Manufacturing plants pilot

Chemical reaction hazards must be considered in assessing whether a process can be operated safely on the manufacturing scale. Furthermore, the effect of scale-up is particularly important. A reaction, which is innocuous on the laboratory or pilot plant scale, can be disastrous in a full-scale manufacturing plant. For example, the heat release from a highly exothermic process, such as the reduction of an aromatic nitro compound, can be easily controlled in laboratory glassware. Flowever,... 

What is very important in process development is the personnel overlap when changing the scale of the process. The head of the team that is to continue the development of a process should be involved in the research on smaller scale. Also, an important member or head of the team in the smaller scale research should participate in the further step(s) of process development. Often, a parallel operation of teams is required instead of operation in series. A pilot plant, mostly composed of existing equipment items in a company, is often required as the final step in process development. A verification of procedures and models is usually not necessarily the main objective of pilot studies. The most common reason for manufacture at pilot scale is the production of kilograms of the product for market purposes and toxicity tests. A close interaction between chemists and chemical engineers is necessary at all stages of process development. 

It is important to remember that cleaning procedures should at least be in the final stages of development, as equipment and facilities in the pilot or proposed manufacturing plant are involved, and the development of the cleaning verification test methods must be complete. 

Anderson [2] presents a wide range of topics on pharmaceutical process development, including a number of different problems related to process scale-up, such as solvent and reagent selection, purification, and limitations to various operations. He notes that most reactors used for scale-up operations are selected for flexibility in running many different processes, especially for pilot plants and multiproduct manufacturing plants. 

Step 4 A pilot plant test of the process is carried out. The scale of the pilot plant is between that of the laboratory and that of a manufacturing plant. This test has several purposes to make sure that the reaction is efficient at a larger scale, to test reactor (reaction container) designs, to determine the costs of the process, to evaluate the hazards, and to gather information on environmental impact. 

Although the pilot plant must simulate the manufacturing environment in which the new product will ultimately be produced, there are many differences in operation because of the specific objectives of the two types of facilities. The pilot plant facilitates product development activities, whereas the manufacturing plant routinely fabricates products for the marketplace. The pilot plant must be flexible in operation in order to accommodate the very nature of product development, which is often at odds with the routine required in a true manufacturing facility. 

Shortcut calculations can be quite useful to the process designer or run-plant engineer they may be used to outline process requirements (stream and equipment sizes) early in a design project, to check the output of a process simulation program for reasonableness, to help analyze or troubleshoot a unit operating in the manufacturing plant or pilot plant, or to help explain performance trends and relationships between key process variables. In some applications involving dilute... 

This book has been developed primarily from my experiences at Bristol-Myers Squibb. The principles discussed are illustrated by examples from the chemical literature, patents, and my personal experience in the laboratory, pilot plants, and manufacturing plants. Many of the guidelines for implementing processes on scale (Chapter 14) were developed by the New Brunswick staff of BMS, and the thoughts there represent many collective years of experience. 

The use of variable-speed drives in pilot plant and manufacturing plant vessels is recommended for development and scale-up of crystallization processes. This capability provides the opportunity for critical experimentation at the pilot plant scale to determine the effect of impeller speed on PSD and other variables. On the manufacturing scale, the ability to change impeller speed is the most readily adjustable parameter for manipulation on scale-up. Modem variable-frequency drives provide an excellent means to vary speed over a wide range. The added cost of variable-speed capability is minimal compared to all other methods of changing mixing... 

Another key factor in successful pilot plant and manufacturing plant operation is the appropriate use of subsurface addition of antisolvents and reactive reagents for crystallization and precipitation. The primary purpose of subsurface addition is the introduction of the agent causing supersaturation in the region of intense micromixing in the vessel to avoid local excess supersaturation with the associated potential for increased nucleation. 

The scale-up factor from laboratory to plant is approximately 1,000,000 corresponding to going from g/day to tons/day. A pilot manufacturing plant will typically produce 1-50 kg/day. Then the scale-up factors will be ... 

Assurances that new and existing chemical processes are conducted safely have never been more needed. Public awareness of the effects of chemical exposure has increased since the early 1970s. Although the initial focus of the Occupational Safety and Health Act of 1970 was on safety, clearly the emphasis now is on health. People at all levels of society are concerned about exposure to chemicals and the possible short- and longterm effects of chemicals on human health. The effects of chemicals on the environment from past or present waste sites, accidental releases or spills, and fires and explosions are reported daily in the news media. Control of all chemical processes to avoid accidental discharges and/or upsets that lead to fires, explosions, and environmental release is essential in the laboratory, the pilot plant, and the manufacturing plant. Chemical process hazard reviews are necessary at each step in the development of a process to ensure that the process can be controlled and conducted so as to minimize the risks to personnel, property, and the environment. 

The plant at Nancekuke on the beautiful Cornish coast manufactured 15 tons of GB, all of which was supposedly used for research there and at Porton. The factory had been designed as a pilot plant , as Sutton Oak had been a pilot plant for the manufacture of mustard gas. In the event, the British, unlike their American allies, never developed a full scale nerve gas manufacturing plant, a decision often represented as one akin to unilateral disarmament. In truth there was no need to expand facilities because the British had proved to their satisfaction that the system worked. In times of crisis it would be necessary only to use the experience of Nancekuke to build a larger plant to produce the nerve gas necessary for future weapons. 

Fig. 9.13 Manufacturer s pilot plant with a roller press for high-pressure agglomeration of dry particulate solids...

Fig. 9.13 Manufacturer s pilot plant with a roller press for high-pressure agglomeration of dry particulate solids Fig. 9.14 Temporarily assembled system for the testing of iron ore processing, pelletizing, firing (sintering), and cooling in a specialized vendor s fadlity Fig. 9.15 Test fadlily of a tablettmg machine manufacturer Fig. 9.16 Testing fadlily of a coating equipment manufacturer...

Excipient manufacturing plants often produce laboratory or pilot batches. Scale-up to commercial production may involve several stages and data should be reviewed to demonstrate the adequacy of the scale-up process. Scale-up may introduce significant problems in consistency among batches. Pilot batches should serve as the basis for establishing in-process and finished product purity specifications. 

Podbielniak Inc., of Chicago, manufacture automatic pilot distillation plants ( Fractioneer series. Fig. 146) in four types, suitable for batch or continuous operation in the following ranges ... 

Bulk and solution polymerization pilot plants are designed to mimic the manufacturing plants to facilitate accurate scale-up to the manufacturing process. Often in the liter to tens of liters sizes, they are usually built with the same quality and safety standards of a manufacturing process with Class 1, Div. 1 or Class 1 Div. 2 rated areas. The number and sizes of the pilot reactors is a function of the development activity load and the sample sizes needed for application testing. 

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