Chemical manufacturing processes batch

Exemplarily, for a typical fine chemical manufacturing process, the simplified process scheme of the aspirin production is presented in Figure 7.14. Acetylsali-cylic acid as produced by reaction of salicylic acid and acetic anhydride in a batch reactor is subjected to a cooling crystallization. The resulting suspension is transferred to a filter to remove the solvent and acetic acid formed as by-product. 

Batch process simulation is a computer modeling technique used for the design, analysis, and optimization of batch manufacturing processes. Batch process manufacturing is practiced in industries that produce low-volume, high-value products such as pharmaceuticals, fine chemicals, biochemicals, food, consumer products, etc. Most batch manufacturing facihties are multiproduct plants that produce a variety of products. 

Sometimes the term recipe is used to designate only the raw material amounts and other parameters to be used in manufacturing a batch. Although appropriate for some batch processes, this concept is far too restrictive For others. For some products, the differences from one product to the next are largely physical as opposed to chemical. For such products, the processing instruc tions are especially important. The term formula is more appropriate for the raw material amounts and other parameters, with recipe designating the formula and the processing instruc tions. 

Switching from Batch to Continuous Processing for Fine and Intermediate-Scale Chemicals Manufacture... 

Characteristic features of bulk versus fine chemicals manufacture are shown in Table 2.1. Fine chemicals manufacture often involves multi-step syntheses and is generally performed batch-wise in multi-purpose equipment. This contrasts with bulk chemicals manufacture, which generally involves continuous processing in dedicated plants. 

As mentioned earlier, a major cause of high costs in fine chemicals manufacturing is the complexity of the processes. Hence, the key to more economical processes is reduction of the number of unit operations by judicious process integration. This pertains to the successful integration of, for example, chemical and biocatalytic steps, or of reaction steps with (catalyst) separations. A recurring problem in the batch-wise production of fine chemicals is the (perceived) necessity for solvent switches from one reaction step to another or from the reaction to the product separation. Process simplification, e.g. by integration of reaction and separation steps into a single unit operation, will provide obvious economic and environmental benefits. Examples include catalytic distillation, and the use of (catalytic) membranes to facilitate separation of products from catalysts. 

Modelling can at least facilitate the determination of the most effective scale-up program. Information from three fields is needed for modelling (1) chemical kinetics, (2) mass transfer, and (3) heat transfer. The importance of information for different processes has been qualitatively evaluated (see Table 5.3-5). Obviously, sufficiently accurate information on heat transfer is needed for batch reactors, which are of great interest for fine chemicals manufacture. Kinetic studies and modelling requires much time and effort. Therefore, the kinetics often is not known. Presently, this approach is winning in the scale-up of processes for bulk chemicals. The tools developed for scale-up of processes for bulk chemicals have been proven to be very useful. Therefore, the basics of this approach will be discussed in more detail in subsequent sections. 

In fine chemicals manufacture, batch filtration prevails. This operation is the subject of R D in various steps of process development. The aim of R D on filtration is (1) to establish an effective procedure of filtration and washing providing a filter cake and/or filtrate of desired quality, and (2) to select the most appropriate filter or centrifuge for full-scale operation and determine its productivity. The productivity is defined as ... 

Distillation is a well-known process and scale-up methods have been well established. Many computer programs for the simulation of continuous distillation columns that are operated at steady state are available. In fine chemicals manufacture, this concerns separations of products in the production of bulk fine chemicals and for solvent recovery/purification. In the past decade, software for modelling of distillation columns operated at non-steady state, including batch distillation, has been developed. In the fine chemicals business, usually batch distillation is applied. 

Empirical grey models based on non-isothermal experiments and tendency modelling will be discussed in more detail below. Identification of gross kinetics from non-isothermal data started in the 1940-ties and was mainly applied to fast gas-phase catalytic reactions with large heat effects. Reactor models for such reactions are mathematically isomorphical with those for batch reactors commonly used in fine chemicals manufacture. Hopefully, this technique can be successfully applied for fine chemistry processes. Tendency modelling is a modern technique developed at the end of 1980-ties. It has been designed for processing the data from (semi)batch reactors, also those run under non-isothermal conditions. 

The fine chemicals business is characterized by a small volume of products manufactured. Therefore, batch production predominates and small-scale reactors are used. The need to implement fine chemistry processes into existing multiproduct plants often forces the choice of batch reactors. However, safety considerations may lead to the choice of continuous processing in spite of the small scale of operation. The inventory of hazardous materials must be kept low and this is achieved only in smaller continuous reactors. Thermal mnaways are less probable in continuous equipment as proven by statistics of accidents in the chemical industries. For short reaction times, continuous or semicontinuous operation is preferred. 

Medicinal products and bulk pharmaceutical chemicals are produced mainly in batch processes. Controlling these products and chemicals at the end of their manufacturing processes is not in line with the general principle of quality assurance, which is that quality should be built into the product. It is then necessary to ensure that appropriate good manufacturing practices are adhered to throughout the manufacture of both bulk pharmaceutical chemicals (active ingredients as well as excipients) and medicinal products. 

One of the major problems with batch processing is batch-to-batch conformity. Minor changes to the operation can mean slight changes in the product from batch to batch. Fine and specialty chemicals are usually manufactured in batch processes. Yet, these products often have very tight tolerances for impurities in the final product and demand batch-to-batch variation being minimized. 

Third, processing times may require special modeling in chemical industry. While in discrete manufacturing processing times for a certain lot are usually dependent on the lot size, i.e., the number of units to be produced, this is often not true in the chemical industry. Here, processing times are often constant, irrespective of whether a reactor is filled to 70% or 90% of its capacity. This is often referred to as batch production [5], On the other hand, the quality of the material produced may depend on resource utilization. Certain reactions may not even be feasible, if a minimum bound of the procured material is not exceeded. This implies additional restrictions regarding the resource utilization level on the planning situation. 

Overall, the microreactor provides greater safety for individuals and equipment and reduces the likelihood of loss of process and the consequent disruption and even loss of sales that can follow. In common with other fine chemical manufacturers, most pharmaceutical companies have programs to capture the benefits of flow microreactors as adjuncts to or even replacements for their current batch methods for scaling up production of candidate molecules to satisfy clinical and manufacturing needs. This paper attempts to demonstrate that microreactors can be deployed more widely in pharmaceutical R D than as a tool for enhanced production and that they have the potential to underpin significant paradigm shifts in both early- and late-phase R D. 

Batch microwave reactors, reactions in, 16 554-555 Batch mixers, 16 721 Batch mononitrotoluene process, 17 265 Batch multipurpose plants, for fine chemical manufacture, 11 427 Batch nitrobenzene process, 17 252 Batch-operated settling tanks, 22 59 Batch pilot plants, 19 458 Batch plants, certified, 20 703 Batch polymerization, of vinyl acetate, 25 608... 

Designing and Operating Safe Chemical Reaction Processes (HSE 2000). Published by the U.K. Health and Safety Executive and directed to small to medium-sized chemical manufacturing companies using batch and semi-batch processes. It addresses chemical reaction hazards and inherently safer processes, hazards assessment, preventive and protective measures, and management practices. 

Company C is a small custom chemical manufacturer. Contract manufacturing accounts for its entire business. CSB staff visited a small manufacturing site with several batch chemical manufacturing operations. The nature of custom chemical manufacturing translates into very frequent changes in chemicals handled and processed. 

Company E is a large chemical manufacturer with worldwide operations. CSB staff visited a mediumsized manufacturing site. Operations included storage and handling/processing of monomers, as well as extensive batch polymerization. The site uses standardized manufacturing methods and typically handles a specific set of chemicals. 

Individuals Control Charts In some chemical and biopharmaceutical manufacturing processes involving lengthy and expensive procedures, it is not feasible to form a sample of size greater than one because only one product or one batch is available each time. When the sample size used for statistical process monitoring is limited to one, individual control charts, I and MR charts, are needed. 

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