(582cp) Design and Technoeconomic Analysis of a Biomanufacturing Facility for Production of a Biodefense Agent

Organophosphate (OP) nerve agents are easily weaponized and present a clear danger to soldiers in combat zones as well as civilians. Butyrylcholinesterase (BuChE), a glycoprotein naturally found in human blood at low levels, has the ability to inactivate OP agents before they can cause harm. Currently BuChE is purified from donated blood, however the high production cost (~$10,000/dose) and low supply limit its application for broad protection of our warfighters. In this project, a detailed conceptual design and economic analysis of a novel large scale biomanufacturing facility for production of recombinant BuChE is presented.  BuChE is produced transiently in wild type Nicotiana benthamiana, a relative of tobacco, using vacuum agroinfiltration.  The plants are then homogenized and the recombinant protein is recovered and purified. However, N. benthamiana lacks the enzymes needed to add certain sugars to the glycoprotein; these sugars are important to maintain an appropriate circulatory half-life of the anti-nerve agent.  An in vitro enzymatic process is designed to add these sugars to BuChE, with recombinant enzymes produced in Escherichia coli. SuperPro Designer®, a computer-based modeling tool, is used to design and simulate the unit operations, perform material and energy balances, schedule batch operations, determine the capital investment and production costs, and quantify the environmental impact of the facility.