Factor selection case studies

The intention of this section is to provide a selection of case studies of varying complexity and from different stages of chemical process plant operation. The purpose of these case studies is to indicate that human error occurs at all stages of plant operation, and to emphasize the need to get at root causes. The case studies are grouped under a number of headings to illustrate some of the commonly recurring causal factors. Many of these factors will be discussed in later chapters. 

This syndrome is characterized by proteinuria >3.5 g/day, hypoalbuminuria <3 g/dl, hyperlip-idaemia with an elevation of serum cholesterol, edema and oval fat bodies and fatty casts in the urinary sediment. A variety of disorders may produce nephrotic syndrome but, in the majority of cases, no cause is found. It is appropriate to define the selection of studies from the history and physical examination. Tests to order are antinuclear antibody, rheumatoid factor, cryoglobulins, serum complement, HBsAg VDRL serology (syphilis), protein electrophoresis of the serum and urine and HIV. If the cause is unclear a renal biopsy is done to define the glomerular lesion as treatment may on the underlying glomerular lesion. 

The first case study we will consider is the assay of aspirin together with its major degradation product salicylic acid [19], This application study was selected as the HPLC assay of aspirin is well covered in the literature and we could select factors to test from the variety of HPLC conditions used in these published methods. This test was performed using a reflected saturated factorial design requiring a total of 15 experiments. 

The next two Case Studies demonstrate typical factors that pharmaceutical companies consider when selecting a drug target. 

In chemical process development programs, discontinuities in introducing new processes, due to regulatory constraints, frequently cause the selection of suboptimal processes for development. Once established in manufacturing, even suboptimal processes can be difficult to replace (see earlier essay on Bureaucracy Reduction). Other agendas have also to be considered, as evidenced in our efforts to develop a new process for albuterol manufacture (see Chapter 5). In another case, lack of time, and perhaps also a lack of faith in the future market potential of Temozolomide, were major factors retarding the development of new processes for the manufacture of this API (see Case Study 2). 

In this case study a simulation strategy was developed to select the dosing regimen of an antibiotic. A description of the critical factors for the interaction between drug, pathogen and host is presented, along with the procedures to integrate all... 

A case-control study assembles a group of cases (people who have the disease of interest) and controls (people who do not). The exposure histories of the cases and the controls are determined to establish the extent of association between exposure(s) of interest and disease. Case-control studies compare patients with a specific disease with a control group composed of similar people but without the disease. Case-control studies attempt to identify risk factors for a disease by examining differences in antecedent exposure variables between cases and controls. For example, one can select cases of women of childbearing age with ovarian cysts and compare them with controls, looking for differences in prior use of oral contraceptives. Such a smdy was performed to determine if the then newly introduced triphasic oral contraceptives were associated with functional ovarian cysts. ... 

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