Human Sample Quality Assurance

If completion of sample collection and processing checklists are a requirement for the study, a plan should be developed for monitoring these source documents for compliance to SOP and guidance documents. Reviewing checklists after the first three to five samples are collected is highly recommended to identily errors in interpretation of the guidance documents early in the study and again at routine intervals. 

2 Documenting Time and Temperature from Sample Collection to Processing 

To document sample quality, assessment of sample parameters may be necessary. For example, hemolysis can interfere with some immunoassays. For urine, pH measurement, specific gravity, and microscopy analysis to assess white blood cell or bacterial contamination may be useful. 

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The company has in place numerous checks and balances to prevent human error quality assurance (QA)-driven processes require validation (secondary checks/rechecks) of operator actions, sampling/analysis, etc. 

Wise SA, Schantz MM, Poster DL, Lopez de Alda MJ, and Sander LC (2000) Standard reference materials for the determination of trace organic constituents in environmental samples. In Barcelo D, ed. Sample Handling and Trace Analysis of Pollutants Techniques, Applications and Quality Assurance, pp 649-687. Elsevier Science Publishers, Amsterdam, The Netherlands. Yoshinaga Y, Morita M, and Okamoto K (1997) New human hair certified reference material for methylmercury and trace elements. Fresenius J Anal Chem 357 279-283. 

Quality assurance and quality control (QA/QC) A system of procedures, checks, and audits to judge and control the quality of measurements and reduce the uncertainty of data. Some quality control procedures include having more than one person review the findings and analyzing a sample at different times or using different laboratories to see if the findings are similar Quantitative risk assessment (QRA) A process that relies on mathematical modeling and estimations usually derived from animal test results and the probability of risk for a chemical substance at the low dose to which the human population is normally exposed Radionuclide A nuclide with radioactive properties... 

Nuclear analytical techniques (NATs) and related isotopic tracer methods are well established as important tools in a wide variety of different kinds of environmental studies. They provide a wealth of information on sources, pathways and effects of many elements of environmental and health-related interest. Apart from being regarded as of particular strength in analytical quality assurance (IAEA, 1997), nuclear and related techniques cover studies of air particulates, solid waste products, sediments, food, water, human tissues, biomonitors and other kinds of environmental samples. 

For some applications or for quality assurance, it can be necessary to control whether instruments, surfaces, reaction tubes, or used buffers are contaminated with DNA, RNA, DNAse, or RNAse. For the detection of DNAse or RNAse, known amounts of DNA or RNA are incubated with the suspected buffers or in the tubes at 37 to 40°C for 30 to 60 min. After this, real-time PCR is performed with the untreated DNA or RNA as control. If the analysis of incubated DNA or RNA shows a higher value than the control, and the internal process control gives no hint of inhibition, DNAse or RNAse was present. For the detection of DNA or RNA contaminations, humid swab samples (in TE or phosphate-buffered saline buffer) have to be collected from surfaces or instruments and the nucleic acids extracted into the TE buffer. The buffer can also be incubated in the suspected reaction tube or pipette tip. Real-time PCR is performed with universal primers specific for cytochrome b, human DNA, or any other DNA/RNA that is identified as a source of contamination in the laboratory. 

Some aspects of conventional quality assurance discussed in Chapter 11 cannot be applied to screening processes that require data reporting soon after sample receipt. Nevertheless, statements based on measuring radionuclides—notably their concentrations relative to exposure limits or their absence—must be carefully checked in emergencies because of their impact on efforts for protecting humans and area control and remediation. 

Recently, few topics in analytical chemistry have occupied the scientific community more than the ability of chemical laboratories to reliably determine at the low parts-per-billion level the presence of Fusarium trichothecenes in environmental and toxicological samples. This paper provides a systematic approach for developing and implementing a quality assurance and quality control program for a complex analytical method in which human error and system failure can occur. The application of this approach to the problem of determining the presence of nine naturally... 

The analytical procedure that is used by this laboratory for the analysis of simple Fusarium mycotoxins will be reported separately. However, the analytical scheme is outlined in Figure 2. The method is very arduous due to several sample clean-up steps which necessitates transfer of the sample between containers. The trichothecenes and their derivatives have a tendency to adhere to glass and can be quantitatively transferred only with numerous methanol washes. While the analytical method is both sufficiently sensitive and definitive for the program requirements, the sheer amount of human manipulation required for the completion of this analysis makes it somewhat unreliable if implemented without a responsible quality assurance and quality control program. 

The next topic in this chapter introduces the two tenants of Good Laboratory Practice (GLP), quality assurance, and quality control. This is a topic of utmost importance, particularly to laboratory managers and corporate executives A good lab with a lousy GLP is a sad use of human and facility resources. Each batch of samples that are analyzed must include, in addition to the samples themselves, a matrix spike, a matrix spike dupli-... 

Consider a laboratory measuring perchlorate (CIO4) in human urine. For quality assurance, n = 5 replicate quality control samples made from synthetic urine spiked with perchlorate are measured every day. The control chart shows the mean value of the five samples observed each day over a series of days. The spike contains (x = 4.92 ng/mL, and the population standard deviation from many analyses over a long time is a = 0.40 ng/mL. 

The application of quality control procedures to ensure that satisfactory analytical performance of enzyme assays is maintained on a day-to-day basis is complicated by the tendency of enzyme preparations to undergo denaturation with loss of activity. This maltes it difficult to distinguish between poor analytical performance and denaturation as possible causes of a low result obtained for a control sample introduced into a batch of analyses. Assured stability within a defined usable time span is therefore the prime requirement for enzyme control materials, as it is for enzyme calibrators. However, specifications for the two types of materials can differ in other respects. Because the function of a calibrator is to provide a stated activity under defined assay conditions, it is not necessary for it to show sensitivity to changes in the assay system identical to those of the samples under test therefore within certain Umits, enzymes from various sources can be considered in the search for stability. However, it is the function of a control to reveal small variations in reaction conditions, so it must mimic the samples being analyzed. The preparation of enzymes from human sources is not by itself a guarantee of an effective control. For example, human placental ALP is very stable, but it differs significantly in kinetic properties from the liver and bone enzymes that contribute most of the ALP activity of human serum samples it is therefore not an ideal enzyme for use in control material for the determination of ALP. 

The quality control and assurance measures for paternity testing are similar to those for other types of human identity testing. Positive identification of samples, prevention of DNA contamination, the use of control alleles of known size, and the validation of software employed for genetic analysis and calculation are among measures common to identity testing programs. Population distribution data for the systems used must be documented. In addition, mutation frequencies of the systems used must be dociunented and used appropriately. 

Figure 3 Illustrates the problem faced by the IAEA in the broader context of their trace element laboratory intercomparison program. These data show the reported results of 16 laboratories for measurements of arsenic in the horse kidney intercomparison sample (H-8), based on various versions of atomic absorption spectrometry, optical emission spectrometry, neutron activation analysis, and Induced X-ray emission analysis. The objective of the horse kidney intercomparison was to assess (and refine) analytical methods for the determination of essential and toxic trace elements in this surrogate for human kidney (2). Kidney, as the main target organ which accumulates toxic elements, was of special Interest with respect to cadmium. Horse kidney, which contains similar levels of cadmium to the human kidney cortex, was selected for the development and maintenance of methods having a demonstrated level of quality to assure reliable biological monitoring of this element. Participants were Invited to analyze some 24 additional trace elements, however.

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