Quality assurance —stability

Quality—Chemical and pharmaceutical quality assurance (stability, impurities etc.)... 

The final element which regulations address is quality. Safety and fitness for purpose, as discussed above, are two of the characteristics that you would associate with a quality product. However, these characteristics alone would not describe a quality product. For any product or service to be considered quality you would also expect it to be reliable and consistent. Additionally in the context of medical products, quality means a requirement to demonstrate conformance to agreed specifications or applicable standards for content, purity and stability. Many organisations, from manufacturers to service providers, voluntarily apply quality assurance systems in order to more effectively meet their customers needs on a consistent basis. However,... 

Leak R.E. Leech R. (1988) Challenge tests and their predictive stability. In Microbial Quality Assurance in Pharmaceuticals, Cosmetics and Toiletries (eds S.F. Bloomfield, R. Baird, R.E. Leak R. Leach), pp. 129-146. Chichester Ellis Horwood. 

In many cases, there is difficulty in preserving residues in samples after collection and prior to pesticide analysis which coincides with a rapid further degradation and mineralization of the pesticide residues under most environmental conditions. Storage stability studies and studies on the reactivity of sample collection equipment in addition to field quality assurance procedures can help address some of these questions. Concerns are accentuated for compounds that have short half-lives in the environment but still have high acute toxicity. 

The design of an assay is, in large measure, prospective quality assurance. The factors that are likely to affect the results of the assay must be defined and controlled to the greatest extent possible. Once the general outlines of an assay have been established, key features should be examined, including optimization of sample preparation, sample stability, choice of standards, assay range, assay repeatability, optimization of separation, and optimization of detection. 

The validation process begun in Phase I is extended during Phase II. In this phase, selectivity is investigated using various batches of drugs, available impurities, excipients, and samples from stability studies. Accuracy should be determined using at least three levels of concentration, and the intermediate precision and the quantitation limit should be tested. For quality assurance evaluation of the analysis results, control charts can be used, such as the Shewart-charts, the R-charts, or the Cusum-charts. In this phase, the analytical method is refined for routine use. 

Several key issues have to be addressed in the downstream processing of biopharmaceuticals regardless of the expression system. The removal of host cell proteins and nucleic acids, as well as other product- or process-related or adventitious contaminants, is laid down in the regulations and will not differ between the individual expression hosts. The identity, activity and stability of the end product has to be demonstrated regardless of the production system. The need for pharmaceutical quality assurance, validation of processes, analytical methods and cleaning procedures are essentially the same. 

The food polymer science approach is being applied successfully in the food industry for understanding, improving, and developing food processes and products. However, to date, the glass transition generally remains more of a research and development tool than a routine quality assurance measure of food processability and stability. 

Stability of calibrants and analytes is another frequently overlooked aspect of quality assurance, which is particularly relevant to surfactants. This aspect is discussed in Chapter 4.4. Very few intercalibration studies have been performed for the surfactant types of analytes (cf. Chapter 4.5). Currently, no certified reference material is available for surfactants. The European Commission has recently tendered for production of a reference material with certified surfactant concentrations [2]. We can conclude that quality assurance in quantitative surfactant analysis is still in its infancy when compared to analysis of PCB or chlorinated dioxins. Notwithstanding this, several important achievements have been made during recent years regarding improvement of the accuracy and reliability of qualitative analysis of surfactants, which will be the subject of the following chapters. 

Quality assurance measures such as pre-analytical checks on instrumental stability, wavelength calibration, balance calibration, tests on resolution of chromatography columns, and problem diagnostics are not included. For present purposes they are regarded as part of the analytical protocol, and IQC tests their effectiveness together with the other aspects of the methodology. 

The present revised textbook on Pharmaceutical Drug Analysis caters for the much needed handbook and reference book, which is absolutely current with regard to the esteemed philosophy of analytical chemistry, an obvious solid support towards drug discovery, development, stability studies, bioavailability and pharmacokinetic studies, and above all the quality assurance of pure drugs together with their respective dosage forms. 

Regulatory bodies such as the Food and Drug Administration (FDA) in the United States require the identification of all impurities above the 0.1% level in formulated pharmaceuticals. Once identified, the structure of the impurity is typically confirmed through synthesis to provide absolute structure identification and for use as standards in subsequent quality assurance analyses. Together, LC-MS and LC-NMR play important roles in stability testing. For example, parallel analysis by LC-NMR and LC-MS was used for the rapid structure elucidation of an unknown impurity in 5-aminosalicylic acid, which is marketed for the treatment of acute ulcerative colitis and Chron s disease [57]. In another study, Fukutsu et al. [58] used a combination... 

The development process starts with a thorough planning step in which a development plan is generated by the collaboration of all stakeholders, such as quality assurance (QA), QC sourcing sites, stability, development, and regulatory functions. Planning should also include information gathering to obtain ... 

The vesicle size is an important parameter not only for in-process control but particularly in quality assurance, because the physical stability of the vesicle dispersion depends on particle size and particle size distribution. An appropriate and particularly quick method is laser light scattering or diffraction. Laser light diffraction can be applied to particles > 1 pm and refers to the proportionality between the intensity of diffraction and the square of the particle diameter according to the diffraction theory of Fraunhofer. 

The application of HPLC in routine environments, like pharmaceutical, food, or environmental analysis and particularly quality assurance, makes not only great demands on the robnstness of HPLC hardware, comprising pumps, column thermostats, and detection units, bnt in addition to the column reproducibility. Column reproducibility can be investigated at different levels of complexity Run-to-run reproducibility compares consecutive chromatographic runs, whereas long-term stability describes the column variance over several hundreds of injections. Column-to-column (batch-to-batch) reproducibility finally explores the match of independently fabricated chromatographic columns. Column characteristics that are routinely consulted for the determination of the robustness are retention, selectivity, column efficiency, and peak symmetry. 

For the cement stabilization option, a facility would be constmcted to dewater and treat the wastes. There would be a 7- to 21-day staging period of wastes for quality assurance operations. An online rate of 250 days a year was assumed. It is estimated that cement stabilization would result in a volume factor increase roughly 3.75 times the total volume of waste treated. This increase in volume is necessary to immobilize technetium present in the wastes and to achieve a final waste form that could withstand pressures of 500 pounds per square inch (psi). The cement would be placed in 4-ft by 4-ft by 8-ft steel containers that would serve as a mold and to facilitate the handling of the finished blocks (D114432, Appendix A). 

At the NcNeil Island Correctional Facility in McNeil Island, Washington, 150 yd of soil contaminated with lead were stabilized. The vendor stated that the total project costs were 75 per ton of soil treated. The costs of reagents, on-site technical support personnel, and on-site quality assurance personnel were 45 per ton (D113382, p. 16). 

The equipment sterilization charts are included in the batch production record. The equipment sterilization charts for stability batch are produced in support of this submission. These sterilization charts shall be reviewed by Quality Assurance for adherence to the sterilization cycles specified in the batch records. 

Quality attributes of food emulsions, such as appearance, stability, and rheology, are strongly influenced by the size of the droplets that they contain (Friberg and Larsson, 1997 McClements, 1999). For example, the creaming stability of an emulsion decreases as droplet size increases. Analytical techniques that provide quantitative information about droplet size are therefore required to aid in the development and production of high-quality emulsion-based food products. A variety of analytical techniques have been developed to measure droplet size, e.g., laser diffraction, electrical pulse counting, sedimentation techniques, and ultrasonic spectrometry (McClements, 1999). These techniques are used for fundamental research, product development, and quality assurance. This unit focuses on the two most commonly used techniques in the food industry, laser diffraction and electrical pulse counting. 

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