Quality control clinical laboratories

The effects of microsphere size distribution, drug/polymer ratio, and microsphere quality can be easily demonstrated in this laboratory model. Furthermore, as animal data and human clinical trial results are available the model becomes quite useful as a quality control method (46). 

The inherent reproducibility or imprecision of the method will have been determined as part of the validation procedure. This information can then be applied to the internal quality control programme which is designed to identify the intrusion of a bias (inaccuracy) and/or an alteration in the reproducibility of the assay. Programs for Internal quality control are most extensively developed for clinical laboratories because of the availability of suitable RMs in large batches and at an affordable cost although some level of IQC is appropriate to aU work carried out at a continuing basis see Section 6.2. 

In 1978 the International Federation of Clinical Chemistry produced a comprehensive summary of the objectives of External Quality Assessment (IFCC 1978). The first six points of Table 4.1 summarize the IFCC objectives the seventh has developed since that time and is of considerable importance in many countries where strict control over laboratories undertaking particular types of work is required by legislation or by appropriate professional organizations. 

The information requirements for products such as prolonged-release oral dosage forms will depend on whether or not it has been possible, during the development of the product, to establish an in vivo-in vitro correlation between clinical data and dissolution studies. In vivo-in vitro correlations should be attempted using product at different stages of development, but bioavailability and pharmacokinetics data from pivotal clinical studies using at least pilot-scale production materials and possibly routine production material are particularly important. Where it is not possible to establish an in vivo-in vitro correlation, additional data will be required to compare the bioavailability of product developed at laboratory scale, pilot scale, and production scale. In the absence of an in vivo-in vitro correlation, the dissolution test will be a quality control tool rather than a surrogate marker for in vivo performance of the product. 

FDA device regulation is focused on the device and the device manufacturer. CLIA, on the other hand, focuses on laboratory quality, including the quality of the laboratory test results provided by the devices used, whether developed in-house or as a test kit in commercial distribution to multiple laboratories. The programs differ substantially in approaches and in data requirements. FDA requires unique submissions for each test under its purview, evaluates both performance and labeling, and requires demonstration of analytical validity and clinical validity as appropriate. CLIA inspects laboratories using a system approach based on key probes of the operating system. CLIA requires a demonstration of analytical performance and quality control but does not require a showing of either clinical validity or clinical utility. 

An active program of surveillance of the quality of the immunostains produced must be defined. The primary elements of such a quality assurance (QA) program include procedures and policies for patient test management, quality control, proficiency testing, comparison of test results, relationship of clinical information to patient test results, personnel assessment, communications, complaint investigations, QA review with staff, and QA records. The documentation and review by the laboratory director of all QA procedures is imperative and cannot be overstressed. A brief explanation of each of the QA elements is as follows ... 

In the past, laboratories have justified the initial investment in dedicated automation on the basis of the large number of identical, repetitive operations carried out. Fixed or dedicated automation is utihzed for large quantities of standard procedures, such as those found in manufacturing environments or in clinical laboratories. Fixed automation follows a predetermined sequence of steps to perform a defined procedure although efficient, it can only perform one repetitive procedure. Robotics, however, can provide flexible automation to meet the changing needs typical of quality control and research laboratories. Flexible automation is programmed by individual users to perform multiple procedures, and can be quickly reprogrammed to accommodate new or revised procedures. In these situations, a careful assessment of the software overhead must be made before a decision to purchase is made. 

As a result of the introduction of cytometers into the hospital setting, three aspects of clinical practice have led to some general reassessment of the nature of flow analysis. First, clinical laboratories are, because of the import of their results, overwhelmingly concerned with so-called quality control. This concern has forced all cyto-metrists to become more aware of the standardization and calibration... 

Owens MA, Loken MR (1995). Flow Cytometry Principles for Clinical Laboratory Practice. Wiley-Liss/John Wiley and Sons, Inc, New York. A discussion of the theory and practice of clinical flow cytometry, with some good emphasis on quality control. 

But there are signs that simpler, less expensive LC/MS systems designed and priced for the general laboratory bench chemist, production facilities, and quality control laboratories may soon be possible. It remains to seen whether manufacturers will decide to produce these systems. Older MS systems have been purchased, attached to HPLC systems equipped with relatively inexpensive interfaces, and pressed into service for molecular weight determination as a 30,000 detector, indicating that the desire and need exists for general laboratory LC/MS systems. As prices continue to drop and technology advances work their way out of the research laboratories, the LC/MS will become a major tool for the forensic chemist whose separations must stand up in court, for the clinical chemist whose separations impact life and death, and for the food and environmental chemist whose efforts affect the food we eat, the water we drink, and the air we breathe. 

Whether the monitoring of endoxifen plasma concentrations in breast cancer patients would constitute a valid approach to optimize individual dosage and improve treatment efficacy is under scrutiny and remains to be demonstrated. In that purpose large prospective studies relating endoxifen plasma levels to clinical outcomes are as yet needed. In this perspective, it is critical to settle analytical and selectivity discrepancies between methods and laboratories and to ensure reproducible quantification results between laboratories. These concerted harmonization efforts can be carried out within the frame of an international external quality control program, which as yet, remains to be organized. 

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