Development Studies

The selection of an appropriate steam-sterilization cycle must be made after a carefiil study of the nature of the articles to be sterilized, the type and number of organisms present, type and size of each package, and type of packaging material used. Cycle-development studies may be conducted using fiiU autoclave loads. 

Any similar carbohydrate source from food processing (such as coconut milk or effluents from fruit canning) can be treated in this way, and there are many examples of development studies producing SCP from them. 

R. Wisnieff D. Longo, Laser Cartridge Concept Development Study , Rept No ECOM-74-0376-F, Contract DAAB07-74-C-0376, United Technologies Corp, Norwalk (1976)... 

Standifer, R. L. "Conversion of Plutonium Oxide to Plutonium Tetrafluoride with Fluorine in a Fluid Bed Reactor -Part I, Development Studies," U.S. AEC Rept. RFP-1889, Dow Chemical Company, Golden, Colorado, August 23, 1972. 

Obviously, the greater the number of subjects studied, the larger the cost. Nevertheless, having too few subjects may lead to inconclusive results, requiring that the study be repeated. Another important consideration is the availability of qualified participants. If the inclusion and exclusion criteria are very restrictive, the cost of recruiting subjects may exceed that of the actual testing. In pharmaceutical development trials, it is not unusual to see recruitment budgets of US 500- 1000 per randomized subject. Thus, for a Phase III development study with several hundred participants, often more than US 500 000 in cost is allotted to efforts to identify qualified subjects who are interested in participation. 

Dean M, Carrington M, Winkler C, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science 1996 273(5283) 1856-1862. 

Other development studies that will need to be considered include the choice of the dosage form and formulation in terms of the route of administration and the usage (and usage instructions) being suitable. The choice of the container-closure system and any dosing device also needs to be considered in this context. Data may be derived from the literature or from specific studies. 

Development studies are not normally considered to fall within the system of good manufacturing practice... 

The multistage impactor should be used for development studies into particle size assessment. Routine tests may be based on a two-stage impactor provided that this has been validated against performance in a multistage impactor. 

A spin-off of all of these task forces has been the open discussions that have led to improved design considerations and effective use of resources in the conduct of field exposure studies. These task forces have evaluated a variety of exposure measuring techniques, developed study designs for conducting studies, and performed field studies in a uniform and efficient manner. The task force protocols and designs have become models for the industry, having received valuable input and approval from the regulatory community. 

If it has not been adequately addressed during method development, study the selectivity by analysing samples ranging from pure measurement standards spiked with potential interferents, to known mixtures that match real-sample compositions. Serious interferences need to be eliminated, but minor effects can be tolerated and included in the estimation of method bias and its associated uncertainty. 

The critical period for the induction of hypospadias by finasteride in rats is Days 16 to 17 of gestation (Clark et al., 1990a). It is unlikely that other agents would have a much earlier critical period since testosterone synthesis, which is required for the development of the penile urethra, begins in the rat on Day 15 of gestation (Habert and Picon, 1984). Thus, if treatment in the embryo-fetal development study... 

Key operating parameters that may change (or be optimized) throughout a product s development and approval cycle are dissolution sampling time points and dissolution limits or specifications by which the dissolution results should be evaluated. The results generated from the dissolution test need to be evaluated and interpreted based on the intended purpose of the test. If the test is used for batch-to-batch control, the results should be evaluated in regard to the established limits or specification value. If the test is being utilized as a characterization test (i.e., biopharmaceutical evaluations, formulation development studies, etc.) the results are usually evaluated by profile comparisons. 

So-called infinity points can be useful during development studies. To obtain an infinity point, the paddle or basket speed is increased significantly (e.g., 150 rpm) at the end of the run and the test is allowed to run for an extended period of time (e.g., 60 min), and then an additional sample is taken. Although there is no requirement for 100% dissolution in the profile, the infinity point can provide data that may provide useful information about the formulation characteristics during the initial development. 

For an extended-release dosage form, at least three test time points are chosen to characterize the in vitro drug-release profile for the routine batch-to-batch quality control for approved products. Additional sampling times may be required for formulation development studies, biopharmaceutical evaluations, and drug approval purposes. An early time... 

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