Process measurements reliability

The assessor should also find out whether an effective testing program is in place to help ensure the serviceability of process measurement equipment. The successful toller should have an established calibration program to address the accuracy of critical measurement equipment. Safety critical process parameters should be monitored and critical process equipment should automatically interlock when monitoring instrumentation detects safety critical deviations. Interlocks should either facilitate a remedy to the critical deviation or bring the process to the zero energy state. These instruments and interlocking devices should be routinely tested to ensure operational reliability. 

In order to study the influence of ions on the deposition process, a reliable quantification of the ion flux and energy is imperative. This flux cannot be determined directly from the detected number of ions in an lED as measured by means of QMS, for three reasons [332]. First, the orifice size decreases during subsequent measurements due to deposition of a-Si H on the edges of the orifice. Second, due to the limited acceptance angle of the mass spectrometer system, only a fraction of the ions that arrive at the substrate is actually detected. This fraction depends on the type and number of interactions that an ion experiences while traversing... 

A Altered flow cell offers the advantage of removing particles or bubbles from the optical path. This makes reliable process measurements possible in difficult enviromnents where particles and/or bubbles abound. A fermenter is one example of such an environment. 

Particles also cause the scattering of light in a process sample. Filtering probes and cells are available, which can eliminate most particles and bubbles from the optical path and make reliable process measurements possible for difhcult sample matrices (see e.g. Section 4.7). If particle formation is inherent, like insoluble excipients in dissolution studies of tablets, an ATR UV probe may be considered. 

Experimental Analysis. The most reliable process measurement is the oscillator frequency from the PAAR densitometer. Along with the frequency, the temperature is also measured ( 0.05 C). These two states are used to interpolate the solute concentration. CSD weight percent information and obscuration measurements were obtained from the Malvern Particle Sizer. Approximately 500 concentration data points and 200 CSD and obscuration measurements were recorded during a run of about 80 -100 minutes. Therefore, the dynamics of the system were well monitored, i.e., the time constant of the crystallizer is much larger than the sampling time. We have performed 25 experimental runs. This section summarizes the analysis of a single, typical experiment. 

Among several techniques possible to design process measurement tools, those based on spectroscopic techniques such as near-infrared (NIR), infrared (IR), Raman, terahertz (THz), fluorescence and UV-Vis absorption offer obvious advantages for PAT owing to their speed, compactness and versatility. Spectroscopic assessment yields chemical information such as content of active pharmaceutical ingredient (API) or of the relative concentration of different ingredients in a suspension, a blend, a composite preparation/formulation. However, physical information may also be obtained that is directly or indirectly related to, for example, particle size, porosity and density. Physical information is particularly valuable in characterisation of manufacturing processes and for reliable prediction of finished product properties. 

In addition to keeping the controllers tuned, other methods are available to improve the quality and reliability of process measurements. Overall process balance calculations and the use of predictor/estimator filters (e.g., Kalman filters) can help to improve the quality of measurements. These better-quality measurements are contributing to better control of performance, which will be discussed in more detail in the following subsections. 

Interlock testing is performed on a periodic basis, usually every 12 months, following detailed written test procedures. The test procedure for each safety interlock defines the actions, including the approval system and the mechanical work required to ensure reliability. These procedures cover the testing activity from the process measurement device to the final element, which is often a control valve. [26]... 

Good Chemical Yield. If the yield is too low, the loss suggests a sample processing problem, and measurement reliability is decreased. Many radio-analytical laboratories impose a cutoff at a minimum chemical yield value such as 50% for an analysis to be acceptable. 

What are the types of problems that need to be addressed by measuring reaction rates The answers to this question are very diverse. For example, in the testing of catalysts, a new catalyst may be evaluated for replacement of another catalyst in an existing process or for the development of a new process. Accurate, reliable laboratory reaction rate data are necessary for the design of an industrial reactor... 

LOD LOD=concentration derived from the smallest measure that can be detected with a reasonable certainty for a given analytical procedure LOD=lowest concentration of an anal)de that the analytical process can reliably detect. 1 [10]... 

Ultrasonic nebulization This has been applied since the early work on ICP-AES [151], Both nebulizer types where the sample liquid flows over the nebulizer transducer crystal and types where the ultrasonic radiation (at 1 MHz frequency) is focussed through a membrane on the standing sample solution have been used. When applying aerosol desolvation the power of detection of ICP-AES can be improved by a factor of 10 by using ultrasonic nebulization. This specifically applies to elements such as As, Cd and Pb, which are of environmental interest. However, because of the limitations discussed in Section 3.2, the approach is of particular use in the case of dilute analytes such as in water analysis [150]. Additional fine detailed development, however, is regularly carried out, as with ICP-AES the process is crucial for elements such as Cd, As and Pb for which threshold values in fresh water samples can just still be measured reliably with this type of sample introduction. Such a development is the microultrasonic nebulizer (pUSN) operated with argon carrier gas, as described by Tarr et al. [410]. 

The SEDEX system (Sensitive Detector of EXothermic processes) was developed by Hakl (176-178) for investigating the thermal decomposition of compounds undergoing exothermic processes. It features (1) a high sensitivity (2) a mode of operation conformable to plant conditions (3) economy, for example, low cost of apparatus, simultaneous measurements, reliable data, and so on and (4) a simple way to operate and interpret the results. 

Success in monitoring process and outcomes depends on the reliability of the indicators which are used. Five criteria should be considered when selecting indicators usefulness, clarity, measurability, reliability and validity [18]. Issues relevant to the quality of indicators will be briefly considered here. 

The radioanalytical chemist who is responsible for such monitoring selects or designs procedures that meet the client s specifications of sample type, list of radionuclides, measurement reliability and sensitivity, and response time. The analyst also considers the limits imposed by prescribed sample size, solution volume appropriate for chemical separation, and radiation detection instruments at hand. Potentially applicable procedures are selected for these criteria by literature review and then evaluated in a methods development and testing process. A chemical separation procedure can be devised either by selecting the most applicable published method and introducing any needed modifications or by combining pertinent separation steps. 

The applicability of radioanalytical chemistry methods is tested initially with radioactive tracers and realistic mock samples. A tracer that can be measured reliably and conveniently, such as a radionuclide that emits gamma rays, is preferred. If initial tracer tests are successful, tests are repeated with the media that will be analyzed. These tests must demonstrate that the radionuclide of interest is recovered consistently with good yield and that no interfering radionuclides or solids remain. The extent of reproducibility is determined by analyzing acmal samples in replicate for chemical and radionuclide yield. Replicate samples are identical samples from the same batch, processed and counted separately to assess the variability or uncertainty in the analysis. The recommended test statistic for a duplicate analysis is computed using Eq. (10.27) ... 

The measurement "reliability" requires that a system be successful for an interval of time. While this probability is a valuable estimate for situations in which a system cannot be repaired during a mission, something different is needed for an industrial process control system where repairs can be made, often with the process operating. 

Both measures of harm and assessments of failures in the process of care may reflect overall levels of safety. Failure to give appropriate care may or may not lead to harm, but it certainly seems reasonable to class these failures under the general heading of safety. These process measures however, seem similar if not identical to broader quality measures of effectiveness, reliability and efficiency captured in numerous studies of the quality of care. Does this mean that safety measures are nothing more than quality measures under another name Not exactly, though when we examine the level of process rather than outcomes, the same measures may reflect both safety (in the sense of potential for harm)... 

In the first case, the achievable SIL is intrinsic to the equipm t in the second case, although the intrinsic quahty of the equipment is inqiortant, the achievable SIL is also affected by the testing regime. This is important in the process industry sector, where achievable SILs are liable to be dominated by the reliability of field equipment - process measurement instruments and, particularly, final elements such as shutdown valves - which need to be regularly tested to achieve required SILs. 

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