DESIGN OF A MANUFACTURING TRAIN FOR THE PRODUCTION OF RECOMBINANT THERAPEUTICS EXPRESSED IN MICROBES

Abstract

Biopharmaceutical plays a major role over convectional pharmaceutical products in curing diseases. Recombinant DNA technology has made a revolutionary impact in the area of human healthcare by enabling mass production of safe, pure and effective rDNA expression products. The main objective of the work described in this thesis was design of a manufacturing train for the production of recombinant therapeutics expressed in microbes. Emphasis has been given on design, sizing and control strategies for the key steps in the process. In case of fermentation, sizing calculations, finding out mass transfer coefficient, power consumption and jacket designing have been dealt with. For centrifuge calculation of settling velocity, g-force and throughput analysis are highlighted and for homogenizer, design features and extent of disruption have been discussed. Additionally, focus has been on discussing main issues in purification steps viz. chromatography and TFF. Sizing calculations, pressure drop, dimensions of bed, HETP and asymmetry have been discussed for chromatography and for TFF system membrane area calculation and pump selection strategies have been illustrated. Apart from these pump sizing calculations for CIP pump, pressure vessel design and Transfer panel design aspects have also been considered. Basic control strategies for plant automation have been described. In addition, various plant optimization softwares have also been described.