Validation response surface methodology

Optimization of reaction conditions for enzyme assays has traditionally been carried out by varying a single factor and studying its effect on the reaction rate, then repeating the experiment with a second factor and so on until effects of all the variables have been tested. An optimal combination of variables is selected on the basis of these experiments, and the validity of die chosen conditions is verified. Not only is this approach labor intensive, but it also is not well adapted to situations in which the effects of different variables are interdependent, as is frequently the case in enzyme analysis. This traditional empirical approach to optimization has been replaced by newer techniques of simplex cooptimization and response-surface methodology."... 

Response Surface Methodology for Validation of Oral Dosage Forms... 

Response Surface Methodology (RSM) is a well-known statistical technique (1-3) used to define the relationships of one or more process output variables (responses) to one or more process input variables (factors) when the mechanism underlying the process is either not well understood or is too complicated to allow an exact predictive model to be formulated from theory. This is a necessity in process validation, where limits must be set on the input variables of a process to assure that the product will meet predetermined specifications and quality characteristics. Response data are collected from the process under designed operating conditions, or specified settings of one or more factors, and an empirical mathematical function (model) is fitted to the data to define the relationships between process inputs and outputs. This empirical model is then used to predict the optimum ranges of the response variables and to determine the set of operating conditions which will attain that optimum. Several examples listed in Table 1 exhibit the applications of RSM to processes, factors, and responses in process validation situations. 

P. Wehrle, Ph. Nobelis, A. Cuine, and A. Stamm, Response surface methodology an interesting tool for process optimization and validation example of wet granulation in a high shear mixer. Drug Dev. Ind. Pharm., 19, 1637-1653 (1993). 

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