Determinate error identification

The primary goals of HRA are to assess the risks attributable to human error and determine the ways of reducing system vulnerability due to human error impact. These goals are achieved by its three principal functions of identifying what errors can occur (human error identification), deciding how likely the errors are to occur (human error quantification), and, if appropriate, enhancing human reliability by reducing this error likelihood (human error reduction). The HRA process can be broken down into several steps as seen below ... 

Static reliability models are used in preliminary analyses to determine necessary reliability levels for subsystems and components. A subsystem is a particular low level grouping of components. Some trial and error is usually necessary to obtain reasonable groupings for any particular system. Early identification of potential system weaknesses facilitates corrective action. 

All of these factors determine the stress experienced by the workers and the extent to which operational errors will be recovered before disastrous consequences have ensued. In this context, hazard identification techniques, such as hazard and operability studies (HAZOP), failure modes and effects and criticality analysis (FMECA), fault trees, and others are useful in making the process environment more forgiving. 

The case study has documented the investigation and root cause analysis process applied to the hydrocarbon explosion that initiated the Piper Alpha incident. The case study serves to illustrate the use of the STEP technique, which provides a clear graphical representation of the agents and events involved in the incident process. The case study also demonstrates the identification of the critical events in the sequence which significantly influenced the outcome of the incident. Finally the root causes of these critical events were determined. This allows the analyst to evaluate why they occurred and indicated areas to be addressed in developing effechve error reduchon strategies. 

In many analyses, fhe compound(s) of inferesf are found as par of a complex mixfure and fhe role of fhe chromatographic technique is to provide separation of fhe components of that mixture to allow their identification or quantitative determination. From a qualitative perspective, the main limitation of chromatography in isolation is its inability to provide an unequivocal identification of the components of a mixture even if they can be completely separated from each other. Identification is based on the comparison of the retention characteristics, simplistically the retention time, of an unknown with those of reference materials determined under identical experimental conditions. There are, however, so many compounds in existence that even if the retention characteristics of an unknown and a reference material are, within the limits of experimental error, identical, the analyst cannot say with absolute certainty that the two compounds are the same. Despite a range of chromatographic conditions being available to the analyst, it is not always possible to effect complete separation of all of the components of a mixture and this may prevent the precise and accurate quantitative determination of the analyte(s) of interest. 

Compound Identification Number IC50 (pM) Standard Error (SE) of Fit or Standard Deviation (SD) from Multiple, Independent Determinations Hill Coefficient Maximum % Inhibition Attained Comments... 

The quantitation of products that form in low yields requires special care with HPLC analyses. In cases where the product yield is <1%, it is generally not feasible to obtain sufficient material for a detailed physical characterization of the product. Therefore, the product identification is restricted to a comparison of the UV-vis spectrum and HPLC retention time with those for an authentic standard. However, if a minor reaction product forms with a UV spectrum and HPLC chromatographic properties similar to those for the putative substitution or elimination reaction, this may lead to errors in structural assignments. Our practice is to treat rate constant ratios determined from very low product yields as limits, until additional evidence can be obtained that our experimental value for this ratio provides a chemically reasonable description of the partitioning of the carbocation intermediate. For example, verification of the structure of an alkene that is proposed to form in low yields by deprotonation of the carbocation by solvent can be obtained from a detailed analysis of the increase in the yield of this product due to general base catalysis of carbocation deprotonation.14,16... 

Near-infrared spectroscopy is quickly becoming a preferred technique for the quantitative identification of an active component within a formulated tablet. In addition, the same spectroscopic measurement can be used to determine water content since the combination band of water displays a fairly large absorption band in the near-IR. In one such study [41] the concentration of ceftazidime pentahydrate and water content in physical mixtures has been determined. Due to the ease of sample preparation, near-IR spectra were collected on 20 samples, and subsequent calibration curves were constructed for active ingredient and water content. An interesting aspect of this study was the determination that the calibration samples must be representative of the production process. When calibration curves were constructed from laboratory samples only, significant prediction errors were noted. When, however, calibration curves were constructed from laboratory and production samples, realistic prediction values were determined ( 5%). 

Eckers et al. used on-line coupled reversed-phase LC to a Q-TOF mass spectrometer, and have successfully identified trace imparities in cimetidine. In an earlier paper published by Haskins et al., they successfully identified four chromatographically unresolved reaction by-products in cimetidine, using LC-FTMS. Another example nsing fast LC coupled with a Q-TOF mass spectrometer was the identification of cimetidine-related drug substance impurities reported by Lee et al. The exact masses for six impurities were determined with an experimental error of less than 3.1 ppm. 

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