Optimal design of protein production plants with time and size factor process models.

In this work we propose an optimization model for the design of a biotechnological multiproduct batch plant. A first level of detail posynomial model is constructed for each unit, as well as decisions regarding the structural optimization of the plant. A particular feature of this model is that it contains composite units in which semicontinuous items operate on the material contained by batch items. This occurs in the purification steps, in particular with the microfilters operating between retentate and permeate vessels, and with the homogenizer and ultrafilters operating on the material contained in a batch holding vessel. Also, the unit models rely on batch operating time expressions that depend on both the batch size and the size of semicontinuous items. The model takes into account all of the available options to increase the efficiency of the batch plant design: unit duplication in-phase and out-of-phase and intermediate storage tanks. The resulting mathematical model for the minimization of the plant capital cost is a mixed integer non-linear program (MINLP), which is solved to global optimality with an implementation of the outer approximation/ equality relaxation/ augmented penalty (OA/ER/AP) method. A plant that produces four recombinant proteins in eight processing stages is used to illustrate the proposed approach. An interesting feature of this example is that it represents an attempt to standardize a plant for the production of both therapeutic and nontherapeutic proteins; the model applied is generic and can thus be applied to any such modular plant. Results indicate that the best solution in terms of minimal capital cost contains no units in parallel and with intermediate storage tank allocation.