Fine Chemical and Pharmaceutical Industry

Bioprocess plants are an essential part of food, fine chemical and pharmaceutical industries. Use of microorganisms to transform biological materials for production of fermented foods, cheese and chemicals has its antiquity. Bioprocesses have been developed for an enoimous range of commercial products, as listed in Table 1.1. Most of the products originate from relatively cheap raw materials. Production of industrial alcohols and organic solvents is mostly originated from cheap feed stocks. The more expensive and special bioprocesses are in the production of antibiotics, monoclonal antibodies and vaccines. Industrial enzymes and living cells such as baker s yeast and brewer s yeast are also commercial products obtained from bioprocess plants. 

Heterogeneous Catalysis in the Fine Chemical and Pharmaceutical Industries... 

Catalysts are extensively used and have played a huge role in making bulk chemical manufacturing technology more competitive and environmentally fnendly. Undoubtedly catalysis will continue to provide the answer to many economic and environmental challenges currently faced by industry. As indicated above catalysts are now needed by the fine chemical and pharmaceutical industries, and they need to be robust, selective, recoverable and reusable. 

Friedel-Crafts acylation is widely used for the production of aromatic ketones applied as intermediates in both fine chemicals and pharmaceutical industries. The reaction is carried out by using conventional homogenous catalysts, which represents significant technical and environmental problems. The present work reports the results obtained in the Friedel-Crafts acylation of aromatic substrates (anisole and 2-methoxynaphthalene) catalyzed by Beta zeolite obtained by crystallization of silanized seeds. This material exhibits hierarchical porosity and enhanced textural properties. For the anisole acylation, the catalytic activity over the conventional Beta zeolite is slightly higher than with the modified Beta material, probably due to the relatively small size of this substrate and the weaker acidity of the last sample. However, the opposite occurred in the acylation of a bulky substrate (2-methoxynaphthalene), with the modified Beta showing a higher conversion. This result is interpreted due to the presence of a hierarchical porosity in this material, which favors the accessibility to the active sites. 

Renken 2005 Hessel et al. 2005a, b Golb and Hessel 2004 Kockmann et al. 2006). Here, some concepts and recent developments relevant to synthetic chemists will be summarized. Microreactor technology is beginning to be used in the fine chemical and pharmaceutical industries (Hessel et al. 2005b), and several success stories have been reported already (Thayer 2005 Rouhi 2004). 

Roberge DM, Ducry L, Bieler N et al (2005) Microreactor technology a revolution for the fine chemical and pharmaceutical industries Chem Eng Technol 28(3) 318-323... 

Roberge DM, Zimmermann B, Rainone F et al (2008) Microreactor technology and continuous processes in the fine chemical and pharmaceutical industry is the revolution underway Org Process Res Dev 12(5) 905-910 www.syrris.com/. Accessed 14 Sept 2009... 

C. S. Rao, The Chemistry of Process Development in Fine Chemical and Pharmaceutical Industry, Asian Books Private Ltd., 2004, 1311 pages—ISBN 81-86299-50-5 http //www.asianbooksindia.com... 

Obviously there is a definite need in the fine chemical and pharmaceutical industry for catalytic systems that are green and scalable and have broad utihty [10]. More recently, oxidations with the inexpensive household bleach (NaOCl) catalyzed by stable nitroxyl radicals, such as TEMPO [17] and PIPO [18], have emerged as more environmentally friendly methods. It is worth noting at this juncture that greenness is a relative description and there are many shades of green. Although the use of NaOCl as the terminal oxidant affords NaCl as the by-product and may lead to the formation of chlorinated impurities, it constitutes a dramatic improvement compared to the use of chromium(VI) and other... 

These issues surrounding a wide range of volatile and nonvolatile, polar aprotic solvents have shmulated the fine chemicals and pharmaceutical industries to seek... 

An analysis based on reaction kinetics suggests that up to 50% of manufacturing reaction steps in the fine chemical and pharmaceutical industries could benefit from being run continuously rather than in batch mode in a stirred tank reactor... 

In the present chapter, we focus on the methods of risk analysis as they are performed in the chemical industry, and especially in fine chemicals and pharmaceutical industries. 

Organizational measures are based on human action for their performance. In the fine chemicals and pharmaceutical industries, reactor-charging operations are often manual operations and the product identification relies on the operator. In this context, quality systems act as support to safety, since they require a high degree of traceability and reliability. Examples of such measures are labeling, double visual checks, response to acoustic or optical alarms, in process control, and so on. The efficiency of theses measures is entirely based on the discipline and instruction of the operators. Therefore, they must be accompanied by programs of instructions, where the adequate procedures are learned in training. 

In this section, a safety dataset, resulting from over 20 years of practical experience with risk analysis of chemical processes, is presented. These data build the base of risk analysis in the fine chemicals and pharmaceutical industries, essentially in multi-purpose plants. Therefore, the dataset introduces plant considerations only at its end. This allows exchanging them without any need for recollecting the whole dataset, in cases where the process is transferred from one plant unit to another. Moreover, this dataset may be used in the frame of different risk analysis methods. 

In this section, a selection of commonly used hazard identification techniques is presented. These techniques can be used in the fine chemicals and pharmaceutical industries. The methods presented here are designed to provide a systematic search for hazards with the final objective of providing a comprehensive analysis. 

The check list method is based on past experience. The process description, the operating mode, is screened using a list of possible failures or deviations from this particular operating mode. Thus, it is obvious that the quality and comprehensiveness of the check list directly govern its efficiency. Indeed, the experience of the authors confirms that the check list is essential. This method is well adapted to discontinuous processes as practised in the fine chemicals and pharmaceutical industries, where processes are often performed in multi-purpose plants. The basic document for the hazard identification is the process description, also called operating mode. Each step of the process is analysed with the check list. 

These two factors mean the semi-batch reactor is a commonly-used reactor type in the fine chemicals and pharmaceutical industries. It retains the advantages of flexibility and versatility of the batch reactor and compensates its weaknesses in the reaction course control by the addition of, at least, one of the reactants. 

In the fine chemicals and pharmaceutical industries, reactors are often used for diverse processes. In such a case, it is difficult to define a scenario for the design of the pressure relief system. Nevertheless, this is required by law in many countries. Thus, a specific approach must be found to solve the problem. One possibility, that is applicable for tempered systems, consists of reversing the approach. Instead of dimensioning the safety valve or bursting disk, one can choose a practicable size and calculate its relief capacity for two-phase flow with commonly-used solvents. This relief capacity will impose a maximum heat release rate for the reaction at the temperature corresponding to the relief pressure. 

Quantitative failure frequency data are difficult to obtain for multipurpose batch plants in the way that they are often used in the fine chemicals and pharmaceutical industries. Moreover, a quantitative assessment requires detailed knowledge of the control instruments, which may not be available during process development Therefore, a semi-quantitative approach is proposed, providing the required reliability for future plant equipment. 

The present book is rooted in a lecture on chemical process safety at graduate level (Masters) at the Swiss Federal Institute of Technology in Lausanne. It is also based on experience gained in numerous training courses for professionals held at the Swiss Institute for the Promotion of Safety Security, as well as in a number of major chemical and pharmaceutical companies. Thus it has the character of a textbook and addresses students, but also addresses professional chemists, chemical engineers or engineers in process development and production of fine chemicals and pharmaceutical industries, as support for their practice of process safety. 

Business aspects are changing due to the expansion of the globalization of the world economy There are more potential competitors in this enlarged market. The best low-cost position is necessary to obtain and maintain market share. This is true for the fine chemical and pharmaceutical industries, because transportation costs are only a small amount of total production costs and because the total global market may in theory be supplied by producers from any place in the world. On the other hand, for the bulk chemical industry as well, small cost... 

Since mesoporous materials contain pores from 2 nm upwards, these materials are not restricted to the catalysis of small molecules only, as is the case for zeolites. Therefore, mesoporous materials have great potential in catalytic/separation technology applications in the fine chemical and pharmaceutical industries. The first mesoporous materials were pure silicates and aluminosilicates. More recently, the addition of key metallic or molecular species into or onto the siliceous mesoporous framework, and the synthesis of various other mesoporous transition metal oxide materials, has extended their applications to very diverse areas of technology. Potential uses for mesoporous smart materials in sensors, solar cells, nanoelectrodes, optical devices, batteries, fuel cells and electrochromic devices, amongst other applications, have been suggested in the literature.11 51... 

In this chapter, continuous operation has been implicitly assumed. However, batch operation is very often used in both the fine chemical and pharmaceutical industries. Analysing and designing batch equipment is generally different from the equivalent continuous units, in that... 

Figure 5.13 A schematic representation with typical process steps in the fine chemical and pharmaceutical industries and recommendation when to use microreactor technology or continuous processes based on a multipurpose approach (by courtesy of PharmaChem/B5Srl) [44].

The second set of reactions is more related to the fine chemicals and pharmaceutical industries, although some of them are carried out industrially on a very significant scale. Temperature-control in three-phase systems is easier, and is rarely a problem, but adequate mixing of the phases is essential to avoid mass-transport limitation. Selectivity here is more directed towards securing the desired product, which may be one of several closely related ones. 

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