Laboratory operations assay design

True process analytics are based on automated systems. Automated instruments must be smaller, more rapid and robust than laboratory instruments and designed for unattended operation. Those most commonly used are based on spectroscopic, separation and electrochemical analytical techniques. Many of these are incorporated into or combined with flow injection analysis (FIA) systems in order to work well. Not all analytical methods lend themselves to automation. Analyses involving gases and liquids are most successfully automated while those using solid samples are most difficult to automate. And there will always be certain assays that are too complex or too costly to automate. 

A validated assay, therefore, depends on the eharaeteristies of assay design that ensure the results. This leads to a robust assay (not easily affected by physieal faetors, operators, or geographical location where used or where samples came from). Such assays generate data that ean be compared direetly irrespeetive of whieh laboratory uses it, and to what population of animals it is applied. 

If a laboratory was fully confident in a particular assay it might submit it for testing by several laboratories, which would give a measure of how reproducible the assay was in a wider sense with different operators and equipment. For an as.say to succeed in this type of exercise it would have to very robust. For example pharmacopoeial monographs are designed, in theory, to be sufficiently robust to be reproduced relatively easily by many laboratories. Flowever, the tolerances for the precision of such assays might be quite wide. 

The information in this chapter applies specifically to the first element sample preparation. The sample preparation steps are usually the most tedious and labor-intensive part of an analysis. By automating the sample preparation, a significant improvement in efficiency can be achieved. It is important to make sure that (1) suitable instrument qualification has been concluded successfully before initiation of automated sample preparation validation [2], (2) the operational reliability of the automated workstation is acceptable, (3) the analyte measurement procedure has been optimized (e.g., LC run conditions), and (4) appropriate training in use of the instrument has been provided to the operator(s). The equipment used to perform automated sample preparation can be purchased as off-the-shelf units that are precustomized, or it can be built by the laboratory in conjunction with a vendor (custom-designed system). Off-the-shelf workstations for fully automated dissolution testing, automated assay, and content uniformity testing are available from a variety of suppliers, such as Zymark (www.zymark.com) and Sotax (www.sotax.com). These workstations are very well represented in the pharmaceutical industry and are all based on the same functional requirements and basic principles. 

Lacking assay accuracy may also stem from the fact, that most LC-MS/MS methods used in clinical laboratories are still locally designed laboratory-developed tests operating on very heterogeneous instrument configurations. Consequently,... 

The drawbacks of discrete analyzers are their mechanical complexity and high cost of operation. Sample cups, disposable cuvettes, rotors, and prepacked reagents increase the cost of individual assays above the acceptable limit for the strained budgets of most clinical laboratories. In addition, these machines are seldom used outside the clinical laboratory, because they are designed to handle three dozen of the most frequently required clinical tests. The advantages of the discrete approach are the ability of some of these instruments to perform assays via random access—which allows sequential assay of diverse analytes at will—and the capability of stat operation, which yields the analytical readout within 5-10 min after the machine has been switched on and a sample has been inserted by a technician. 

Integrated Raman systems can be classified as instruments designed for the research laboratory, for routine analysis, for process control, and for portable, field-deployable applications. Research laboratory instruments offer new and state-of-the-art capabilities in exchange for compromised reliability and frequent need for support from a Raman expert. Research laboratory instruments are extremely adaptable to address unanticipated measurement needs. Routine analysis instruments provide limited flexibility with good reliability. They are operationally simple and contain enough Raman expertise built in for technicians to carry out repetitive assays efficiently and reliably. Process control instruments are typically fiber optic Raman systems that have been hardened to perform in the more challenging environmental conditions typical of a chemical production facility. A process control instrument usually runs continuously in a fully automated mode. There... 

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