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.
Traditional
pharmaceutical manufacturing operates around a supply
chain that is subject to complex logistics and is vulnerable to spikes
in demand and interruptions. In this context, continuous pharmaceutical
manufacturing in portable, refrigerator-sized factories is a promising
solution with applications in battlefield medicine, pandemic response,
and mitigation of local medical emergencies. A new iteration of the
pharmacy on demand initiative is hereby presented, involving the development
of equipment and processes for the manufacture of ciprofloxacin HCl
with commercialization in mind. This article covers the implementation
and the feedback control strategies for downstream manufacturing,
as well as the results of the first end-to-end continuous manufacturing
campaign. The results involve a significant leap from prior iterations,
consistently attaining drug substance specifications in a fully automated
process and with a 4-fold increase in the process throughput over
the most recent iteration.
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