Quality Control and Assurance

Pharmaceutical Technical, Roche Pharmaceuticals, Basel, Switzerland 

The quality of an API is determined by two factors its conformance to pre-established specifications and whether it is produced according to a documented validated process in a cGMP compliant facility. 

The API must possess appropriate chemical and physical attributes to assure that it delivers the intended pharmacological effect. The chemical attributes describe the appropriate purity and impurity limits. Impurity specifications are established from clinical toxicological studies and are also based on reasonable minimums expected from regulatory authorities and consumers. The physical attributes describe the necessary characteristics for reliable pharmaceutical processing into final dosage forms. These attributes are determined by empirical evidence from formulation trials to produce uniform and stable dosage forms of adequate bioavailability. 

The people who produce the API aire considered a critical part of the system and, as such, become part of the requirements for quality of APIs. To do their jobs effectively and to assure quality of the API, they must be properly trained and equipped. Qualified personnel must conduct the training the equipment must be of proper design and function. The supervisors of people manufacturing APIs must also be properly trained to do their jobs. Finally, there must be an adequate number of people to allow sufficient time to perform these responsibilities in a satisfactory manner. 

As in most any other manufactming enterprise, there is a quality control and/or a quality assmance department. Today, these departments are usually combined into a QM department. The role of the QM department has also advanced from check-test-decide responsibihty to being an equal partner 

Quality assurance in any applied science and engineering project is an essential task. It is a disciplined approach in the provision of systems and components of nuclear power plants. The main objectives for the vessel are to ensure that eaeh part of the vessel manufacture is assembled, inspeeted, tested and operated strictly in accordance with the performanee requirements, reliability and safety codes and the designers intent. The quahty control is those quality assurance actions which provide a means to eontrol measure and monitor the characteristics of the vessel throughout its life. The quality assurance in practice embodies formal documentation and procedures  

Acknowledgements The author acknowledges with thanks the help given by the CEGB, UKAEA and the Nuclear Consortia of UK, USA, West Germany and France. 

Waters T. C. and Barrett N. T. Prestressed concrete pressure vessels for nuclear reactors. Journal of British Nuclear Energy Society, 1963. 

Frankline Institute Laboratories, State of art of prestressed concrete pressure vessels for nuclear power reactors—A critical review of literature, USEAC Report ORNL-TM-812, Oak Ridge National Laboratory, 1964. 

Rashid Y. R. Analysis of axisymmetric composite structures by the finite element. Nuclear Engineering Design, Vol. 3, 1966, pp. 163-182. 

Clearly, the commercial or consultancy laboratory that tests sub-samples of a marketed product worth millions of pounds, or assesses the purity of pharmaceuticals, or analyses forensic samples, must have far higher levels of both accuracy and verifiability than student practical classes. There should, however, always be an effort to produce the most accurate and reliable results within the constraints of the laboratory facilities available, otherwise a lax attitude will produce work of doubtful interpretation that could mislead others, as well as giving little job satisfaction. Several books, which are more suited to the commercial sector, have been written on the quality of laboratory analysis, however some quality assurance practices could be beneficial in the smaller laboratory. A useful open-learning style book on basic concepts of quality in the analytical laboratory has been co-authored by staff at the Laboratory of the Government Chemist (Crosby et ai, 1995). 

Two important definitions are those of quality control and quality assurance. The former relates to operational techniques and activities, whereas the latter ensures that systematic actions are in place which enable confidence that the results meet the required level of quality, such as accuracy and precision. The concept of total quality control extends to areas such as management style and reduction of waste. 

Blank samples to detect impurities in the reagents or interferences  

Standard reference materials to check the accuracy of the method. 

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Although most belt manufacturers have stringent quality assurance and control procedures in place to ensure that belts will operate as designed, this does not guarantee their performance if they are not properly installed and operated under the conditions for which they are designed. Therefore, it is important to consult and follow the installation... 

In Phase III, the final dosage formulation has been established and the pivotal clinical trials are being conducted. Degradation products have been identified, so the method selectivity should be reevaluated to ensure that all degradants can be detected and quantitated. The analytical methods are completely validated, and appropriate for routine quality assurance and control purposes. The type and frequency of system suitable testing (SST) should be determined, and an excellent publication on SST for chromatography systems is available [47],... 

So PAC has indeed evolved to PAT, which encompasses not only process measurement, real-time quality assurance and control but process understanding to enable product quality by process design. The tools available to us for quality by design as defined by the FDA include ... 

Project Manager and Principal Author Quality Assurance and Control Contributing Author Contributing Author... 

The advantage of the following methods of graphical representation is the clear and simple presentation of the essential facts. Simple charts, like bar charts, x-y scatter diagrams or pie diagrams, which are also available in 3D-form are also suited to visual representation of data. They are not described because this section is devoted to treatment of multivariate data. Graphs for control charts, particulary for quality assurance and control, can be found in [FUNK et al., 1992 AQS, 1991]. 

Quality assurance is part of the regulations specified by the national standards organizations such as the Nuclear Regulatory Commission. Quality assurance applies to any material or component or a fabricated structure in the sense that their satisfactory performance in service conditions is assured. The quality assurance and control programs in Canada are contained in Canadian Standards Association document CAN3-Z 299.1-85 consisting of four parts. The four parts of the standard are such that Part 1 covers quality assurance, Part 2 refers to quality control, Part 3 refers to quality verification, and Part 4 deals with quality inspection. 

American Chemical Society publications Analytical Chemistry, Environmental Science and Technology, and the Journal of the American Chemical Society. These descriptions are usually brief and often just summarize the techniques and procedures of the method. Research reported in scientific journals is often focused on a detailed investigation of a narrow subject area, and new analytical techniques and procedures developed for the research are rarely tested in a broader context. Analytical quality assurance and control are often minimal or not described. Techniques and procedures described in scientific research journals are the beginnings of analytical methods, however, they usually require considerable development, modifications, and testing before they become widely accepted analytical methods. 

Lozenges require the same quality assurance and control measures as any pharmaceutical dosage form. Because of their unique composition, however, certain additional methods are necessary. 

The supplementary guidelines are intended to provide WHO Member States with general and minimum technical requirements for quality assurance and control in the manufacture of herbal medicines. Each Member State should develop its own national GMP for manufacturing herbal medicines that are appropriate to the country s actual situation. 

LYNN D. TORBECK is an International Consultant specializing in applied statistics and experimental design for pharmaceutical and biopharmaceutical development, quality assurance, and control validation, Torbeck Associates, Inc., Evanston, Illinois. Mr. Torbeck received the B.S. and M.S. degrees in Statistics, University of Tennessee, Knoxville, and formerly was Director of Validation World-Wide Quality Assurance, C. D. Searle (Pfizer), Skokie, Illinois. 

Internal quality assurance and control procedures are designed to guarantee the reliability of the results generated by the laboratory QA and QC ensure that the reported results contain the appropriate accuracy and precision through stringent monitoring of the analytical process, documentation of procedures and method validation. 

The standard operating procedure (SOP) manual contains the procedures validated by the laboratory it is a complete set of instructions for pre-analytical, analytical and post-analytical methodology and also procedures for quality assurance/control, chain-of-custody and security. Each step in the handling of the specimen should be evaluated, optimized where possible and documented in the SOP. Important steps in the analytical process include collection, transport and accessioning of the specimen, sample preparation, isolation and detection of the analytes, production of the report and disposal of the specimen. This chapter focuses on the quality assurance and control issues for analytical method development and validation as well as statistical representation of the data. 

Printing Worksheets and Analysis Results. After the scenario configuration is complete, required templates can be printed. These printed templates or worksheets have several functions. If printed early in the cycle, they can be used as working papers to assist in compiling the data before entering it into the shell. They can be printed at any time to reflect the current state of the database, and when the analysis is complete, they can accompany the analysis documentation for quality assurance and control requirements. The contents of the reference list can also be printed from this option. 

Contents include definitions, study planning, quality assurance and control and data quality assessment, sample acquisition, and requirements for analytical laboratories. Appendices cover a hypothetical case history for drum characterization and a survey of statistical techniques. 

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