Monitoring, biotechnology

Mass spectrometry (MS) is one sophisticated technique that has been applied relatively recently for monitoring biotechnological processes, but mainly for the on-line detection and quantification of gases [27], MS is described in section 2.10.2. One drawback with MS is that is requires expensive equipment and is not as easy to handle as HPLC coupled to an UV-detector. Diode-array detectors (DAD) have most recently begins to be to be used for monitoring of the fermentation of wines and ethanol [28-30],... 

Gygax D, Botta L, Ehrat M, Graf P, Lefevre G, Oroszlan P, Pfister C. Immunoassays in monitoring biotechnological drugs. Ther Drug Monit 1996 18 405 09. 

In this chapter, we have described a wide variety of sensors, ranging from pH probes to biosensor-based FIA systems, that can be used to monitor biotechnological processes. At this time, however, not many of the newer instruments (especially biosensors and probes for biomass characterization) presented here are commercially available, and of those that are, only a few have achieved widespread industrial use. This situation probably exists for a number of reasons these sensors have only been developed recently (most within the last 5-10 years) and thus potential users may be unaware of their existence many of these newer probes are expensive (primarily because they are new) and finally, the bioprocess industry has yet to fully accept this new generation of sensors. In addition, many factors are known to affect the accuracy and precision of these more complex instruments, requiring experienced personnel for operation and data interpretation. 

Other workers have also demonstrated the potential role of PyMS with ANNs in quantitative biotechnology. Kang et al.106 used the combination to quantify clavulanic-acid production in a Streptomyces clavuligerus fermentation system, while a study by Lee107 indicated that the quantification of clavulanic-acid production by PyMS-ANNs could be used to quantitatively monitor the morphological differentiation process in a Streptomyces fermentation. 

Hosobuchi, M., Kurosawa, K. and Yoshikawa, H. (1993) Application of computer on monitoring and control of fermentation process microbial conversion of ML-236B sodium to pravastatin. Biotechnology and Bioengineering, 42, 815-820. 

Oldiges, M., Kunze, M., Degenring, D. et al. (2004) Stimulation, monitoring, and analysis of pathway dynamics by metabolic profiling in the aromatic amino acid pathway. Biotechnology Progress, 20, 1623-1633. 

Synthesis of PHAs in plants can not only be used directly in biotechnology for the creation of novel crop plants, but can also be a utilized as a unique novel tool in the basic studies of plant biochemistry. PHA synthesized in plants acts as a terminal carbon sink, since plants do not have enzymes, such as PHA depolymerases [68], required for degradation of the polymer. The quantity and composition of PHA can thus be used to monitor the quantity and quality of the carbon flux to different pathways. 

Doses should be selected that are reasonable multiples of the proposed therapeutic dose to be employed, especially since in many cases the amount of material available for testing may be limited and not available in Kg amounts. Preclinical rodent or primate studies should merely provide the flags to monitor during Phase I clinical trials. Reason should prevail, not only in the selection of methods and models for assessing the potential toxicity of the new agents, but also in the use of these data for extrapolation to humans. Whether U.S. industry succeeds or fails in the biotechnology arena will depend on the quick resolution of issues such as... 

T. Scheper, T. Lorenz, W. Schmidt, and K. Schugerl, On-line measurement of culture fluorescence for process monitoring and control of biotechnology processes, Ann. NY Acad. Sci. 506, 431—445... 

With biotechnology products, the entire process must be carefully overseen/monitored by the scientists who perform fhe genetic engineering operations. Interactions with third-party manufacturing operations must be frequent. 

D. Dochain and M. Perrier. Advanced Instrumentation, Data Interpretation, and Control of Biotechnological Processes, chapter Monitoring and Adaptive Control of Bioprocesses, pages 347-400. Kluwer Academic Publishers, 1998. 

This is the consequence of the traditional application of CE in the process and product monitoring of rDNA-derived biopharmaceuticals in biotechnological industries. However, related proteins, and dimer and related substances of higher molecular mass of somatropin, and aprotinin are evaluated by means of HPLC and size exclusion chromatography, respectively, by the EP. 

In many cases, biotechnology-derived products may have many components that have biological activity. The aim should be to devise controls that monitor the various components so as to retain a consistent potency and purity. For example, the USP monograph for erythromycin [9] indicates that the principal component is erythromycin A and that the percentage of erythromycin A, erythromycin B, and erythromycin C is not less than 85.0% and not more than 100.5%. Within these parameters, the relative ratios of erythromycins A, B, and C may change. This is not always the case for biotechnology-derived products, however. For example, the USP monograph for amoxicillin [10] allows for only one active component. 

Figure 4.1 Shown here are industrial biotechnology reactors used to grow cells for production of biotechnology products. Temperature, pH, and other conditions are carefully monitored and controlled. Industrial biotechnology reactors can hold thousands of liters and stand two stories high.

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