Laboratory reliability check

The use of LIMS makes internal review process rapid, reliable, and concurrent with data reporting. While Tier 1 reviewers typically work with hardcopy data, Tier 2 reviewers often access appropriate LIMS modules and review sample and QC data before final results are printed. They will also review the accompanying laboratory documentation that is available in hardcopy form only. Computerized confirmation of numeric acceptance criteria, such as the recoveries of laboratory QC check samples or surrogate standards, significantly reduces time and effort during review. Tier 3 Review is usually conducted on a hardcopy final data after analytical results and support documentation have been compiled into a single package. 

The present state of the art of Cr speciation leaves much to be desired and compels to improve quality assessment. In order to meet the requirements of the directives, the reliability of the methods needs to be improved substantially. Appropriate reference materials certified for Cr(III) and Cr(VI), which are at present non existing, would provide both an effective and economical way for the laboratories to check and improve their performance which justified the production of a lyophilised solution for the certification of Cr-species [36,37]. 

Thus, we are presenting what is in many respects a completely new work. Most of the preparative methods presented here have either been verified by repetition in the author s own laboratory or checked and rechecked in those of our collaborators. We trust that the reader will benefit from the improved reliability and reproducibility that this affords. 

It is desirable that the process variable to be monitored be measured directly often, however, this is impractical and some dependent variable, that is easier to measure, is monitored in its place. For example, in the control of distillation columns the continuous, on-line, analysis of the overhead product is desirable but difficult and expensive to achieve reliably, so temperature is often monitored as an indication of composition. The temperature instrument may form part of a control loop controlling, say, reflux flow with the composition of the overheads checked frequently by sampling and laboratory analysis. 

Analytical laboratories need to check their performance with regard to the production of accurate results with satisfactory precision. The most desirable way to ensure the reliability of analytical results is the participation of laboratories into regular interlaboratory tests. An interlaboratory study has to be understood as a study in which several laboratories measure a quantity in one or more identical portions of homogeneous, stable materials under documented conditions, the result of which are compiled into a single document (IUPAC [1994] Prichard et al. [2001]). 

Figure 11(A) shows a principle sketch of a SEC set-up. The eluent (solvent) is pumped at a constant flow rate through the system. A small amount of polymer solution (typically 200 pL) is injected manually or with an autosampler. The main part comprises a set of columns (typically 3-4 columns+pre-column) typically packed with microporous styrene-divinylbenzene, porous glass, or silica. In the routine analytical laboratory it is especially useful to have a pre-column in order to collect impurities that might be present in the samples. If many different samples are to be analyzed, it is necessary to check the reliability of the columns frequently to avoid artefacts due to residues from previous samples still held on the column. In order to avoid problems, samples should be purified before they...

The previous chapters of this book have discussed the many activities which laboratories undertake to help ensure the quality of the analytical results that are produced. There are many aspects of quality assurance and quality control that analysts carry out on a day-to-day basis to help them produce reliable results. Control charts are used to monitor method performance and identify when problems have arisen, and Certified Reference Materials are used to evaluate any bias in the results produced. These activities are sometimes referred to as internal quality control (IQC). In addition to all of these activities, it is extremely useful for laboratories to obtain an independent check of their performance and to be able to compare their performance with that of other laboratories carrying out similar types of analyses. This is achieved by taking part in interlaboratory studies. There are two main types of interlaboratory studies, namely proficiency testing (PT) schemes and collaborative studies (also known as collaborative trials). 

For the most reliable results, chamber environment should be monitored continuously with instruments and techniques equivalent to those used in ambient-air monitoring networks (see Chapter 6). Calibration of instruments should follow recommendations by appropriate agencies and be checked by cross comparisons with those in other analytic laboratories. 

Applications for marketing should be sent to MHLW. The application then passes to PMDA, where the application splits into two different routes, namely (1) good laboratory practice (GLP), GCP and reliability compliance check by Office of Conformity Audit and (2) application review by Offices of New Drug or Office of Biologies. 

The SUFIR method has been successfully used in this laboratory for about ten years, implying that its reliability has been frequently checked. The only precaution concerns the timing which must be perfectly stable without disturbance caused by the data storage in alternate memory blocks. Finally,... 

This example illustrates that there is no guarantee that results are reliable, even if they are obtained by "accredited " laboratories using accepted procedures. A good way to assess the reliability of a lab working for you is to provide the lab with blind samples—similar to your unknowns—for which you know the right answer, but the analyst does not. If the lab does not find the known result, there is a problem. Periodic blind check samples tire required to demonstrate continuing reliability. 

Another significant benefit of a LIMS is the improvement of the overall quality of the laboratory. In the case of a laboratory, quality is defined as satisfying customer needs in the areas of accuracy, reliability, clarity, and timeliness of analytical information. LIMS can enhance quality in a number of ways, eg, in checking conformance to requirements, in organising and prioritizing work to ensure timeliness, in measuring laboratory performance in areas of technical quality and efficiency so as to provide continuous improvement, and in helping the laboratory to communicate deady, completely, and consistendy (16). 

How to determine any HC liquid viscosity. For the viscosity of most any HC, see Fig. A-3 in Crane Technical Paper No. 410 [3], If your particular liquid is not given in this viscosity chart and you have only one viscosity reading, then locate this point and draw a curve of cP vs. temperature, °F, parallel to the other curves. This is a very useful technique. I have found it to be the more reliable, even when compared to today s most expensive process simulation program. Furthermore, I find it to be a valuable check of suspected errors in laboratory viscosity tests. If you don t have the Crane tech paper (available in any technical book store), then get one. You need it. I have found that most every process engineer I have met in my journeys to the four corners of the earth has one on their bookshelf, and it always looks very used. 

For application as a tracer, a radioisotope is selected on the basis of availability, emitted radiation that can be distinguished from that of the analyte, an appropriately long half-life, and minimal radioactive impurities, including radioactive progeny. As discussed below, the tracer may either be purchased from a supplier as a standard or calibrated in the laboratory. An even safer procedure is to purchase a standard and check its reliability with a calibrated detector. 

On-site water-quality measurements are carried out predominantly to monitor effective purging of water at the sampling point before sample collection and to measure unstable parameters that cannot be subsequently reliably determined in the laboratory. On-site measurements can also be used to provide a check on a subsequent laboratory analysis. For example, provided that the on-site SEC is measured accurately, it can be compared with the SEC estimated from the laboratory chemical analysis by one of a number of geochemical programmes. This check can be useful for spotting major errors, such as dilution or typographical errors, as well as systematic errors in analytical methodology. 

If cylinders are to be brought into the laboratory, they should only be transported on purpose-built trolleys, to which they can be securely chained during transport. Acetylene cylinders must be kept more or less vertical, for reasons discussed in Chapter 2, section 5. The total number of cylinders in the laboratory at any one time must be kept to the minimum possible, especially for fuels and oxidants, and in routine use all cylinders must be securely chained or strapped to a bench or wall. They should be positioned for easy access and so that they will not block a rapid exit. It is perfectly feasible to run two flame spectrometers from a single acetylene cylinder, via a T junction, although individual flash-back arrestors should be fitted in the lines to both instruments. If an acetylene cylinder is used inside the laboratory, it is especially important to check for gas leaks whenever the cylinder head is changed. Don t rely on the smell of escaping gas, which will only detect fairly major leaks. Use of a paint brush and a soap solution is more reliable, as bubbles will be clearly seen if gas is escaping. 

Many laboratories use CACO-2 cells as a standard method for assessment of efflux. Since the standard CACO-2 cell assay is very well established, easy to use, reproducible and reliable the corresponding efflux assay can give valuable and helpful data for project support in a screening approach. A prerequisite for the interpretation of efflux data is a characterization of efflux transporters present in the system used and a set of standard efflux markers checked regularly (like digoxin for MDR1). 

Regarding laboratory controls, a review of laboratory notebooks and chromatograms should be done to check the reliability and authenticity of the supporting data in the methods development and testing of the clinical, bio, and stability batches. Reference standards used should be certified as standards. The FDA expects that, for bulk substances, the suitability of reference standards should be more extensive than that of bulk drug substance specifications. A comparison of analytical methods and specifications for lots of drug substance used in clinical batches and biobatches should be performed to see if any deletions or revisions to any specifications occurred. 

The development and standardization of reliable test procedures requires an ample supply of well-characterized reference materials. These samples are used for round-robin tests by participating laboratories in the method development. A reliable set of reference materials are available from the National Bureau of Standards. These special reference materials are described by Haines in this symposium series. The Bureau has packaged the materials in an appropriate size and secure container. Producer and user laboratories have these reference materials available to cross-check results and resolve differences in specification analyses. These reference standards are available at a reasonable cost. 

As mentioned earlier, the analyst must take care that the results of analysis are reliable (i.e., both accurate and precise). Good precision of determinations obtained using a given method is not enough reason for uncritical satisfaction. There are known cases in which a laboratory provided very precise results that were, however, far from the true value [8, 11, 15]. Although precision can easily be checked internally, for example, by making several repetitions of the determination and calculation of standard deviation, confidence level, and so on, checking accuracy is a much more difficult task. Several approaches are possible ... 

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