting point in this overview is the type of pollutant and the physical state of the pollutant. The overview is aimed as a brief indication of separate treatment steps which are potentially applicable to remove the specific type of pollutant. More detailed information about principles, possibilities of application, removal efficiencies, bottlenecks and... 

For the quantitative description of the metabolic state of a cell, and likewise which is of particular interest within this review as input for metabolic models, experimental information about the level of metabolites is pivotal. Over the last decades, a variety of experimental methods for metabolite quantification have been developed, each with specific scopes and limits. While some methods aim at an exact quantification of single metabolites, other methods aim to capture relative levels of as many metabolites as possible. However, before providing an overview about the different methods for metabolite measurements, it is essential to recall that the time scales of metabolism are very fast Accordingly, for invasive methods samples have to be taken quickly and metabolism has to be stopped, usually by quick-freezing, for example, in liquid nitrogen. Subsequently, all further processing has to be performed in a way that prevents enzymatic reactions to proceed, either by separating enzymes and metabolites or by suspension in a nonpolar solvent. 

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