Quality control population

Pharmaceutical products are used in a variety of ways in the prevention, treatment and diagnosis of disease, hi recent years, manufacturers of pharmaceuticals have improved the quality of non-sterile products such that today the majority contain only a minimal microbial population. Nevertheless, a few rogue products with an unacceptable level and type of contamination will occasionally escape the quality control net and when used may, ironically, contribute to the spread of disease in patients. 

In assessing animal data, careful attention must be paid to the quality of the data, the incidence of spontaneous tumors in the control population, consistency if more than one study is available, and statistical validity. If the exposure route and experimental regimen employed do not agree with the most likely mode(s) of human exposure (e.g., intramuscular injection), the data must be interpreted cautiously. Consideration should be given to data on metabolism of the compound by the animal species tested, as compared with metabolism in humans if this information is known. If only in vitro data are available, only qualitative estimates may be possible because of uncertainties regarding the association between in vitro results and human or animal effects. The availability of associated pharmacokinetic data, however, may allow development of a rough quantitative estimate. 

A procedure or method maybe checked by the use of a quality control solution (often called a control), a solution that is known to have a concentration value that should match what the procedure or method would measure. The known numerical value is the desirable value in the control chart. The numerical value determined for the control by the procedure or method is charted. The warning and action limits are determined by preliminary work done a sufficient number of times so as to ascertain the population standard deviation. 

In general, it is preferable to choose excipients and processes for IR dosage forms that do not result in a formulation that requires a particular pH to function well. In the general population, the pH in the stomach is quite variable (see the subsection Choice of Dissolution Test Conditions for Quality Control ) and there is no guarantee that the dosage form will be exposed to acid, so dosage forms that require acid to facilitate release are unlikely to perform robustly in the clinical practice setting. 

Quality control of plant-made biopharmaceuticals for commercial use includes the development of a seed bank based on the transgenic plant expressing the therapeutic product, the development of a population of plants grown from a seed bank, the harvesting of these plants, and their subsequent subjection to an extraction and purification process similar to... 

The variety of examples presented here can be seen as good evidence that simulations have become a valuable, partly indispensi-able tool for the study of chemicals in solution. The inclusion of ab initio QM procedures for the calculation of forces in every step of the simulation ensures the necessary accuracy of the simulation results to predict both structural and dynamical data, thus also providing a correct picture of the molecular and supermolecular species formed simultaneously in solution. The recently developed QMCF MD methodology has overcome several of the previous problems of MD simulations, mostly not only because of the possibility to renounce any kind of empirical or fitted solute-solvent potentials, but also because of an improved embedding scheme and the use of actual atom populations for the calculation of Coulombic forces. Besides its universality of application to various chemical compounds it also offers a straightforward way of further improvement and method-inherent quality control by the employment of correlated ab initio methods, although at a price which is not yet affordable with present computational facilities, but should become feasible within a few years. 

The significance of test results depends to a considerable extent on how the physical sample was obtained. Whatever the purpose of testing, it is necessary to question whether the samples tested adequately represent the population being investigated. In many cases, one is limited by the amount of material available, there may be only one product or batch to be evaluated, but in routine quality control there is the added dimension of needing to sample repetitively in time. This means that a good measure of... 

None of the methods developed thus far can be considered ideal, especially for routine quality control purposes. Among their disadvantages are subjective readout methods, time-consuming separations, questionable specificity, and limited applicability. Recent work showing that taste thresholds for limonin are lower than had previously been assumed for significant proportions of the population emphasizes the need for a better assay method. The use of a protein specific for limonin, such as an enzyme or antibody, could provide the basis for an improved assay." (9)... 

Ideally, reference ranges consist of biomonitoring values developed according to scientifically rigorous study design and quality-control procedures (see Chapter 4). The utility of reference ranges depends on attention to reference populations and data quality. 

Analytical measurements should be made with properly tested and documented procedures. These procedures should utilise controls and calibration steps to minimise random and systematic errors. There are basically two types of controls (a) those used to determine whether or not an analytical procedure is in statistical control, and (b) those used to determine whether or not an analyte of interest is present in a studied population but not in a similar control population. The purpose of calibration is to minimise bias in the measurement process. Calibration or standardisation critically depends upon the quality of the chemicals in the standard solutions and the care exercised in their preparation. Another important factor is the stability of these standards once they are prepared. Calibration check standards should be freshly prepared frequently, depending on their stability (Keith, 1991). No data should be reported beyond the range of calibration of the methodology. Appropriate quality control samples and experiments must be included to verify that interferences are not present with the analytes of interest, or, if they are, that they be removed or accommodated. 

Because many heavy metals are toxic to man, animals and plants, it is necessary to monitor continually potable water, river water and trade and sewage effluents to check that the metal levels are below the predefined safe limits. In this way, water quality is preserved and the health of the population is safeguarded. It is because of the public health aspects that toxic limits for metals in surface waters have been introduced and those set by the European Economic Community are displayed in Table 1. It can be seen that all limits are at the trace level and in order to comply with these directives there will be a need for the regular analysis of raw and potable waters for these metals. This is the function of quality-control water laboratories. 

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... 

E239 Alzofon, J., Haley, N.J. and Wynder, E.L. (1986). Quality control in population screening for cholesterol values. Clin. Chem. 32, 1988. 

The multilocus method discovered by Alec Jeffreys has proved useful in a wide range of animal and plant species and is currently one of the most widely used fingerprinting methods in population studies. This method, using probes 33.6 and 33.15, is the only fingerprinting method for which a formal international quality control system is operated (Zeneca Cellmark Diagnostics), and offers a unique opportunity for the standardization of cell line quahty control procedures in widely distributed laboratories. 

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. 

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