Process Development and Case Studies of Continuous Reactor Systems for Production of API and Pharmaceutical Intermediates

Chemical Engineering in the Pharmaceutical Industry: R&D to Manufacturing

Volumn , Issue , 2010, Pages 437-455

  Laporte, Thomas L ^a   Wang, Chenchi ^a   Jones, G Scott ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

Continuous deprotection reaction lab to Kilo lab scale up; Continuous reactor and ancillary systems considerations; Process development and continuous reactor system case studies production of API and pharmaceutical intermediates

Indexed keywords

EID: 84889464572     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470882221.ch23     Document Type: Chapter

References (31)

1. Higgins S. Are more fine specialty chemicals being moved into continuous process plants? CHIMICA OFFI/Chemistry Today, September 1998.
2. Pellek A,Van Arnum P. Continuous processing: moving with or against the manufacturing flow, PharmTech 2008;9(32): 52-58.
3. Bogaert-Alvarez RJ, Demena P, Kodersha G, Polomski RE, Soundararajan S,Wang SS. Continuous Processing to control a potentially hazardous process: conversion of aryl 1,1-dimethylpropargyl ethers to 2,2-dimethylchromens (2,2-dimethyl-2H-1-benzopyrans). Org. Process Res. Dev. 2001;5:636.
4. Panke G, Schwalbe T, Stirner W, Taghavi-Moghadam S, Wille G. A practical approach of continuous processing to high energetic nitration reactions in microreactors. Synthesis 2003; 18:2827.
5. Brechtelsbauer C, Ricard F. Reaction engineering evaluation and utilization of static mixer technology for the synthesis of pharmaceuticals. Org. Process Res. Dev. 2001;5:646.
6. Roberge DM, Bieler N, Thalmann M. Microreactor technology and continuous processes in the fine chemical and pharmaceutical industries. Fine Chem. 2006; 14.
7. LaPorte TL,Wang C. Continuous processes for the production of pharmaceutical intermediates and active pharmaceutical ingredients. Curr. Opin. Drug Discov. Dev. 2007;10(6): 738-745.
8. Thakur RK, Vial C, Nigam KDP, Nauman EB, Djelveh G. Static mixers in the process industries-a review. Trans IChemE 2003;81(A):787.
9. Stankiewicz A, Drinkenburg AAH. Process intensification: history, philosophy, principles. Chem. Ind. (Dekker) 2004; 98:1-32.
10. Ritter SK. A New Spin on Reactor Design-Refined Rotor-Stator System has the Potential to Boost Chemical Process Intensification Efforts, C&EN, July 29, 2002.
11. Brechtelsbauer C, Lewis N, Oxley P, Richard F. Evaluation of a spinning disc reactor for continuous processing. Org. Process Res. Dev. 2001;5:65-68.
12. Micronit Microfluidics BV. http://www.micronit.com, 2009.
13. EhrfeldW, Hessel V, Löwe H. Microreactors, New Technology for Modern Chemistry, 1st edition, Wiley-VCH, Weinheim 2000, Chapter 3.
14. Dapremont O, Zeagler L, DuBay W. Reducing costs through continuous processing. Sp2, June 22-24, 2007.
15. Reuters: AMPAC Fine Chemicals Announces the Inauguration of the New cGMP Continuous Processing Development Facility, March 9, 2009
16. Roberge DM, Ducry L, Bieler N, Cretton P, Zimmermann B. Microreactor technology: a revolution for the fine chemical and pharmaceutical industries? Chem. Eng. Technol. 2005;28(3): 318-323.
17. Günther M, Scheider S, Wagner J, Gorges R, Henkel T, Kielpinski M, Bierbaum R, Köhler JM. Characterisation of residence time and residence time distribution in chip reactors with modular arrangements by integrated optical detection. Chem. Eng. J. 2004;101:373-378.
18. LaPorte TL, Hamedi M, DePue JS, Shen L,Watson D, Hsieh D. Development and scale-up of three consecutive continuous reactions for production of 6-hydroxybuspirone. Org. Process Res. Dev. 2008;12:956-966.
19. Choe J, Kim Y, Song KH. Continuous synthesis of an intermediate of quinolone antibiotic drug using static mixers. Org. Process Res. Dev. 2003;7(2):187-190.
20. Schwalbe T, Kursawe A, Sommer J. Application report on operating cellular process chemistry plants in fine chemical and contract manufacturing industries. Chem. Eng. Technol. 2005; 28(4):408-419.
21. Thayer A. Handle with care. Chem. Eng. News 2009, March 16.
22. Lonza News Release: Lonza secures important manufacturing contract using its proprietary microreactor technology, May 26, 2009
23. US Food and Drug Administration, Center for Drug Evaluation and Research: Guidance for Industry PAT-A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance, September 2004
24. Lobbecke S, Ferstl W, Panic S, Turcke T. Concepts for modularization and automation of microreaction technology. Chem. Eng. Technol. 2005;28(4):484-493.
25. Ferstl W, Klahn T, Schweikert W, Billeb G, Schwarzer M, Loebbecke S. Inline analysis in microreaction technology: a suitable tool for process screening and optimization. Chem. Eng. Technol. 2007;30(3):370-378.
26. Charette A, Marcoux JF. Spectroscopic characterization of (iodomethyl)zinc reagents involved in stereoselective reactions: spectroscopic evidence that IZnCH2I is not An (CH2I)2 {thorn} ZnI2 in the presence of an ether. J. Am. Chem. Soc. 1996;118:4539-4549.
27. Davies S, Ling K, Roberts P, Russell A, Thomson J. Diastereoselective Simmons-Smith cyclopropanation of allylic amines and carbamates. Chem. Commun. 2007;4029-4031.
28. Pitts DR, Sissom LE. Heat Transfer, McGraw-Hill, 1977.
29. Mullin R. Cover story-breaking down barriers: drugmakers are paving the way to more streamlined manufacturing via culture change in R&D. Chem. Eng. News 2007;85(04): 11-17.
30. Berry M. After a Century of Batch Manufacturing API, What Does Continuous Processing Offer? PhRMA API Workshop, 2009.
31. ICH Harmonised Tripartite Guideline Q7: Good Manufacturing Practice Guideline for Active Pharmaceutical Ingredients, 2000