Quality control specimens

Prepare 1/20 dilutions of samples, standards, and quality control specimens using assay diluent, and add 150 pL to each of the microtiter plate wells Cover the plate with plastic film, and incubate at 37°C for 1 h... 

Table 1 Results of quality control specimen analyses...

In the analyses of blood specimens from subjects participating in bioavailability studies, the FDA instructs laboratories to include quality control specimens (QC) at each of three known concentrations (low, mid, and high). The QC specimens are processed in duplicate with each batch of subject specimens. The acceptance criteria for the batch, based on the results of these QC specimens, is that at least four of the six values must fall within a specified range about their nominal concentrations. In addition, no more than one value at each of the three QC concentration levels can be outside its acceptance range. Combining binomial and normal distribution theory, we can estimate the number of batch runs we expect to reject because of random error. 

Quality Control Samples First, many commercial kits come with quality control specimens. They will often have target values and acceptance limits provided in the documentation that comes with them. A number of points are worthy of consideration at this stage ... 

Marked differences thus exist between losses of different metals on precipitates in urine. This loss must always be accounted for when sampling urine specimens. Precipitation is a factor to be remembered also when preparing quality control specimens in a urine matrix the homogeneity of the quality control specimens has to be investigated carefully. 

In addition to the systematic inclusion of quality control specimens as part of the analytical process there are other procedures that can be incorporated into the IQC program. These tests are usually applied to methods that are undertaken on a regular, almost daily, basis. They involve the carry-forward of specimens and the calculation of batch/day means. The sensitivity of daily mean plots is increased by the CUSUM technique (http //www.westgard.com/les-sonl4.htm). 

In particular, standard specimens contain a sharp notch so that it is propagation energy rather than initiation energy which is the dominant factor. In general the standard tests are useful for quality control and specification purposes but not... 

Typical applications of such methods are the determination of trace elements in (a) the investigation of pollution problems (b) the examination of geological specimens (c) quality control in the manufacture of semiconductors. 

The establishment of performance criteria for a given tumor marker test is not a simple process because accuracy and precision are unique for each type of analyte and its application. Establishing methodological limits for accuracy, precision, sensitivity, and specificity often requires standard reference materials, quality control materials, comparative studies, and actual clinical specimens. Accuracy and precision must be measured over the analyte reportable range for which the device is intended to be used. Sensitivity and specificity must be considered with respect to the intended clinical use of the device. Also, the indications for use should be carefully considered in the design of the study protocol. The indications for class II should be to monitor residual tumor after surgery (or radiation), the recurrence of tumor, or response to therapy. A 510(k) must provide clear evidence that the device is accurate, safe, effective, and substantially equivalent to a device legally marketed in the United States. 

False-positive results with bDNA have been observed with proficiency testing specimens for HTV-1 in the College of American Pathologists HIV-1 viral load survey and HCV in the viral quality control program administered by the Netherlands Red Cross. The reason for the false-positive results with these proficiency testing specimens is not known but may be sample matrix effects. The extent to which this problem occurs with clinical samples has not been determined. However, both the HIV-1 and HCV bDNA assays were designed to have a false-positive rate of 5%. 

With respect to method application, once validation has been satisfactorily completed, there is little question that use of the analytical method in worker safety and re-entry studies falls under the full requirements of the GLP Standards. In addition, there should be an adequate level of quality control measurements taken in conjunction with the specimens so as to provide for a meaningful assessment of accuracy and precision, as well as verification of freedom from artifactual interferences. Along with these measurements there needs to be reasonably rigid data acceptance criteria in place (usually established during validation) which are consistently applied during the course of the specimen analytical phase of the study. 

TMA has mainly been used in the study of polymers. The mechanical properties study may be used to characterize a polymer as well as to assess its mechanical utility. There is an obvious application to quality control. The ability to study small specimens gives the technique a distinct advantage over more traditional methods of mechanical testing if sample size is limited. A typical TMA study has already been exemplified in Figure 11.19. 

Independent of existing intra-lot variability, a sample size of six dosage units is generally recognized to suffice the needs of quality control (QC). In very early development less than six specimens may be used to create data, but as soon as possible tests should be run with at least n = 6. It is advisable to create statistically valid and sound data for manufacturing prototypes even at very early phases of development, in order to be able to identify formulations/batches with unwanted dissolution behavior. In the early phases of a drug product s development, formulations may not be of acceptable stability. This means that stability phenomena may mask... 

Adhesion tests can be broken into two categories qualitative and quantitative. They vary from a simple Scotch tape test to a complicated flyer tape test, which requires precision-machined specimens and a very expensive testing facility. Quantitative (such as peeling) tests have been developed for coatings on plastics (12), but not to the same extent for metal-to-metal systems. The quantitative testing systems in limited use, mainly in the electronics industry, are not commonly present in production plants but have been used to aid in process development. For quality control purposes, qualitative tests for metal-to-metal adhesion (13) are usually adequate. The adhesion of some plated metal parts is improved with baking for 1 to 4 h at relatively low (120 to 320°C) temperatures. 

In summary, polarizing microscopy provides a vast amount of information about the composition and three-dimensional structure of a variety of samples. The technique can reveal information about thermal history and the stresses and strains to which a specimen was subjected during formation. Polarizing microscopy is a relatively inexpensive and well accessible investigative and quality control tool. 

The uniaxial test is widely used for quality control and formulation testing for obvious reasons. The JANAF configuration is not likely to be replaced for these purposes, especially since the backlog of information relative to the formulation art is composed primarily of data from this specimen. Grain structural analysts require more precise information, however, and when uniaxial data are obtained for their purposes, more elaborate and time-consuming tests may be conducted. 

The above are generally classified as compliance to specifications, quality control, and research and development. Specifications are requirement for an end product. Control tests are conducted by rubber product manufacturers and research and development tests are conducted for acquiring more information about processes, products, applications development and raw materials. The physical testing of rubbers often involves application of a force to a specimen of rubber and measurement of the resultant deformation or conversely application of a deformation and measurement of the required force. 

In addition to tests performed on the incoming materials, test specimens may be made to verify the strength of the adhesive joint. The quality control tests should be those that can quickly and accurately detect deficiencies in the adhesive s physical or chemical properties. ASTM lists various test methods that are commonly used for adhesive acceptance. 

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