CONICET | Buscador de Institutos y Recursos Humanos

In this work we present a strategy for the synthesis of multiproduct protein production processes. There are two hosts that may express each of the products as well as different downstream processing, separation and purification tasks. Moreover, alternative unit operations may be available for some of these separation tasks. The optimization of the structure of a multipurpose pharmaceutical plant with a global sequence of operations where all the recovery and purification processes needed to manufacture the products are carried out will be evaluated. A real pharmaceutical plant is analyzed; the plant manufactures recombinant proteins which are produced in two hosts: Escherichia coli and Saccharomyces cerevisiae. A global operations sequence that includes the processing requirements for the five products that will be studied will be determined. Initially, only four products are selected, a time and size factor process model is constructed and a mixed-integer nonlinear program (MINLP) calculates the optimum plant structure, subject to the production plan in the time horizon with the objective of minimizing the capital costs. Then the fifth product is incorporated and again the global optimum configuration is determined. The minimization is solved with an implementation of the outer approximation/ equality relaxation/ augmented penalty (OA/ER/AP) method. The main differences in terms of structure and plant costs when a new product is included will be compared and a qualitative analysis will also be made by contrasting the results from optimization with the real configuration consisting of five independent process sequences for each product. Given the very large quantity of novel recombinant proteins presently being approved or ?in the pipeline?, multiproduct and multihost recombinant protein production plants have recently been or are being built for the manufacture

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