Internal process control

For some applications or for quality assurance, it can be necessary to control whether instruments, surfaces, reaction tubes, or used buffers are contaminated with DNA, RNA, DNAse, or RNAse. For the detection of DNAse or RNAse, known amounts of DNA or RNA are incubated with the suspected buffers or in the tubes at 37 to 40°C for 30 to 60 min. After this, real-time PCR is performed with the untreated DNA or RNA as control. If the analysis of incubated DNA or RNA shows a higher value than the control, and the internal process control gives no hint of inhibition, DNAse or RNAse was present. For the detection of DNA or RNA contaminations, humid swab samples (in TE or phosphate-buffered saline buffer) have to be collected from surfaces or instruments and the nucleic acids extracted into the TE buffer. The buffer can also be incubated in the suspected reaction tube or pipette tip. Real-time PCR is performed with universal primers specific for cytochrome b, human DNA, or any other DNA/RNA that is identified as a source of contamination in the laboratory. 

In order to operate a process facility in a safe and efficient manner, it is essential to be able to control the process at a desired state or sequence of states. This goal is usually achieved by implementing control strategies on a broad array of hardware and software. The state of a process is characterized by specific values for a relevant set of variables, eg, temperatures, flows, pressures, compositions, etc. Both external and internal conditions, classified as uncontrollable or controllable, affect the state. Controllable conditions may be further classified as controlled, manipulated, or not controlled. Excellent overviews of the basic concepts of process control are available (1 6). 

C. L. Smith, Digital Computer Process Control, International Textbook Co., Scranton, Pa., 1964. 

George W. Gassman, B.S.M.E., Senior Research Specialist, Final Control Systems, Fisher Controls International, Inc., Marshalltown, Iowa (Section 8, Process Control)... 

The process controller is the master of the process-control system. It accepts a set point and other inputs and generates an output or outputs that it computes from a rule or set of rules that are part of its internal configuration. The controller output seiwes as an input to another controller or, more often, as an input to a final control element. The final control element is the device that affects the flow in the piping system of the process. The final control element seiwes as an interface between the process controller and the process. Control valves and adjustable speed pumps are the principal types discussed. 

Analysts The above is a formidable barrier. Analysts must use limited and uncertain measurements to operate and control the plant and understand the internal process. Multiple interpretations can result from analyzing hmited, sparse, suboptimal data. Both intuitive and complex algorithmic analysis methods add bias. Expert and artificial iutefligence systems may ultimately be developed to recognize and handle all of these hmitations during the model development. However, the current state-of-the-art requires the intervention of skilled analysts to draw accurate conclusions about plant operation. 

Astley, J., Shepherd, A., Whitfield, D. (1990). A Review of UK and International I owledge and Practice in the Selection of Process Control Operators. In E. J. Lovesey (Ed.), Ergonomics Setting Standards for the 90 s. Contemporary Ergonomics, 1990. London Taylor and Francis. 

The controller function will take on a positive pole if the process function has a positive zero. It is not desirable to have an inherently unstable element in our control loop. This is an issue which internal model control will address. 

A more elegant approach than direct synthesis is internal model control (IMC). The premise of IMC is that in reality, we only have an approximation of the actual process. Even if we have the correct model, we may not have accurate measurements of the process parameters. Thus the imperfect model should be factored as part of the controller design. 

Internal model control Extension of direct synthesis. Controller design includes an internal approximation process function. 

Haseley, P., Oetjen, G. W. Equipment data, thermodynaeumic measurements, and in-process control quality control during freeze-drying. PDA International Congress, p. 139-150, Basel 1998... 

Internal monitoring control and documentation of the decomposition respiratory digestion process by the plants... 

The sample of desorbed tritide is placed inside a quartz tube that is connected to a gas-handling manifold by a TorrSeal . A quartz sleeve with Silicon Carbide (SiC) in the annular space is placed around the end of the quartz tube, surrounding the sample with microwave susceptor. The quartz tube and susceptor sleeve are thermally insulated from the rest of the microwave cavity. An internal thermocouple measures the temperature of the sample and provides the temperature signal for process control of the desired temperature. A shine block (alumina foam), attached to the thermocouple, blocks radiant heating of the TorrSeal and the upper area of the quartz tube and manifold. An IR pyrometer is used as a secondary measure of the temperature of the susceptor, and therefore of the sample. A stainless steel shield reflects microwaves from the quartz tube not in the susceptor sleeve, eliminating the production of a plasma at low pressure in the quartz tube. 

ELISAs can be used for identification and quantitation of a biopharmaceutical product or for quantitation of impurities or contaminants as discussed previously. They can be used throughout the manufacturing process as well as in quality control or the product release stage just as they are used in all the other stages of product development. To be used for quality control, GMP practices must be followed. All methods need to be validated so that the assay s performance is documented. ELISAs should have internal quality controls to monitor assay... 

Morari and coworkers (Garcia and Morari, Ind. Eng. Chem. Process Des. Dhv. Vol. 21, p. 308, 1982) have used a similar approach in developing Internal Model Control (IMC). The method is useful in that it gives the control engineer a different perspective on the controller design problem. 

In theory, the internal model control methods discussed for SISO systems in Chap. 11 can be extended to multivariable systems (see the paper by Garcia and Morari in lEC Process Design and Development, Vol. 24, 1985, p. 472). 

Professor Luyben has published over 100 technical papers and has authored or coauthored four books. Professor Luyben has directed the theses of over 30 graduate students. He is an active consultant for industry in the area of process control and has an international reputation in the field of distillation column control. He was the recipient of the Eckman Education Award in 1975 and the Instrumentation Technology Award in 1969 from the Instrument Society of America. ... 

In fact, because of the ubiquitous expression of vimentin in tissues and its partial susceptibility to formalin fixation, some authors advocate including vimentin routinely as an internal positive control on all cases (/7). Since many useful molecules also show sensitivity to fixation or processing for histology, vimentin positivity may be used as a gauge of the general preserved antigenicity of the tissue being examined. 

Technology advances in electronics such as process control instrumentation systems, computer capabilities, programmable logic controllers, and the use of independent PC s (personal computers) at field locations for special dedicated functions present new challenges to incident investigation. Some of the advances are so rapid that the team may not have the internal expertise to determine failure scenarios, sequences, and modes. The suppliers and manufacturers of these high-tech devices are sometimes the only source of credible information on failure modes of these devices. 

Knowledge of the most common licit uses of substances in Tables I and II of the 1988 Convention, including the processes and end products in which the substances may be used, is essential to the verification of the legitimacy of orders or shipments. The most common licit uses of those substances reported to the International Narcotics Control Board are as follows ... 

The cost of appraisal in a laboratory is about measuring the laboratory performance, morritoring of the laboratory processes, doing internal quality control, internal and external laboratory audits and so on. 

G. Dishon, D. Eylon, M. Finarov, A. Shulman, Dielectric CMP Advanced Process Control Based on Integrated Thickness Monitoring, Third International CMP for ULSI Multilevel Interconnection Conference, Santa Clara, CA, pp. 267-274, Feb. 19-20, 1998. 

Even once a method is standardized, erroneous results can still be generated. As a result, it is critical to have robust quality control procedures in place. Here, careful attention should be paid to identify opportunity for in-process control measures such as internal standards, calibration, control plates, replicates and so on as opposed to post-processing data review steps. Inline QC approaches allow sources of error to be identified and remedied much more rapidly and help limit costly re-tests, or the possibility of erroneous data leaving the laboratory. 

When thermodynamics or physics relates secondary measurements to product quality, it is easy to use secondary measurements to infer the effects of process disturbances upon product quality. When such a relation does not exist, however, one needs a solid knowledge of process operation to infer product quality from secondary measurements. This knowledge can be codified as a process model relating secondary to primary measurements. These strategies are within the domain of model-based control Dynamic Matrix Control (DMC), Model Algorithmic Control (MAC), Internal Model Control (IMC), and Model Predictive Control (MPC—perhaps the broadest of model-based control strategies). 

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