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tion of phase III clinical development, the risk of study repetition must be carefully assessed against the later availability of decision-relevant data caused by waiting for the final formulation. An alternative decision would be to freeze the biokinetic specifications of the existing and not fully optimized formulation at the risk that further improvement of, e.g., stability, may not be feasible under this restriction. One of the positive developments in recent years was a trend to shorter regulatory approval times, especially in the U.S. When approval times took 24 years, most companies postponed production scale-up and commercial manufacturing preparations for this period. With current approval times of sometimes less than one year and the requirement to be ready for preapproval inspections within three months after submission, these activities must be done earlier, parallel to phase III studies, if launch delays after approval are to be avoided. Another reason for early acceptance of the final formulation is the need to complete stability studies in time to support approval and the intended shelf life at launch. Achievement of these tasks may also require earlier investments at a time when the efficacy and long term safety of the new drug are still under evaluation. The investment risk can be minimized if the company owns a multipurpose manufacturing plant capable of supplying the market for the first 23 years after launch. |
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The preceding paragraphs gave several examples demonstrating that starting new activities before the results of preceding studies are fully evaluated carries the increased risk that studies must be repeated because of inappropriate design. This risk must be carefully assessed against the chance of increased development speed. Alternative scenarios of outcomes and their consequences should be carefully considered. The final decision should be carried by broad consent. However, in many cases, it is advantageous to focus the plan on a go/no go decision and to reach this in the shortest possible time with the minimum amount of effort and data. In this way, many resources can be saved in the case of a negative outcome. In the event of a positive outcome, the missing studies can be started quickly without much loss in total time. The exact strategy selected will be specific to the project. |
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D.
Stepwise Planning and Decision Points |
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Because of the uncertainties in drug development, effort would be wasted to plan the project from beginning to end in full detail. Even if the project finally belongs to the 1015 percent of starts in preclinical development, which reach approval, the plan will most certainly be modified along the |
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