Drug testing quality assurance

Another external response to concerns about MCOs has been an increased interest in measuring the quality of care they deliver [35]. This interest has resulted in the development of numerous quality indicators. One example, HEDIS (Health Plan Employer Data and Information Set), is a standardized set of performance indicators used to compare health plans. Developed by the National Committee for Quality Assurance, HEDIS measures allow employers and employees to evaluate different plans. Only a small number of HEDIS indicators are related to medication use, but more drug-related indicators are likely to be added in the future. The use of quality indicators likely will increase as the measures become more refined and tested. 

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 in vitro tests are currently employed to assure drug product quality. These include purity, potency, assay, content uniformity, and dissolution specifications. For a pharmaceutical product to be consistently effective, it must meet all of its quality test criteria. When used as a QC test, the in vitro dissolution test provides information for marketing authorization. The dissolution test forms the basis for setting specifications (test, methodology, acceptance criteria) to allow batch release into the market place. Dissolution tests also provides a useful check on a number of physical characteristics, including particle size distribution, crystal form, etc., which may be influenced by the manufacturing procedure. In vitro dissolution tests and QC specifications should be based on the in vitro performance of the test batches used in in vivo studies or on suitable compendial specifications. For conventional-release products, a single-point dissolution... 

In such cases, it is obviously advantageous to use biorelevant dissolution tests to characterize the drug substance, to compare formulations and to make a preliminary assessment of possible food effects. However, for routine quality control work, the manufacture of media containing bile components is not only rather time-consuming but may also present difficulties in terms of quality assurance and validation of the raw materials, as is the case with many chemicals obtained from natural sources. 

In the meantime, dissolution testing was more and more standardized and gained enormous impact on the fields of quality assurance and drug development in pharmaceutical industry. Several dissolution apparatus made then-way into the pharmacopoeiae, such as the rotating paddle, rotating bas-... 

The first and foremost element for GMP is the quality system. This can be divided into Quality Assurance (QA) and Quality Control (QC). QA is a total system approach. It sets out the compliance policies and procedures for all facets of drug manufacturing. QC is the practical extension of QA. The role of QC is concerned with inspection and testing of the manufacturing environment, raw materials, in-process intermediates, and finished products. 

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... 

Product specifications and their acceptable limits. Quality assurance responsibilities are essentially the same for raw materials and final products. All finished drug products are tested to determine if they meet the required quality standards. These tests help to characterize the product so that the QA/QC function can determine whether or not the product has the proper strength and is safe, pure, and efficacious, yet these tests do not build quality into the product rather, they are a measure of the product s quality. 

The checklist was developed through discussions with consultants and Quality Assurance directors and has been field-tested in final form with five successful Orphan-Drug Application submissions. 

Quality assurance activities actually begin early in the drug development process—in the analytical phase. United States requirements5 are established as early as non-clinical laboratory studies. At this early phase, the audit program concentrates on in vivo and in vitro experiments, focusing on early drug entities. These drug entities are tested under laboratory conditions to determine their potential safety risk. At this phase, human subjects (e.g., clinical studies) or field trials in animals are not involved. 

The physical and chemical characterization of any pharmaceutical product is only as reliable as the quality of the analytical methodologies utilized to assess it. Without question, the role of analytical services to the overall drug product development process is invaluable. Good analytical testing with proper controls could mean the difference between a marketable product and one that is eliminated from development. Analytical methodologies intended for characterization and/or assessment of marketed pharmaceutical products must be relevant, validatable, and transferable to manufacturing/quality assurance laboratories. 

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