Batch process equipment utilization

Specialty plants. These plants are capable of producing small amounts of a variety of products. Such plants are common in fine chemicals, pharmaceutic s, foods, and so on. In specialty plants, the margins are usually high, so factors such as energy costs are important but not life-and-death issues. As the production amounts are relatively small, it is not economically feasible to dedicate processing equipment to the manufac ture of only one product. Instead, batch processing is utilized so that several products (perhaps hundreds) can be manufactured with the same process equipment. The key issue in such plants is to manufacture consistently each product in accordance with its specifications. 

Clearly, the time chart shown in Fig. 4.14 indicates that individual items of equipment have a poor utilization i.e., they are in use for only a small fraction of the batch cycle time. To improve the equipment utilization, overlap batches as shown in the time-event chart in Fig. 4.15. Here, more than one batch, at difierent processing stages, resides in the process at any given time. Clearly, it is not possible to recycle directly from the separators to the reactor, since the reactor is fed at a time different from that at which the separation is carried out. A storage tank is needed to hold the recycle material. This material is then used to provide part of the feed for the next batch. The final flowsheet for batch operation is shown in Fig. 4.16. Equipment utilization might be improved further by various methods which are considered in Chap. 8 when economic tradeoffs are discussed. 

In batch process optimization, one of the principal objectives is to improve equipment utilization through reduction in dead time. This requires both structural and parameter optimization, with many options available. 

Batch processes can be synthesized by first synthesizing a continuous process and then converting it to batch operation. A Gantt (time-event) diagram can be used to identify the scope for improved equipment utilization and the need for intermediate storage. 

As discussed in Sections 14.2 and 14.3, a critical difference between batch and continuous processes lies in equipment utilization. The complexity (or simplicity) of synthesis and isolation is a critical factor in determining whether a whole process is viable for switching from B2C. Given that it takes an average of eight synthetic steps to produce an API from raw materials [51], it is clear that the average API manufacturing process is probably too complex in its current form. Reduction in the number of process steps for a continuous process will, to a first approximation, reduce the plant costs pro rata. 

When the process is operating normally, no alarms should be triggered. Within the electric utility industry, this design objective is known as "darkboard. Application of darkboard is especially important in batch plants, where much of the process equipment is operated intermittently. 

The process equipment should cover a wide range of sizes, rmits, volumes, and operating conditions, e.g., speeds, for maximum flexibility in relationship to batch size and sterile dosage form requirements. Examples of pilot plant equipment utilized for the manufacture of sterile products are shown in Fig. 1. 

The inspection should cover the evaluation and assessment of the documentation, premises, equipment, utilities and materials. It should also cover verification of data and documentation such as results, batch records, compliance with SOP and information submitted on the manufacturing method, equipment and aspects including (but not limited to) validation of the manufacturing process, validation of utilities and support systems, and validation of equipment. 

The use of automated process controls and processing equipment is more likely to be utilized in an excipient plant than in a finished dosage form manufacturing plant Use of automated equipment is appropriate when adequate inspection, calibration, and maintenance procedures are utilized. Production equipment and operations will vary depending on the type of excipient being produced, the scale of production, and the type of operation (i.e., batch vs continuous). 

In addition, some scale-up works need apparatus that are operated for preparative purposes as well, along the lines of the kilo lab, but in a flexible environment not focused exclusively on batch processing as the kilo lab is. Examples of such apparatus are fluid bed crystallizers, hydroclones for the evaluation of that method of solid/liquid separation, lyophili-zation cabinets with special vial sampling capabilities, intermediate scale membrane processing assemblies, etc. An area well suited for such testing purposes is not only highly desirable, but often facilitates preparative work by processing methods not within the scope of the kilo lab. Such an area should be reasonably open for the manipulation of portable equipment, with ample walk-in hoods and tall California racks, well distributed utilities, portable measurement panels for recorders, fiowmeters and the like. 

The validation of a new BPC entails practices that parallel those utilized for the introduction of a new pharmaceutical formulation. Thus, a large part of the initial validation effort must be linked to the developmental activities that precede commercial-scale operation. The similarity is such that aspects of reaction, and purification methodologies should be as similar as possible given of course the difference in the scale of the equipment utilized in the commercial facilities. Any differences between the BPC process utilized for the formulation batches used to establish clinical efficacy and the commercial material must be closely evaluated and their impact on the BPC products chemistry, purity profile, stability, crystal morphology, and other key attributes. 

A What-If analysis can be organized in one of two ways. The first is to divide the facility into nodes, rather like a HAZOP, except that the nodes are typically bigger and more loosely defined. The second approach is to organize the analysis by major items of equipment rather like an FMEA, and then to discuss the different types of failure mode for each. These two approaches are discussed below. Guidance to do with utilities, batch processes, operating procedures, and equipment layout is also provided. 

In many pharmaceutical and fine-chemical industries, a section or whole plant can be revamped to convert a batch process into a continuous process by making use of the PI equipment described earlier. This could lead to an improved yield, quality, and a reduced footprint and utilities. A few examples are presented to illustrate the possibilities. 

Table 6.4 summarizes the types of computer systems available in approximate order of computational power. Although the purchaser of a new fluorescence spectrometer is likely to opt for the on-line personal computer, the operator of older equipment may find significant utility in either the large batch processing computer or the time-shared computer. 

Thiele (18) stressed the utility of continuous-single and twin-screw extruders compared with Banbury batch type mixers on the basis of the working volume, that is, small working mass in the extruder channels in continuous process equipment versus a large amount of blended material per cycle in batch type mixers. With a relatively smaller working volume in an extruder, there is more enhanced intimate mixing on the microscopic scale in a shorter period of residence time. 

All these types of streams have been shown in Fig. VI/3.1.5 1 A—C, respectively. As shown in Fig. VI/3.1.2-1 A, in single stream a number of units are placed in series. Therefore, the batch process moves from one unit to another serially, following programmed instructions. Parallel stream systems can be conceived as a number of isolated serial single stream system discussed previously and shown in Fig. VI/3.1.5-IB. In a multiple—pathway system shown in Fig. VI/3.1.5 1C, there is no fixed movement of batch along any fixed path it is based on the availability of a unit of the type required. There could be usage of common resources, that is, a piece of equipment or service that is used by more than one. Common discharge header for a utility such as a steam header, for example. 

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