Study planning phase

A specified number of residue trials must be conducted for each crop to provide sufficient data for each active ingredient. 

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When an oil or gas field has just been discovered, the quality of the information available about the well stream may be sparse, and the amount of detail put into the process design should reflect this. However, early models of the process along with broad cost estimates are needed to progress, and both design detail and cost ranges narrow as projects develop through the feasibility study and field development planning phases (see Section 12.0 for a description of project phases). 

In Japan, if there are no Phase II clinical trials of equivalent duration to the planned Phase III trials, conduct of longer duration toxicity studies is recommended as given in Table 2. 

The GLPs also state that the QAU must inspect each critical phase of the study. In conducting inspections to assess the analytical chemistry phase of these studies, it is important for the QAU to identify how that phase fits into the overall study plan. 

For studies that have delegated responsibilities to a PI, the study director will rely on that individual to ensure that relevant phase)s) of the study are conducted in accordance with the study plan, relevant SOP, and principles of GLP. The PI should contact the study director when event(s) occur that may affect the objectives defined in the study plan. All communications should be documented. Communication between the study director and the QA is required at different stages of the study. For instance (1) to review study plans (2) to review new and revised SOPs (3) attendance of QA personnel at study initiation meetings and in resolving potential problems related to GLP (4) by responding to inspection and audit reports promptly (5) by indicating corrective action and (6) by necessary liaison with QA staff, and scientific and technical personnel. In certain unforeseen conditions, change of study director becomes essential. Under such conditions, replacement of the study director should take immediate effect. 

Replacement Because the study director has responsibility for the overall conduct of a study according to the GLP principles, he or she must ascertain that every phase of a study fully complies with these principles, that the study plan is followed faithfully, and that all observations are fully documented. Theoretically, this responsibility can only be fulfilled if the study director is present during the whole study. This is not always feasible in practice, and there will be periods when replacement may be necessary. Although the circumstances under which a study director would be replaced are not defined in GLP principles, they should be addressed by the facility SOPs. These SOPs also should address procedures and documentation necessary to replace a study director. 

This function, as has already been stated, is an independent review. The responsibilities here start with a review of the study plan and continue through the review of the study in the in-life phase, data audits, and the final study report audit. 

In the planning phase of a method comparison study, one should consider the size of the medicaUy significant difference or critical difference that should be detected at a given concentration TO-i jjgetc (see Analytical Goals)... 

Phase 3 studies are performed after evidence of the effectiveness of the drug has been obtained. These are expanded clinical trials intended to gather additional data regarding safety and effectiveness, as well as to determine the risk-benefit relationship of the drug. Phase 3 studies may include a range from several hundred to several thousand patients. Often a bioequivalence (BE) or bioavailability (BA) study is included to demonstrate comparability of the proposed market formulation to the clinical formulation(s) used in the previous safety and efficacy studies. Plans for NDA preparation are initiated in anticipation of favorable clinical results from the phase 3 trials. 

The necessity of the project must be evaluated. This can only be done after review of all documents, the study plan, and current data, and discussion with the current development leaders for the agent. It may be that sufficient knowledge has already been created for the project to proceed. It is important to address the trade-offs of doing versus not doing the simulation project. If, for example, a Phase 2 study has already documented efficacy, the dosing strategy, optimal patient selection for Phase 3, and Phase 3 would then be executed as a formality and for assessment of adverse events. In that case a modeling and simulation may not be necessary. 

In 1999, DOE issued a solicitation seeking proposals to evaluate the technical and financial feasibility of projects known as EECP (early entrance coproduction plant). These plants are aimed at demonstrating the operations of advanced CTL technologies in integrated mode at pre-commercial or commercial scale units. The study was structured in three phases Phase I (concept definition and research/development and testing planning). Phase II... 

The possibility of assigning study parts (or phases) to test sites different from the Study Director s test facility increases the flexibility in study planning and conduct, while at the same time it will be increasing transparency for the purpose of reconstructability. A differentiation has to be made, however, between full test facilities, where whole studies can be conducted from beginning to end, and test sites, where only parts of a study will be performed and where the GLP Principles have only to be complied with as far as its responsibilities in study conduct would require. In this differentiation GLP wants to achieve clarity in terms of the respective requirements for a test facility, where the full GLP Principles will apply, as opposed to those for a test site where not all of the GLP Principles might necessarily be applied. 

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