Batch operation is characterized by two key elements: (i) the physical configuration that consists of various reactors, tanks, and the network of pipelines available to transfer material between various tanks and production units, and (ii) the sequence of processing tasks. Typically, final products are produced from a number of raw materials and intermediate products through a series of processing tasks. All processing tasks are realized in batch mode of operation, with minimum and maximum batch sizes predetermined by the nature of the processes and the capacity of the reactors . There are number of process specific issues that should be considered in a typical batch processing:
• Because the duration of chemical reactions are fixed, processing times are assumed constant and predetermined irrespective of the particular batch size.
• In many practical applications, the number and size of the individual batches are not known in advance, and hence considered as decision variables. Moreover, merging and splitting of batches are allowed.
• Processing of a single batch is carried out uninterrupted.
• The proportions of input and output materials may be fixed or variable, depending on the particular process.
• Storage conditions depend on availability and capacity of appropriate storage facilities. In extreme cases, reactors themselves can be used as intermediate storage devices.
The inherent advantages of batch processes, such as flexibility to produce multiple related products in the same facility and ability to handle variations in feed stocks, product specifications and market demand pattern, make them well suited for the manufacture of low-volume, high-value products. Ultimate goals of the industry is to reduce time-to-market, lower costs, comply with regulatory requirements, minimize waste and emissions and increase return-on-investment .
The main disadvantage of batch processing is the high proportion of unproductive time (down-time) between batches, consisting of times to charge and discharge the reactor, cleaning of vessels and pipes, and restart process.
The importance of batch processes in biotech process industries has increased significantly in recent years. Batch processes are extensively used to produce specialty chemicals, biotechnology, pharmaceutical and agricultural products. The production of these high value-added chemicals, as opposed to bulk commodity chemicals, contributes to a significant and growing portion of the revenue and earnings of bioprocess industries. Considering the growing trend in industry towards products with short life cycles and products tailored to specific market needs, rapid process development has become even more significant. With the current pressures of global competition, economic efficiency often dictates whether a manufacturer can compete on a cost basis, an issue of special relevance to the pharmaceutical industry, which is additionally faced with a lengthy government approval process for its production . Environmental concerns are also another key issue faced with batch bioprocesses today.
Batch bioprocesses refer to a partially closed system in which most of the materials required are loaded onto the bioreactor aseptically and are removed at the end of the operation. Contamination of production biore-actors may lead to economic loss and is cause for alarm. Infections by phage are particularly difficult to combat because the virus particles are small enough to escape capture by the filters used to sterilize the air provided to the bioreactors. Phage attacks can be overcome by switching to resistant strains of the microorganisms. In a batch bioprocess, the only material added and removed during the course of operation is air/gas exchange, antifoam and pH controlling agents. For years, batch fermenters were loaded, inoculated, and run to completion with nothing added except air and some agent to control foam. Most modern bioprocesses incorporate adjustments to the medium to control conditions and to supply nutrients and compounds that promote biosynthesis of the desired product. It seems obvious that changes in the batch process should affect formation of the desired product (s) and that these changes can be controlled by additions of certain materials. Also of great interest is interfacing with the bioreactor system with computers to monitor and control it. Since a bioreactor consists of a complicated system of pipes, fittings, wires, and sensors, it is open to malfunctioning. With the aid of on-line monitoring and diagnosis tools, it is now possible to detect many things that can go wrong during the process.
The cultivation broth is assumed to be uniform throughout the reactor at any instant of time in a well-mixed bioreactor. However, these processes exhibit time variant dynamic behavior and are characterized by complex, nonlinear physiological phenomena that are difficult to model.
The stirred tank bioreactor is still the workhorse of bioprocess industries involving microbial cell cultures. Although there are many alternative designs, roughly 85 percent of bioreactors in the world resemble closely to the conventional design. There were already fermentation vats such as those for beer, whiskey, pickles, or sauerkraut, but the conventional design evolved in the 1940's as the pharmaceutical companies scaled up reactors for antibiotics from shake flasks and milk bottles to stirred tanks with features to discourage entry of contaminating organisms. Typical sizes for commercial production bioreactors are 60,000 to 200,000 liters, but there are a few that are considerably larger. One famous bioreactor that was known as the Merck hot dog was a cylinder laying on its side with four or five agitators mounted along the top. Its dimensions were 3.6 m diameter by 27 m long. The world's largest industrial bioreactor is still the ICI's air lift system first operated at the Billingham, U.K. plant for producing single-cell protein in 1979. The size of a bioreactor is limited by its ability to remove the heat generated by cellular metabolism. Volume goes up by a dimension cubed while area depends on a dimension squared. This means that the volume of culture fluid overwhelms the heat transfer area when the fermenter is very large. Products based on genetic engineering tend to be produced in small amounts and are suited to much smaller bioreactors. Furthermore, production cultures derived from plant, animal, or insect cells require expensive media which contain many more special nutrients than those present in media employed for synthesis of antibiotics, vitamins, and other products with bulk markets. The microorganisms that make antibiotics, in particular, are relatively easy to cultivate because their products discourage the growth of other microorganisms. Animal cell cultures, in contrast, have no self-protection and cannot compete with hardy, rapidly-growing microorganisms that find the media delectable .
Was this article helpful?