Analysts automation

References A variety of mathematical methods are proposed to cope with hnear (e.g., material balances based on flows) and nonhnear (e.g., energy balances and equilibrium relations) constraints. Methods have been developed to cope with unknown measurement uncertainties and missing measurements. The reference list provides ample insight into these methods. See, in particular, the works by Mah, Crowe, and Madron. However, the methods all require more information than is tvpicaUy known in a plant setting. Therefore, even when automated methods are available, plant-performance analysts are well advised to perform initial adjustments by hand. 

Once it is determined that data exist, the next step is to begin the collection process. If sufficient thought and training is provided in the development and operation of the maintenance and operating reporting systems, much of the collection process can be automated. Automation assumes that a well-thought-out taxonomy is in place. If this is not the case, then an analyst must collect and review the records manually. In either case, the analyst must collect data from the plant sources previously discussed in order to determine the numerator (number of failures within a unique plant equipment population), and denominator (the operating time or number of demands for the equipment) of the equation to calculate failure rates. 

Method development remains the most challenging aspect of chiral chromatographic analysis, and the need for rapid method development is particularly acute in the pharmaceutical industry. To complicate matters, even structurally similar compounds may not be resolved under the same chromatographic conditions, or even on the same CSP. Rapid column equilibration in SFC speeds the column screening process, and automated systems accommodating multiple CSPs and modifiers now permit unattended method optimization in SFC [36]. Because more compounds are likely to be resolved with a single set of parameters in SFC than in LC, the analyst stands a greater chance of success on the first try in SFC [37]. The increased resolution obtained in SFC may also reduce the number of columns that must be evaluated to achieve the desired separation. 

To enable qnantitative measurements to be made, the analyst requires the ability to determine the areas or heights of the detector responses of analyte(s) and any internal standard that may be present and then, from these figures, to derive the amount(s) of analyte(s) present in the unknown sample. The software provided with the mass spectrometer allows this to be done with a high degree of automation if the analyst so desires. 

Advantages Low cost No grinding Broad applicability High b.p. solvent contamination of analyte Low investment Simple equipment Simultaneous extractions in series Low investment Simple equipment Rapid Economic solvent use Good reproducibility Low investment Simple equipment Economical Simple equipment Not traumatic Almost solvent free Concentrated analyte Rapid Low temperatures Rapid Automated Simultaneous extraction Low solvent use Rapid User friendly Automated Sequential extractions Not analyst labour intensive... 

Adequate resolution of the components of a mixture in the shortest possible time is nearly always a principal goal. Establishing the optimum conditions by trial and error is inefficient and relies heavily on the expertise of the analyst. The development of computer-controlled HPLC systems has enabled systematic automated optimization techniques, based on statistical experimental design and mathematical resolution functions, to be exploited. The basic choices of column (stationary phase) and detector are made first followed by an investigation of the mobile phase composition and possibly other parameters. This can be done manually but computer-controlled optimization has the advantage of releasing the analyst for other... 

Automated Multiple Development System (AMD2) is a handy device that automatically develops the plates, dries them, and holds the plate in a clean environment for the analyst to document the findings. Several mobile phases can be mixed and preconditioning programs exist to expose the plate to specified solvents prior to development. Upon completion of the development of the plate, the solvent is evacuated and the plate is dried for the predetermined amount of time. The advantage to this system is the user can tend to other tasks without watching the plates develop. The disadvantage is that sample application still needs to occur separate from this unit. An example of this device is shown in Fig. 13.14. 

In order to determine chemical elements in soil, samples of the soil must undergo a solid-liquid extraction. Sometimes the extracts resulting from this procedure have analyte concentrations that are too high to be measured accurately by the chosen method. Therefore, they must be diluted. At the Natural Resources Conservation Service (NRCS) Soil Survey Laboratory in Lincoln, Nebraska, an automated diluting device is used. Using this device, the analyst accurately transfers aliquots of the extract and a certain volume of extraction solution to the same container. This dilutor may also be used to pipet standards and prepare serial dilutions. 

When performing dissolution testing, there are many ways that the test may generate erroneous results. The testing equipment and its environment, handling of the sample, formulation, in situ reactions, automation and analytical techniques can all be the cause of errors and variability. The physical dissolution of the dosage form should be unencumbered at all times. Certain aspects of the equipment calibration process may show these errors as well as close visual observation of the test. The essentials of the test are accuracy of results and robustness of the method. Aberrant and unexpected results do occur, however, and the analyst should be well trained to examine all aspects of the dissolution test and observe the equipment in operation. 

While automation of dissolution sampling is very convenient and laborsaving, errors often occur with these devices because the analysts tend to overlook problem areas. Sample lines are often a source of error for a variety of reasons unequal lengths, crimping, wear beyond limits, disconnection, carryover, mix-ups or crossing, and inadequate cleaning. 

Dissolution is becoming one of the most commonly automated functions in the modern pharmaceutical development and quality assurance (QA) laboratory. To the experienced dissolution analyst the reasons seem obvious. Dissolution methods are time-consuming and require a significant amount of labor. Beyond the cost of labor, the true cost of increased regulatory requirements and documentation can be better managed through automation. Additionally, the increased pressure to... 

An automated system, by definition, should perform a required act at a predetermined point in the process and should have a self-regulating action. This implies that intervention by the analyst is not required during the procedure and that only those systems that incorporate a microprocessor or computer to control and monitor their performance can be designated as automated. Some systems may not comply strictly with this definition but are a valuable means of mechanizing laboratory activities. 

In this present book, we will look at the analytical use of two fundamentally different types of electrochemical technique, namely potentiometry and amper-ometry. The distinctions between the two are outlined in some detail in Chapter 2. For now, we will anticipate and say that a potentiometric technique determines the potential of electrochemical cells - usually at zero current. The potential of the electrode of interest responds (with respect to a standard reference electrode) to changes in the concentration of the species under study. The most common potentiometric methods used by the analyst employ voltmeters, potentiometers or pH meters. Such measurements are generally relatively cheap to perform, but can be slow and tedious unless automated. 

A number of computer software packages are available to the analyst to assist in the planning and execution of both method development and validation experiments. The attraction of these systems is that they can automate the validation process from planning the experiment to test execution to the presentation of the data in a final report form. 

Effective collaboration among the core four PA disciplines analytical, chemometrics, process engineering and control automation along with other disciplines (e.g., pharmacist, chemist, analyst, product formulators, etc.) is imperative to realize effective PAT solutions that are consistent with the intended lean manufacturing or QbD objectives. 

Taylor et al. [20] have paid considerable attention to the changing role of management, particularly with regard to the introduction of robotic systems. Management has the responsibihty to define the best areas for automation in terms of cost-effectiveness and probabihty of success. Without adequate resources, a project will fail. Laboratory managers must act as the interface between senior management and analysts to ensure that the appropriate incentives, resources and education are made available. 

---