I-Corps: Accelerating and optimizing biomanufacturing process development

Georgia Tech Research Corporation, Atlanta GA

Investigators

Abstract

The broader impact/commercial potential of this I-Corps project is the standardization, acceleration and optimization of process development in the biopharmaceutical industry. Currently, the production of biological molecules for human therapies is largely based on a non-standardized design of experiments that are often time consuming, labor intensive and expensive. This project develops an in-vitro / in-silico platform that standardizes the production process design following a specific framework, applicable to a wide variety of producer cell and product combinations. The in-silico mathematical model allows to explore the whole design space reducing the number of in-vitro experiments and the labor burden, and to apply model-based optimization techniques to select the best production conditions for new drugs. The acceleration of the process design has significant impact on reducing time-to-market for drugs that are needed in the market as soon as possible, for example for FDA fast track approval candidates. Additionally, the capital and operational cost reductions can help new biomanufacturers to make their businesses technically and economically feasible. This I-Corps project responds to the need for novel biomanufacturing approaches, including Quality by Design (QbD) principles and Process Analytical Technologies (PAT), which allow fast and effective process development platforms that ensure consistent product quality and reduced lot-to-lot variability. This platform incorporates QbD and uses PATs. The central component of the tool is a mathematical model that predicts dynamic nutrient uptake based on biochemical reaction networks, to quantify and characterize cell metabolism. The in-vitro component of the platform collects critical information to determine cell type/product/clone-specific parameters. These parameters give high predictive capability to the mathematical model to determine the specific media composition and feeding strategy to optimize the volumetric productivity of cell cultures producing biomolecules for human therapies. The precision of the media composition and feeding strategy reduces raw materials and operational cost, the increased volumetric productivity reduces equipment size and capital cost, and the capability to feed the exact nutrients demand for cell proliferation, maintenance and production, ensures product quality. This bioprocess optimizer represents a flexible and efficient tool that transforms, improves and accelerates conventional process development in biomanufacturing with wide applications, including biologics, cell therapies and gene therapies. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.