DESIGN OF A MANUFACTURING TRAIN FOR THE PRODUCTION OF RECOMBINANT THERAPEUTIC PROTEINS AND MONOCLONAL ANTIBODIES USING MAMMALIAN EXPRESSION SYSTEMS

Abstract

Pharmaceuticals used for the treatment of various diseases in human have been usually based on the natural or synthetic organic molecules produced b: microbes or synthesized in vitro by organic chemists. However, the post genomic-er projects a remarkable change in the therapeutics market, with the realization tha proteins have many potential therapeutic advantages for preventing and curiq diseases and disorders. Among all the therapeutic proteins currentl: biopharmaceutical market is led by monoclonal antibodies. The clinical any commercial success of monoclonal antibodies has led to the need for very large-scale production in mammalian cell culture. The production process for monoclonal antibodies must be designed in such way that it meets the highest requirements with regard to consistency any reproducibility. These therapeutics usually require high doses and therefore vas manufacturing capacities. On the basis of the projected market demand in this repot the plant capacity is determined to be 2500 L for meeting a total protein requiremen of 2250 grams per year. Technology to manufacture high-dose therapeutic monoclonal antibodie (MAbs) at large scale has evolved in several ways over the last two decades. Majo cost reductions have been reported through the use of platform technologies both i upstream and downstream. The platform approach is illustrated in the present wore for the downstream processing of monoclonal antibodies. On the basis of the mas balance major equipments (bioreactor, chromatography column, crossflow systerr CIP system) that are used for the production of monoclonal antibodies are sized any designed as per the standards. Also the control loops for controlling the variou parameters in equipments are discussed. cGMP (Current Good Manufacturing Practices) compliance is the foundatio of the pharmaceutical industry and has become the benchmark for success of an enterprise involved in the development, manufacture or testing of human and animE drug products. In the present report a designing philosophy (premises design, produc and material flow, personnel flow and area classification) is proposed fot biopharmaceutical facility which is in compliance with the cGMP requirements. With the advancement in the level of automation available for process equipment there is a tremendous increase in the product yields and product quali On the basis of the S88 standards the design philosophy for software, equipment, o procedures is proposed for automating the production train. ii