Validation strategy formulation

A risk assessment is appropriate at the point of selecting a supplier for a system as well. Some aspects of risk only apply to the decision as to whether to patronize a particular supplier, such as price or potential return on investment, but other points on which a supplier is evaluated clearly represent risk factors that should be considered in formulating a validation strategy. Such elements include, but may not be limited to ... 

Drug D may be produced in both 1000- and 2000-gal batches to meet inventory requirements. Major equipment and operator instructions are the same regardless of batch size. The only difference is the amount of each ingredient charged to the make tank. With a formulation such as this, there is little likelihood that batch size is an important process variable. Nevertheless, we will be conservative and treat each size batch as a unique process. An alternative strategy would be to validate the 2000-gal process and demonstrate for the 1000-gal batch the adequacy of mixing, using, for instance, assay data. 

Validation of clinical trial formulations Validation of in vitro tests on solid dosage forms Experimental strategy for validation of industrial processes Optimization of industrial processes by evolutionary operation (EVOP)... 

If changes are required they should be planned. If possible they should be part of an experimental design so that they give information for improving the process or demonstrate its robustness. EVOP (see below) could be a useful strategy here, for validating clinical trial formulations. 

In this paper an industrial semibatch polymerisation process is considered. In order to guarantee the product quality particularly controlled reaction conditions are necessary. The general aim of this work is to ascertain optimal state and control profiles and to develop a model-based control scheme. As a first step, this paper introduces the dynamic model, which is validated with experimental data, and describes the optimisation approach. An aim of the work is to assess the possibilities of the commercial flowsheet simulator CHEMCAD in the optimisation of the performance of semibatch polymerisation processes. Finally the formulation of the mathematical optimisation problem, solution strategies and their implementation in CHEMCAD are discussed. 

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