Quality control sample analysis

A control plasma is analyzed in each series and serves as the internal quality control sample. Analysis of plasmas and urines of the ERNDIM special assays schemes (eight samples per year, four pairs at four concentration levels) serves as the external quality control program. 

Part or full revalidation may also be considered if system suitability tests or the results of quality control sample analysis are out of preset acceptance criteria and the source of the error cannot be tracked back to instruments or anything else. 

System Snitability Tests and Quality Control Sample Analysis for Ongoing Performance... 

Operating ranges should be defined for each method based on experience with similar methods, or they should be investigated during robustness studies. Availabihty of such operating ranges makes it easier to decide when a method should be revalidated. Part or full revalidation may also be considered if SST or the results of quality control sample analysis are out of preset acceptance criteria and the source of the error cannot be tracked back to instruments or anything else. 

The analysis of quality control samples is an important activity for laboratories and to make the most of the data, control charts should be used. This chapter has discussed a number of common types of control chart and described how they are set up and interpreted. 

Briefly, to assure quality assurance and quality control, samples are analyzed using standard analytical procedures. A continuing program of analytical laboratory quality control verifies data quality and involves participation in interlaboratory crosschecks, and replicate sampling and analysis. When applicable, it is advisable, even insisted upon by the EPA, that analytical labs be certified to complete the analysis requested. However, in many cases, time constraints often do not allow for sufficient method validation. Many researchers have experienced the consequences of invalid methods and realized that the amount of time and resources required to solve problems discovered later exceeds what would have been expended initially if the validation studies had been performed properly. 

Reduction in the number of chemical processing steps allows for significant reduchon in the amount of in-process and Quality Control (QC) analysis of raw materials and intermediates required in the semi-synthetic route. Reduced handling and storage/disposal of cytotoxic samples by operators and analysts reduces opportunities for hazardous exposure. 

Quality control sample, often chosen randomly, from a batch of samples and undergoing separate, but identical sample preparation and analysis whose purpose is to monitor method precision and sample homogeneity. Duplicate testing also aids in the evaluation of analyst proficiency. Volume 1(10). 

The precision and accuracy of the method was assessed by analyzing batches on three occasions (days). Each run included a duplicate set of calibration standards (CS) and a set of quality control samples (5 QC levels in 5 replicates). The following QC levels have been used 1, 3, 100, 800 2500 ng/mL in plasma and 0.25, 0.6, 25.2, 40 and 128 ng/mL in urine. The highest QC level was above the upper limit of quantification (ULQ). These samples were analyzed after 5-fold dilution in human plasma/urine prior to analysis in order to evaluate the possibility of diluting samples with concentrations above ULQ. 

At least 10 % of the samples should be quality control samples. Blank sampling cartridges should be taken to the field and returned to the laboratory for analysis however, they should not be exposed to the air. Spiked sampling media may also be similarly transported as field controls. 

Once sampling is completed, sampling media should be placed immediately in appropriate clean, sealed containers and placed on ice or dry ice for return or shipment to the laboratory. The sealed containers should be placed in a freezer maintained at -20 °C or lower until extracted. Media should not be stored for more than about two weeks. Frozen extracts may be safely stored for 90d or more. At least 10% of the samples shonld be quality control samples. Blank media should be taken to the field, briefly removed from the containers to air, and then retnmed to the laboratory for analysis. 

A control chart (quality control chart) is a graphical record of the results of the analysis of a quality control sample using a particular method. Monitoring these results over a period of time is one of the most useful ways of determining whether or not a method is in statistical control, i.e. it is performing in a consistent manner. It helps to indicate the reliability of the results. There are many forms of control chart,one of the most commonly used is the Shewhart Chart (Figure 4). 

Calibration of balances calibration of ultraviolet grating for wavelength accuracy exchange of lamps system suitability testing analysis of quality control samples and evaluation of results using control charts. 

The analysis of standards or Quality Control samples with the constraction of Quality Control charts (Figure 19.4) has been suggested as a way to incorporate quality checks on results as they are being generated. Such tests can then flag those values that may be erroneous for any of the following reasons ... 

Control samples should have a high degree of similarity to the actual samples analyzed otherwise, one cannot draw reliable conclusions on the measurement system s performance. Control samples must be so homogeneous and stable that individual increments measured at various times will have less variability than the measurement process itself. Quality Control samples are prepared by adding known amounts of analytes to blank specimens. They can be purchased as certified reference material (CRM) or may be prepared in-house. In the latter case, sufficient quantities should be prepared to allow the same samples to be used over a longer period of time. Their stability over time should be proven and their accuracy verified, preferably through interlaboratory tests or by other analysis methods. 

The frequency of the control sample analysis depends on the nature of the analysis. Successful analysis of the control samples assures that the system is performing as expected under the SOP. Validation of HPLC equipment assures that valid measurements are obtained. The quality of the analytical data can be maintained by keeping, in a safe place, records of the actual instrument conditions at the time the measurements were made. Backups should also be maintained. 

Today, a number of pharmaceutical companies dealing with HTS reach a turnover of more than 15 different assay systems a year, in which 300,000 samples or even more are tested. This confronts the scientist with more than 5,000,000 data points which point to the need for efficient automation at all stages of HTS, even in data collection, data quality control and analysis. Robots, especially large systems integrated with multiple peripheral devices, are prominent at present. 

During the analysis of the actual study samples, a standard curve using a series of spiked biological sample standards is generated with each batch of samples. The standard curve is analyzed prior to any study samples. Once analysis of study samples has been initiated, quality control samples are run at fixed intervals throughout the analytical run. An acceptable frequency depends on the method being used, but a common approach is to run a quality control sample after every 10 study samples. Quality control samples are spiked biological sample standards that are prepared at the time the actual study samples are collected and stored under the same conditions as the study samples. Quality control samples are usually prepared at two or three concentrations that cover the expected study sample concentrations. 

Validation procedures, methodology and acceptance criteria should be specified in the analytical protocol, and/or the SOP. All experiments used to support claims or draw conclusions about the validity of the method should be described in a report (method validation report). Any modification of the method during the analysis of study samples will require adequate revalidation. The results of study sample determination should be given in the analytical report together with calibration and quality control sample results, repeat analyses (if any), and a representative number of sample chromatograms. 

Recommended analysis and acceptance criteria apply to each sample concentration HQC = high-quality control sample LLOQ — lower limit of quantification sample LQC = low-quality control sample MQC — middle quality control sample ULOQ — upper limit of quantification sample) %CV — percent coefficient of variation %RE — percent relative error [4]... 

This should be determined using validation samples, and it is ideal if these are the same samples that will be used as quality control samples in the sample analysis phases of the studies. Choice of the concentrations will be determined by the use of the assay and, as previously mentioned, assay kit components will usually need to be supplemented by additional QC samples, either due to different concentrations or specific matrix requirements. The concentrations may be driven by the analytical range of the method, or the clinically relevant range expected to be important when analyzing test samples, or both. 

The most common method would be off-line or grab samples, which are taken intermittently and transported to the laboratory for analysis (Figure 9.1(a)). The procedure can be slow and the process may be finished before the results are available. This is more suited to quality control samples taken at the end of the process. Increasingly, samples can be taken at-line (Figure 9.1(b)). These types of samples are also taken intermittently but analysed in an instrument that is very close to the process, i.e. in the plant itself. The next type of sample (on-line samples) are taken from the process (usually automatically) and transferred directly into the analytical instrument for analysis without human intervention (Figure 9.1(c)). Pretreatment of the sample may also be carried out automatically as part of the assay. 

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