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      PRELIMINARY MODELING OF AN INDUSTRIAL RECOMBINANT HUMAN ERYTHROPOIETIN PURIFICATION PROCESS BY ARTIFICIAL NEURAL NETWORKS

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          Abstract

          Abstract In the present study a preliminary neural network modelling to improve our understanding of Recombinant Human Erythropoietin purification process in a plant was explored. A three layer feed-forward back propagation neural network was constructed for predicting the efficiency of the purification section comprising four chromatographic steps as a function of eleven operational variables. The neural network model performed very well in the training and validation phases. Using the connection weight method the predictor variables were ranked based on their estimated explanatory importance in the neural network and five input variables were found to be predominant over the others. These results provided useful information showing that the first chromatographic step and the third chromatographic step are decisive to achieve high efficiencies in the purification section, thus enriching the control strategy of the plant.

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          Most cited references53

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          An accurate comparison of methods for quantifying variable importance in artificial neural networks using simulated data

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            Biopharmaceutical benchmarks 2006.

            Gary Walsh (2006)
            The rate of biopharmaceutical approvals has leveled off, but some milestones bode well for the future.
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              Advances in on-line monitoring and control of mammalian cell cultures: Supporting the PAT initiative.

              In recent years, much attention has been directed towards the development of global methods for on-line process monitoring, especially since the Food and Drug Administration (FDA) launched the Process Analytical Technology (PAT) guidance, stimulating biopharmaceutical companies to update their monitoring tools to ensure a pre-defined final product quality. The ideal technologies for biopharmaceutical processes should operate in situ, be non-invasive and generate on-line information about multiple key bioprocess and/or metabolic variables. A wide range of spectroscopic techniques based on in situ probes have already been tested in mammalian cell cultures, such as near infrared (NIR), mid infrared (MIR), 2D fluorescence and dielectric capacitance spectroscopy; similarly, the electronic nose technique based on chemical array sensors has been tested for in situ off-gas analysis of mammalian cell cultures. All these methods provide series of spectra, from which meaningful information must be extracted. In this sense, data mining techniques such as principal components regression (PCR), partial least squares (PLS) or artificial neural networks (ANN) have been applied to handle the dense flow of data generated from the real-time process analyzers. Furthermore, the implementation of feedback control methods would help to improve process performance and ultimately ensure reproducibility. This review discusses the suitability of several spectroscopic techniques coupled with chemometric methods for improved monitoring and control of mammalian cell processes.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                bjce
                Brazilian Journal of Chemical Engineering
                Braz. J. Chem. Eng.
                Brazilian Society of Chemical Engineering (São Paulo, SP, Brazil )
                0104-6632
                1678-4383
                September 2015
                : 32
                : 3
                : 725-734
                Affiliations
                [02] Marianao La Habana orgnameInstituto Superior Politécnico José Antonio Echeverría orgdiv1Facultad Ingeniería Química orgdiv2Grupo Análisis de Procesos Cuba ogozaquimica.cujae.edu.cu, osvaldogoza@ 123456gmail.com
                [01] Playa La Habana orgnameCentro de Inmunología Molecular Cuba rosahcim.sld.cu, ojito@ 123456cim.sld.cu
                Article
                S0104-66322015000300010
                10.1590/0104-6632.20150323s00003527
                5cc8e0fe-7147-4aa7-8dd0-a83ad12f8cd5

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 02 December 2014
                : 26 May 2014
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 35, Pages: 10
                Product

                SciELO Brazil

                Categories
                Bioprocess Engineering

                Neural network,Erythropoietin,Chromatographic purification,Modeling

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