Continuous Production of Five Active Pharmaceutical Ingredients in Flexible Plug-and-Play Modules: A Demonstration Campaign
Luke Rogers, N.E.B. Briggs, Ramona Achermann, Andrea Adamo, Mohammad Azad, David Brancazio, Gerard Capellades, Gregory Hammersmith, Travis Hart, Joseph Imbrogno, Liam Kelly, Guohua Liang, Clémence Neurohr, Kersten Rapp, M. Grace Russell, Carter Salz, Dale A. Thomas, Lukas Weimann, Timothy F. Jamison, Allan S. Myerson, Klavs F. Jensen
Abstract
Traditional pharmaceutical manufacturing is based on a complex supply chain that is vulnerable to spikes in demand and interruptions. Continuous pharmaceutical production in compact modules is a potential solution that allows for drug manufacturing when and where it is needed with significantly shorter lead times. As part of the Pharmacy on Demand (PoD) initiative, we demonstrate the potential for end-to-end manufacturing of multiple drug substances in reconfigurable devices, under common industrial constraints, and within a challenging manufacturing time frame. A new set of refrigerator-sized modules was constructed for the synthesis, isolation, and formulation of several drugs, with focus on achieving high manufacturing throughputs, and allowing for the production of pharmaceutical tablets. Their operation is demonstrated with the synthesis and formulation of USP-compliant tablets of diazepam, diphenhydramine hydrochloride, and ciprofloxacin hydrochloride, as well as liquid formulations of lidocaine hydrochloride and atropine sulfate.