Process monitoring and control

A reliable control of the product temperature throughout the process is of the utmost importance, especially during the primary drying stage. In practice, such control can only be exercised through changes in the shelf 

In some commercial equipment, a conductimetric method is employed to measure the so-called eutectic temperature. In practice, where supersaturated solutions are the rule, eutectic temperatures are rare, and where they do occur, they are unrelated to the physical state of the drug substance. Such measurements are of little value other than indicating a change in conductance with temperature. In this role, they might give a warning of abnormal conditions. 

Apart from the product and shelf temperatures, the condenser temperature should also be monitored. This would normally be set to its lowest achievable value. A rise in the condenser temperature at some stage during the drying process is a danger sign that the condenser is unable to cope with the mass transfer rate of water vapour. 

The PRT is a popular method of determining the completion of ice sublimation. The main chamber is isolated from pump and condenser, and the rate of pressure increase is measured. In its simplest form, which suffices for most purposes, sublimation is deemed to be complete when the PRT value is equivalent to the background leak rate of the equipment, typically 1.5-3.0 Pa/min. 

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Sensors. One growth area for electronic ceramics is in sensor appHcations. Sensors (qv) are devices that transform nonelectrical inputs into electrical outputs, thus providing environmental feedback. Smart, or intelligent, sensors also allow for mechanisms such as self-diagnosis, recovery, and adjustment for process monitoring and control (see Process control). 

The second area, the implementation of a modem process monitoring and control system, is the most dramatic current appHcation of CAD/CAM technology to the chemical process industry. The state of the art is the use of computer graphics to display the process flow diagram for sections of the process, current operating conditions, and controUer-set points. The process operator can interact directly with the control algorithms through the... 

The process monitors and controllers typically also have the capabiUty for data logging, analysis, and display. This capabiUty has made on-line control of pilot plants, as well as commercial-scale processes, desirable. Pilot-plant appHcations for on-line control have been described (106), and the use of such systems for both monitoring and process diagnosis has been discussed (107). A number of commercially available process control programs that mn on microprocessors have been reviewed (108). Virtually all of them incorporate graphic display as an integral part of the interactive capabiUty of the program. 

The creation and analysis of process flow sheets has become much easier because of the availabihty of automated systems to draw and revise them. The goal of the use of the flow sheet as the input for process simulation and for process control is likely to be achieved reasonably soon. The use of interactive graphic displays for process monitoring and control is pervasive today. 

A number of composition analyzers used for process monitoring and control require chemical conversion of one or more sample components preceding quantitative measurement. These reactions include... 

The purpose of the control plan is to ensure that all process outputs will be in a state of control by providing process monitoring and control methods to control product and process characteristics. The control plan is covered in section 6 of the APQP manual. It consists of forms containing data for identifying process characteristics and helps to identify sources of variation in the inputs that cause product characteristics to vary. The APQP manual provides excellent guidance on the compilation and use of the control plan so no further guidance is given here. 

Analytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances. 

Piovoso, M. J., and Kosanovich, K. A., Applications of multivariate statistical methods to process monitoring and controller design, Int. J. Control 59(3), 743-765 (1994). 

T. Scheper, T. Lorenz, W. Schmidt, and K. Schugerl, On-line measurement of culture fluorescence for process monitoring and control of biotechnology processes, Ann. NY Acad. Sci. 506, 431—445... 

Finally, process analytics methods can be used in commercial manufacturing, either as temporary methods for gaining process information or troubleshooting, or as permanent installations for process monitoring and control. The scope of these applications is often more narrowly defined than those in development scenarios. It will be most relevant for manufacturing operations to maintain process robustness and/or reduce variability. Whereas the scientific scope is typically much more limited in permanent installations in production, the practical implementation aspects are typically much more complex than in an R D environment. The elements of safety, convenience, reliability, validation and maintenance are of equal importance for the success of the application in a permanent installation. Some typical attributes of process analytics applications and how they are applied differently in R D and manufacturing are listed in Table 2.1. 

In response to the often heard misconception that sampling is but a statistical and practical issue, the following contextualization is highly relevant for process monitoring and control. Statistical considerations... 

As will become obvious in this chapter, UV-vis spectroscopy is a valuable tool for process analytics in a wide range of industrial applications, be it in production-related R D or in actual process monitoring and control. An overview of reviews for the various fields is given in Table 4.1. 

Process monitoring and control of API production, sans the regulatory environment, is analogous to that within the chemical industry. Since the early 1990s, numerous papers have been published noting on-line specnoscopic techniques as applied to API reaction monitoring. A representation of some of these on-line specnoscopic reaction monitoring techniques will be provided herein with additional information discussed in Chapter 15. 

Wang et al. [42,67,68] have developed innovative biological process and sequencing batch reactors (SBR) specifically for removal of volatile organic compounds (VOCs) and surfactants. Related analytical procedures [57-64,71-91] available for process monitoring and control are available in the literature. 

The quality of design (product and its manufacturing process)—the ability to reliably predict quality and performance, process monitoring and controls, process capability and appropriate risk-mitigation strategies—provides an opportunity to achieve real time quality assurance (the ultimate level of efficiency). This also provides an excellent opportunity to develop efficient and effective quality assurance systems as an alternative to market or public standards (18). 

The development of sensors for industrial process monitoring and control is an area of increasing importance. In particular, there are relatively few sensors that are capable of monitoring the state of a catalyst despite the fact that catalyst state can have a very significant impact on overall process performance. Consequently, there is a need to develop new sensors for the in-situ monitoring of catalyst state. Solid electrolyte electrochemical cells show promise as sensors which could be used for intermediate and high temperature application (temperatures greater than about 200°C). 

Establishing product conformance to specified requirements by use of process monitoring and control methods... 

Hold the product until the required inspection and tests have been completed or necessary reports have been received and verified, except when the product is released under positive recall procedures (see 4.10.1). Release under positive recall procedures does not preclude the inspection, testing, and identification of the product as required by the quality plan or documented procedures. Product conformance is established to specified requirements by use of process monitoring and control methods. 

KDC, 1993. Us MDA-1000 Microwave Dielectric Analyze for Process Monitoring and Control. KDC Technology Corp., 2011 Research Dr., Livermore, CA. 

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