15.2 Flow Chemistry in the Pharmaceutical Industry: Part 2
Book
Editors: Jamison, T. F.; Koch, G.
Title: Flow Chemistry in Organic Synthesis
Print ISBN: 9783132423312; Online ISBN: 9783132423350; Book DOI: 10.1055/b-006-161272
1st edition © 2018. Thieme. All rights reserved.
Georg Thieme Verlag KG, Stuttgart
Subjects: Organic Chemistry;Chemical Reactions, Catalysis;Organometallic Chemistry;Laboratory Techniques, Stoichiometry
Science of Synthesis Reference Libraries
Parent publication
Title: Science of Synthesis
DOI: 10.1055/b-00000101
Series Editors: Fürstner, A. (Editor-in-Chief); Carreira, E. M.; Faul, M.; Kobayashi, S.; Koch, G.; Molander, G. A.; Nevado, C.; Trost, B. M.; You, S.-L.
Type: Multivolume Edition
Abstract
The development and application of continuous-flow drug-substance manufacturing at Eli Lilly is described. A series of examples are provided in which a continuous process was developed to solve problems associated with an existing batch process. The three distinct areas of focus are: facilitation of early phase delivery, hybrid batch/flow processes at manufacturing scale, and small-volume continuous manufacturing (linked multiunit operation processes at 10 kg/day throughput). An overview is provided of the types of reactors implemented in our program and the chemistries they enable. The use of online process analytical technology is also described for each of these systems. Special emphasis is placed on the examples pertaining to increased safety and improved product quality gained from flow processing.
Key words
continuous processing - flow technologies - process analytical technology - plug-flow reactors - continuous stirred-tank reactors - intermittent stirred tanks - small-volume continuous manufacturing - process development - continuous crystallization- 2 Lee SL, OʼConnor TF, Yang X, Cruz CN, Chatterjee S, Madurawe RD, Moore CMV, Yu LX, Woodcock J. J. Pharm. Innov. 2015; 10: 191
- 3 www.aiche.org/conferences/fda-aiche-workshop-on-adopting-continuous-manufacturing/2016/proceeding/group/general-program Proceeding: FDA-AIChE Workshop on Adopting Continuous Manufacturing, 29 Feb. 2016, Collins, P. C., Ed.; (Accessed August 2018).
- 4 Fischer E. www.pharmaceutical-technology.com/features/featuregoing-with-the-flow-continuous-manufacturing/ Going with the flow: continuous manufacturing, 22 Jan. 2012 (accessed August 2018).
- 5 Challener C. www.pharmtech.com/glaxosmithkline-adopts-continuous-manufacturing-preparation-key-intermediate GlaxoSmithKline Adopts Continuous Manufacturing for Preparation of Key Intermediate, 9 Oct. 2013 (Accessed August 2018).
- 6 Rincón JA, Barberis M, González-Esguevillas M, Johnson MD, Niemeier JK, Sun W.-M. Org. Process Res. Dev. 2011; 15: 1428
- 7 May SA, Johnson MD, Braden TM, Calvin JR, Haeberle BD, Jines AR, Miller RD, Plocharczyk EF, Rener GA, Richey RN, Schmid CR, Vaid RK, Yu H. Org. Process Res. Dev. 2012; 16: 982
- 8 White TD, Alt CA, Cole KP, McClary Groh J, Johnson MD, Miller RD. Org. Process Res. Dev. 2014; 18: 1482
- 9 Cole KP, Campbell BM, Forst MB, McClary Groh J, Hess M, Johnson MD, Miller RD, Mitchell D, Polster CS, Reizman BJ, Rosemeyer M. Org. Process Res. Dev. 2016; 20: 820
- 10 Tsukanov SV, Johnson MD, May SA, Rosemeyer M, Watkins MA, Kolis SP, Yates MH, Johnston JN. Org. Process Res. Dev. 2016; 20: 215
- 11 Slattery CN, Deasy RE, Maguire AR, Kopach ME, Singh UK, Argentine MD, Trankle WG, Scherer RB, Moynihan H. J. Org. Chem. 2013; 78: 5955
- 12 Kopach ME, Cole KP, Pollock PM, Johnson MD, Braden TM, Webster LP, McClary Groh J, McFarland AD, Schafer JP, Adler JJ, Rosemeyer M. Org. Process Res. Dev. 2016; 20: 1581
- 13 Osterberg PM, Niemeier JK, Welch CJ, Hawkins JM, Martinelli JR, Johnson TE, Root TW, Stahl SS. Org. Process Res. Dev. 2015; 19: 1537
- 14 May SA, Johnson MD, Buser JY, Campbell AN, Frank SA, Haeberle BD, Hoffman PC, Lambertus GR, McFarland AD, Moher ED, White TD, Hurley DD, Corrigan AP, Gowran O, Kerrigan NG, Kissane MG, Lynch RR, Sheehan P, Spencer RD, Pulley SR, Stout JR. Org. Process Res. Dev. 2016; 20: 1870
- 15 Johnson MD, May SA, Haeberle B, Lambertus GR, Pulley SR, Stout JR. Org. Process Res. Dev. 2016; 20: 1305
- 16 Johnson MD, May SA, Calvin JR, Lambertus GR, Kokitkar PB, Landis CR, Jones BR, Abrams ML, Stout JR. Org. Process Res. Dev. 2016; 20: 888
- 18 Frederick MO, Frank SA, Vicenzi JT, LeTourneau ME, Berglund KD, Edward AW, Alt CA. Org. Process Res. Dev. 2014; 18: 546
- 20 Frederick MO, Calvin JR, Cope RF, LeTourneau ME, Lorenz KT, Johnson MD, Maloney TD, Pu YJ, Miller RD, Cziesla LE. Org. Process Res. Dev. 2015; 19: 1411
- 21 Eli Lilly to invest €35m in Kinsale plant. 5. April 2016; Accessed August , 2018 at: www.irishtimes.com/business/health-pharma/eli-lilly-to-invest-35m-in-kinsale-plant-1.2598781
- 22 White TD, Berglund KD, McClary Groh J, Johnson MD, Miller RD, Yates MH. Org. Process Res. Dev. 2012; 16: 939
- 23 Johnson MD, May SA, Calvin JR, Remacle J, Stout JR, Diseroad WD, Zaborenko N, Haeberle BD, Sun W.-M, Miller MT, Brennan J. Org. Process Res. Dev. 2012; 16: 1017
- 24 Cole KP, McClary Groh J, Johnson MD, Burcham CL, Campbell BM, Diseroad WD, Heller MR, Howell JR, Kallman NJ, Koenig TM, May SA, Miller RD, Mitchell D, Myers DP, Myers SS, Phillips JL, Polster CS, White TD, Cashman J, Hurley D, Moylan R, Sheehan P, Spencer RD, Desmond K, Desmond P, Gowran O. Science (Washington, D. C.) 2017; 356: 1144