title: On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system.
abstract: Pharmaceutical manufacturing typically uses batch processing at multiple locations. Disadvantages of this approach include long production times and the potential for supply chain disruptions. As a preliminary demonstration of an alternative approach, we report here the continuous-flow synthesis and formulation of active pharmaceutical ingredients in a compact, reconfigurable manufacturing platform. Continuous end-to-end synthesis in the refrigerator-sized [1.0 meter (width) × 0.7 meter (length) × 1.8 meter (height)] system produces sufficient quantities per day to supply hundreds to thousands of oral or topical liquid doses of diphenhydramine hydrochloride, lidocaine hydrochloride, diazepam, and fluoxetine hydrochloride that meet U.S. Pharmacopeia standards. Underlying this flexible plug-and-play approach are substantial enabling advances in continuous-flow synthesis, complex multistep sequence telescoping, reaction engineering equipment, and real-time formulation.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Adamo
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Beingessner
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Behnam
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. tfj@mit.edu kfjensen@mit.edu myerson@mit.edu.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Jamison
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. tfj@mit.edu kfjensen@mit.edu myerson@mit.edu.
authors.forename: Klavs F
authors.initials: KF
authors.lastname: Jensen
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Jean-Christophe M
authors.initials: JC
authors.lastname: Monbaliu
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. tfj@mit.edu kfjensen@mit.edu myerson@mit.edu.
authors.forename: Allan S
authors.initials: AS
authors.lastname: Myerson
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Eve M
authors.initials: EM
authors.lastname: Revalor
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Snead
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Torsten
authors.initials: T
authors.lastname: Stelzer
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Nopphon
authors.initials: N
authors.lastname: Weeranoppanant
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Shin Yee
authors.initials: SY
authors.lastname: Wong
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003975:Diazepam / Q000138:chemical synthesis / Q000592:standards; D004155:Diphenhydramine / Q000138:chemical synthesis / Q000592:standards; D008012:Lidocaine / Q000138:chemical synthesis / Q000592:standards; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis* / Q000592:standards; D010602:Pharmacopoeias as Topic
chemical_list: D004364:Pharmaceutical Preparations; D004155:Diphenhydramine; D008012:Lidocaine; D003975:Diazepam