Quality performance rating

This Thesis reports on the principles and usefulness of Performance Rating as developed by the writer over a number of years. In Part one a brief analysis is made of the Quality scene and its development up to the present. The need is exposed for Performance Rating as a tool for all areas of management*. At the same time a system of Quality Control is described which the writer has further developed under the title of 'Operator Control'. This system is based on the integration of all Quality control functions with the creative functions required for Quality achievement. The discussions are mainly focussed on the general philosophy of Quality, its creation and control and that part of Operator Control which affects Performance Rating. Whereas it is shown that the combination of Operator Control and Performance Rating is both economically and technically advantageous, Performance Rating can also usefully be applied under inspection control conditions. Part two describes the principles of Area Performance Rating. *The need for, and the advantages of, Performance Rating are particularly demonstrated in Case study No.1. From this a summation expression is derived which gives the key for grouping of areas with similar Performance Rating (P). A model is devised on which the theory is demonstrated. Relevant case studies, carried out in practice in factories are quoted in Part two, Chapter 4, one written by the Quality manager of that particular factory. Particular stress is laid in the final conclusions on management's function in the Quality field and how greatly this function is eased and improved through the introduction of Area Performance Rating.

An X-ray micro-fluorescence study to investigate the distribution of Al, Si, P and Ca ions in the surrounding soft tissue after implantation of a calcium phosphate-mullite ceramic composite in a rabbit animal model

Synthetic calcium phosphates, despite their bioactivity, are brittle. Calcium phosphate-mullite composites have been suggested as potential dental and bone replacement materials which exhibit increased toughness. Aluminium, present in mullite, has however been linked to bone demineralisation and neurotoxicity: it is therefore important to characterise the materials fully in order to understand their in vivo behaviour. The present work reports the compositional mapping of the interfacial region of a calcium phosphate-20 wt% mullite biocomposite/soft tissue interface, obtained from the samples implanted into the long bones of healthy rabbits according to standard protocols (ISO-10993) for up to 12 weeks. X-ray micro-fluorescence was used to map simultaneously the distribution of Al, P, Si and Ca across the ceramic-soft tissue interface. A well defined and sharp interface region was present between the ceramic and the surrounding soft tissue for each time period examined. The concentration of Al in the surrounding tissue was found to fall by two orders of magnitude, to the background level, within similar to 35 mu m of the implanted ceramic.

Methodology for development of a physiological model incorporating CYP3A and P-glycoprotein for the prediction of intestinal drug absorption

The small intestine poses a major barrier to the efficient absorption of orally administered therapeutics. Intestinal epithelial cells are an extremely important site for extrahepatic clearance, primarily due to prominent P-glycoprotein-mediated active efflux and the presence of cytochrome P450s. We describe a physiologically based pharmacokinetic model which incorporates geometric variations, pH alterations and descriptions of the abundance and distribution of cytochrome 3A and P-glycoprotein along the length of the small intestine. Simulations using preclinical in vitro data for model drugs were performed to establish the influence of P-glycoprotein efflux, cytochrome 3A metabolism and passive permeability on drug available for absorption within the enterocytes. The fraction of drug escaping the enterocyte (F(G)) for 10 cytochrome 3A substrates with a range of intrinsic metabolic clearances were simulated. Following incorporation of P-glycoprotein in vitro efflux ratios all predicted F(G) values were within 20% of observed in vivo F(G). The presence of P-glycoprotein increased the level of cytochrome 3A drug metabolism by up to 12-fold in the distal intestine. F(G) was highly sensitive to changes in intrinsic metabolic clearance but less sensitive to changes in intestinal drug permeability. The model will be valuable for quantifying aspects of intestinal drug absorption and distribution.