The goal of this Phase I SBIR R&D proposal is to develop a solvent vapor mass flow monitoring instrument that will enable pharmaceutical companies to develop and monitor drug production processes based on Quality by Design (QbD) principles, supporting the FDA QbD initiative. The production of pharmaceuticals, including drugs for cancer treatment, often requires chemical processing techniques that use organic solvents. Although water is the preferred solvent, many pharmaceuticals are produced using toxic organic solvents that must be removed from the product prior to final fill/finish operations. Solvent removal from a solid form product typically includes a phase separation step followed by a drying step during which solvent vapor is removed through the application of thermal energy. Example drying operations may include vacuum drying or fluid bed drying. Alternatively, freeze drying of labile drug products involves filling vials with liquid product (containing dissolved solids) and sublimation of the solvent producing a lyophilized cake. In all of these operations the process development and process monitoring would benefit from a process analytical technology (PAT) tool that would allow continuous, real-time monitoring of the solvent mass removal rate. Currently, no PAT tool exists that provides this important monitoring capability. During the proposed Phase I R&D program Physical Sciences Inc. will perform experimental investigations that demonstrate the feasibility of developing an organic solvent vapor mass flow meter. The successful development of an organic solvent mass flow meter will enable improved process understanding and scale-up through mass balance determinations. This will lead to improved drug manufacturing and product quality and reduced production costs. This will improve the competitiveness of U.S. pharmaceutical companies and ultimately lower the cost of drug products.
The successful completion of the proposed R&D program will lead to the development of a quantitative instrument for monitoring the removal of toxic organic solvents from pharmaceutical products. The organic solvent mass flow meter will enable improved understanding of solvent drying kinetics and the development of efficient production processes based upon quality by design principles. This will result in fewer unacceptable batches and a more consistent, higher quality product which will be safer for public consumption.