Process Development and Equipment

The information to the production engineering department will summarize the results of the process development and equipment qualification from the data as described above. Some of the main items to be reported are as described above. 

Rigorous application of thermodynamics to bioprocesses may seem a daunting task in view of the astronomical complexity of the reaction mixtures, giant biological molecules, intramolecular forces, multiple driving forces, and the multitude of phases and biological, chemical, and physical processes which have to be dealt with. However, rational, efficient, and rapid process development and equipment design can only be achieved on the basis of a sound scientific foundation, as it is available nowadays, for example, for the petrochemical industries [3]. The more extensive use of thermodynamics and... 

Process transients and equipment failures may require workers to develop a new strategy to control the process. Detection, diagnosis, and fault-compensation are tasks in which workers may have little experience and the information needs may be different from those of familiar tasks. Again, methods of task and error analyses, particularly those concerned with human cognitive functions, may be useful in deciding what information should be displayed to help workers detect process transients, diagnose their causes and develop new strategies. 

Data Base Development and Equipment Chemical Process, About 250 component failure rates and 95% Pumps, valves, pipe, motors, diesels, heal 51. 

Another important aspect related to both process technology and equipment design is the need for yield management and process control techniques embedded in the tools, which will have to provide accurate and reliable means for avoiding yield losses in manufacturing and contributing to overall improvement. From this point of view, it is expected that standards in equipment and in characterization techniques will be developed or implemented if already available. 

We try to introduce process development and engineering talents into product research programs as early as possible to help insure optimum low cost processes. We know that new equipment may have to be designed or evaluated as part of the program to develop efficient, low cost production techniques. Since these initial cost estimates are theoretical they are done primarily on paper (See Figure 3). 

An important part of any plastics research and development program is the time that should be spent on evaluating and developing new processing systems and equipment. The introduction of many new polymers and the dramatic growth of the plastics... 

This research focuses on the induced-air flotation process for the removal of dispersed oil droplets. The industrial use of induccd-air flotation devices for oil wastewater separation began in IW9. Basset1 provides the process development history, equipment description, and operating experience lor an induced air unit similar to the design used in the experiments described here. Although induced-air flotation equipment is simple, the fluid mechanics of the process are not and the arrangement of the turbine, sleeve, and perforations have been determined necessarily by trail-and-crror experimentation with small-scale units. 

Validation in quality systems includes establishment of procedures on how to qualify the equipment and machinery, how to verify the design of products, how to verify the process designed, how to verify the achievement of production procedures, how to validate the process developed, and how to validate the methods for measurement and assay. Validation also requires verification of specifications or acceptance criteria of in-process parameters relating to both raw materials and intermediate (in-process product) and finished products, and verification of acceptance criteria for in-process parameters relating to operating conditions of machinery and equipment. Further, when the medical device is assembled at the user s site, validation includes establishing procedures of how to verify assembly. 

The OQ demonstrates the equipment performance for the range of processing functions at the installation site. The tests performed may be expanded to compare with those completed as part of the FAT at the vendor s facility. Additional activities, such as CIP and SIP process development and validation, are also performed after the IQ has been successfully completed. 

Tests that have been developed from knowledge of processes, systems and equipment. 

Researchers at BASF have shown that microreactors can be utilized that give access to operating conditions that cannot be realized by means of macroscopic equipment. They succeeded in improving yield and selectivity in a highly exothermal two-phase reaction in connection with the synthesis of a vitamin precursor. At Degussa company, a microreactor test facility for proprietary reactions is under construction. The major focus in this context is the implementation of microreaction devices as powerful tools for process development and, in particular, for the evaluation of new reaction pathways. 

The selection of appropriate processing plants and equipment, economics, and future developments are important considerations that are discussed in this section. 

The manufacture of sterile products is universally acknowledged to be the most difficult of all pharmaceutical production activities to execute. When these products are manufactured using aseptic processing, poorly controlled processes can expose the patient to an unacceptable level of contamination. In rare instances contaminated products can lead to microbial infection resulting from products intended to hasten the patient s recovery. The production of sterile products requires fastidious design, operation, and maintenance of facilities and equipment. It also requires attention to detail in process development and validation to ensure success. This chapter will review the salient elements of sterile manufacturing necessary to provide acceptable levels of risk regarding sterility assurance. 

Characteristic data on ash behaviour can be obtained by laboratory tests and used for planning, e.g., run conditions for tests with pilot or PDU (process development unit) equipment. 

Rapid quantification of products and substrates in a fermentation process is essential for process development and optimization. Most fermentation laboratories have access to HPLC equipment with possibilities to couple them to quite inexpensive diode-array-detectors, and this equipment could be used for quantitative monitoring of the process. Because HPLC can allow multi-component analyses, i.e., several analytes in the same sample can be determined virtually simultaneously, and since it is often necessary to monitor more than one substance at a time, this technique is an important tool for bioprocess monitoring. HPLC coupled to expensive MS does not represent standard equipment at fermentation laboratories. Even if mass spectrometers are available, DAD is often sufficient for quantification because product concentrations are relatively high, so the MS could be used for other issues. In paper II the goal was to develop and validate a method for analytical quantification of both the product and the substrate to enable the proper characterization of the kinetics of the process i.e., the determination of the values of substrate conversion and product formation. 

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