Sample management

Two rules have been kept in mind when thinking about samples for biomarker discovery and primary validation. These rules are designed to reduce the complexity of discovery experiments by reducing the number of artifact and false markers that are the result of poor sample collection and handling processes, which often contribute to problems in statistical data analysis. These artifact markers can also mask real biomarkers and cause them to be ignored or missed in the early stages of the project. 

Rule 1 All samples have been treated exactly the same. This means that a protocol has been developed for the entire process of sample collection, storage, and use. The defining of the sample collection protocol must be done with three main points in mind  

In the development of the sample collection protocol, one must keep in mind what is reasonable in the real world. If blood samples are being collected by a nurse in a hospital (for example) it would be unreasonable to think that the samples could be aliquoted and frozen 20 min after collection. 

Example Sera proteomic study. Here is an example of a sample collection protocol that is being used for sera proteomics study in a hospital. 

The second issue is that some important biomarkers are present in low concentrations and are near the limit of detection the loss of even a small amount of these molecules may cause them not to be observed in the sample and thus the information about them will be lost. 

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FIGURE 4-8. Sample Management Grid PSM Elements/Primary Responsibility and Location... 

Exhibit 3-5. Sample Management Process Flow Chart for Xmple, Inc. Developing and Issuing a PSM Procedure... 

Data analysis should focus on the development or refinement of the conceptual site model by analyzing data on source characteristics, the nature and extent of contamination, the contaminants transport pathways and fate, and the effects on human health and the environment. All field activities, sample management and tracking, and document control and inventory should be well managed and documented to ensure their quality, validity, and consistency. 

The receiving, unpacking, and aliquoting of various actinide materials is the primary function of sample management (SM) in the actinide analytical chemistry group at Los Alamos National Laboratory. Upon receipt of a sample shipment, the contents of each container must be closely validated with the labeling on the container and with the paperwork that accompanies the shipment. Any discrepancy must be immediately rectified. 

For any new excipients, APIs or drug products (where new does not necessarily mean novel, but new to the receiving site) there are additional testing criteria, e.g. supplier audits, third-party contract laboratory audits, analytical method transfers, sample management/tracking, etc. For those key excipients, where there is on-site historical experience, it still behoves both parties to check whether the local grade/supplier used by the CMO is equivalent to that used by the supplier (Worsham, 2010). There are many examples of differences in excipient physical properties, e.g. particle size, which have been attributed to different excipient sources that could ultimately impact on the performance of those excipients in formulated products (Frattini and Simioni, 1984 Dansereau and Peck, 1987 Phadke et al., 1994 Lin and Peck, 1994). 

Ueno, G., Hirose, R., Ida, K., Kumasaka, T. and Yamamoto, M. (2004). Sample management system for a vast amount of frozen crystals at SPring-8. /. Appl. Crystallogr. 37,867-873. 

Although in principle it is possible to simply use several GC instruments each equipped with a sample manager and a separate PC, this is really not efficient because it is expensive, and at the same time data handling becomes tedious. The first successful construction consisted of two GC instruments (e.g., GC instruments and data bus HP-IB) are commercially available from the firm Hewlett-Packard, Waldbronn, Germany), one prep-and-load sample manager PAL) (commercially available from CTC, Schlieren, Switzerland) and one PC 102). 

Recently, this system has been extended to include three GC instruments operated by one PC (Fig. 12) 103,104). Experience has shown that a single sample manager for all three GC instruments may cause problems because it is difficult to construct identical columns 104). Therefore, three sample managers were employed... 

Sample management and sample plans Stability program Packaging and labeling Labeling controls and approvals Package development... 

Non-sampling errors can be categorized into laboratory error and data management error, with laboratory error further subdivided into measurement, data interpretation, sample management, laboratory procedure and methodology errors. 

We can easily quantify measurement error due to existence of a well-developed approach to analytical methods and laboratory QC protocols. Statistically expressed accuracy and precision of an analytical method are the primary indicators of measurement error. However, no matter how accurate and precise the analysis may be, qualitative factors, such as errors in data interpretation, sample management, and analytical methodology, will increase the overall analytical error or even render results unusable. These qualitative laboratory errors that are usually made due to negligence or lack of information may arise from any of the following actions ... 

Sample management error improper sample storage analysis of samples that have reached the end of their holding time misplaced or mislabeled samples sample cross-contamination... 

Representativeness Sampling design error Field procedure error Data interpretation error Sample management error Data management error... 

The general process of sample transformation into data is the same at every environmental laboratory. The differences are primarily in the manner various tasks are performed by laboratory personnel. To assure the quality of produced data, every laboratory must develop, implement, and maintain a quality system that is documented in the Laboratory QA Manual. The implementation of specific tasks related to sample management, analysis, and quality system, which may be different at different laboratories, is addressed through a set of laboratory s own SOPs. A full service laboratory has dozens of SOPs, describing every laboratory procedure and task from sample receiving to invoicing. The SOPs are updated as necessary and undergo internal review and approval. 

Example 4.1 Sample management errors during sample receiving... 

Consistent QA measures implemented at the laboratory prevent most of sample management errors during storage ... 

The chemist also examines sample management records, such as the COC Forms, Laboratory Cooler Receipt Forms, and project records of communications with the laboratory to establish whether errors may have compromised the representativeness or legal defensibility of the samples. Review of sample management records enables the chemist to answer the following questions ... 

The chemist interprets the results of trip and equipment blank analyses to identify sample management errors during sampling, sample handling, and decontamination procedures and to determine whether these errors may have affected the collected sample representativeness. The chemist qualifies the data according to the severity of the identified variances from the SAP specifications and may even reject some data points as unusable. Example 5.8 shows a logical approach to the interpretation of the trip and equipment blank data. 

Sample Management Yes No (Describe the cause and list affected samples) NA... 

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