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Annual Review of Chemical and Biomolecular Engineering

Volume 9, 2018

Continuous Manufacturing in Pharmaceutical Process Development and Manufacturing

Abstract

The pharmaceutical industry has found new applications for the use of continuous processing for the manufacture of new therapies currently in development. The transformation has been encouraged by regulatory bodies as well as driven by cost reduction, decreased development cycles, access to new chemistries not practical in batch, improved safety, flexible manufacturing platforms, and improved product quality assurance. The transformation from batch to continuous manufacturing processing is the focus of this review. The review is limited to small, chemically synthesized organic molecules and encompasses the manufacture of both active pharmaceutical ingredients (APIs) and the subsequent drug product. Continuous drug product is currently used in approved processes. A few examples of production of APIs under current good manufacturing practice conditions using continuous processing steps have been published in the past five years, but they are lagging behind continuous drug product with respect to regulatory filings.

Keyword(s): continuous manufacture, drug product, drug substance, pharmaceuticals
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2018-06-07
2024-04-16
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Literature Cited

  1. 1.  DiMasi JA, Grabowski HG, Hansen RW 2016. Innovation in the pharmaceutical industry: new estimates of R&D costs. J. Health Econ. 47:20–33
     [Google Scholar]
  2. 2.  Price WN II 2014. Making do in making drugs: innovation policy and pharmaceutical manufacturing. Boston Coll. Law Rev. 55:491
     [Google Scholar]
  3. 3.  Munos B 2009. Lessons from 60 years of pharmaceutical innovation. Nat. Rev. Drug Discov. 8:959–68
     [Google Scholar]
  4. 4.  Collins PC 2017. Development and implementation of continuous manufacturing processes for API Presented at 3rd FDA/PQRI Conf Adv. Prod. Qual Rockville, MD:
  5. 5.  Food Drug Adm 2004. PAT—a framework for innovative pharmaceutical development, manufacturing, and quality assurance Guid. Ind., Food Drug Adm Silver Spring, MD: https://www.fda.gov/downloads/drugs/guidances/ucm070305.pdf
  6. 6.  Food Drug Adm 2004. Pharmaceutical cGMPs for the 21st Century—A Risk-Based Approach Silver Spring, MD: Food Drug Adm.
  7. 7.  Lee SL, O'Connor TF, Yang X, Cruz CN, Chatterjee S et al. 2015. Modernizing pharmaceutical manufacturing: from batch to continuous production. J. Pharm. Innov. 10:191–99
     [Google Scholar]
  8. 8.  Cole KP, Campbell BM, Forst MB, McClary Groh J, Hess M et al. 2016. An automated intermittent flow approach to continuous Suzuki coupling. Org. Process Res. Dev. 20:820–30
     [Google Scholar]
  9. 9.  Kopach ME, Cole KP, Pollock PM, Johnson MD, Braden TM et al. 2016. Flow Grignard and lithiation: screening tools and development of continuous processes for a benzyl alcohol starting material. Org. Process Res. Dev. 20:1581–92
     [Google Scholar]
  10. 10.  Poechlauer P, Colberg J, Fisher E, Jansen M, Johnson MD et al. 2013. Pharmaceutical roundtable study demonstrates the value of continuous manufacturing in the design of greener processes. Org. Process Res. Dev. 17:1472–78
     [Google Scholar]
  11. 11.  Nasr MM, Krumme M, Matsuda Y, Trout BL, Badman C et al. 2017. Regulatory perspectives on continuous pharmaceutical manufacturing: moving from theory to practice: September 26–27, 2016, International Symposium on the Continuous Manufacturing of Pharmaceuticals. J. Pharm. Sci. 106:3199–206
     [Google Scholar]
  12. 12.  Almaya A, De Belder L, Meyer R, Nagapudi K, Lin HH et al. 2017. Control strategies for drug product continuous direct compression—state of control, product collection strategies, and startup/shutdown operations for the production of clinical trial materials and commercial products. J. Pharm. Sci. 106:930–43
     [Google Scholar]
  13. 13.  Aksu B, De Beer T, Folestad S, Ketolainen J, Linden H et al. 2012. Strategic funding priorities in the pharmaceutical sciences allied to Quality by Design (QbD) and Process Analytical Technology (PAT). Eur. J. Pharm. Sci. 47:402–5
     [Google Scholar]
  14. 14.  Rantanen J, Khinast J 2015. The future of pharmaceutical manufacturing sciences. J. Pharm. Sci. 104:3612–38
     [Google Scholar]
  15. 15.  Fisher AC, Lee SL, Harris DP, Buhse L, Kozlowski S et al. 2016. Advancing pharmaceutical quality: an overview of science and research in the U.S. FDA's Office of Pharmaceutical Quality. Int. J. Pharm. 515:390–402
     [Google Scholar]
  16. 16.  Tsukanov SV, Johnson MD, May SA, Rosemeyer M, Watkins MA et al. 2016. Development of an intermittent-flow enantioselective Aza-Henry reaction using an arylnitromethane and homogeneous Brønsted acid-base catalyst with recycle. Org. Process Res. Dev. 20:215–26
     [Google Scholar]
  17. 17.  Li J, Trout BL, Myerson AS 2016. Multistage continuous mixed-suspension, mixed-product removal (MSMPR) crystallization with solids recycle. Org. Process Res. Dev. 20:510–16
     [Google Scholar]
  18. 18.  Seifert T, Sievers S, Bramsiepe C, Schembecker G 2012. Small scale, modular and continuous: a new approach in plant design. Chem. Eng. Process. Process Intensif. 52:140–50
     [Google Scholar]
  19. 19. The Irish Times. 2016. Eli Lilly to invest €35m in Kinsale plant. The Irish Times April 5. https://www.irishtimes.com/business/health-pharma/eli-lilly-to-invest-35m-in-kinsale-plant-1.2598781
  20. 20. ISPE. 2017. 2017 ISPE Facility of the Year award winners announced. ISPE Newsletter Feb. 6. https://www.ispe.org/news/2017-facility-year-category-winners
  21. 21.  Congdon K 2015. Inside Pfizer's modular manufacturing PODs. Pharmaceutical Online https://www.pharmaceuticalonline.com/doc/inside-pfizer-s-modular-manufacturing-pods-0001
  22. 22.  Garguilo L 2017. Novartis and the arrival of the continuous manufacturing facility. Outsourced Pharma Feb. 8. https://www.outsourcedpharma.com/doc/novartis-and-the-arrival-of-the-continuous-manufacturing-facility-0001
  23. 23.  Stanton D 2016. J&J success will spur pharma's shift to continuous manufacturing, Rutgers. in-PharmaTechnologist.com April 20. http://www.in-pharmatechnologist.com/Processing/J-J-success-will-spur-shift-to-continuous-manufacturing-Rutgers
  24. 24.  MacDonald G 2016. Janssen working on other continuous processes post US FDA OK for Prezista. in-PharmaTechnologist.com April 12. http://www.in-pharmatechnologist.com/Processing/Janssen-working-on-other-continuous-processes-post-US-FDA-OK-for-Prezista
  25. 25.  Palmer E 2015. Vertex, J&J, GSK, Novartis all working on continuous manufacturing facilities. FiercePharma Feb. 9. http://www.fiercepharma.com/supply-chain/vertex-j-j-gsk-novartis-all-working-on-continuous-manufacturing-facilities
  26. 26.  Taylor P 2015. GSK and Pfizer team up on continuous manufacturing project. in-PharmaTechnologist.com Nov. 3. http://www.in-pharmatechnologist.com/Processing/GSK-and-Pfizer-team-up-on-continuous-manufacturing-project
  27. 27.  Plutschack MB, Pieber B, Gilmore K, Seeberger PH 2017. The hitchhiker's guide to flow chemistry. Chem. Rev. 117:11796–893
     [Google Scholar]
  28. 28.  Allison G, Cain YT, Cooney C, Garcia T, Bizjak TG et al. 2015. Regulatory and quality considerations for continuous manufacturing. May 20–21, 2014 Continuous Manufacturing Symposium. J. Pharm. Sci. 104:803–12
     [Google Scholar]
  29. 29.  Badman C, Trout BL 2015. Achieving continuous manufacturing. May 20–21, 2014 Continuous Manufacturing Symposium. J. Pharm. Sci. 104:779–80
     [Google Scholar]
  30. 30.  Baxendale IR, Braatz RD, Hodnett BK, Jensen KF, Johnson MD et al. 2015. Achieving continuous manufacturing: technologies and approaches for synthesis, workup, and isolation of drug substance. May 20–21, 2014 Continuous Manufacturing Symposium. J. Pharm. Sci. 104:781–91
     [Google Scholar]
  31. 31.  Byrn S, Futran M, Thomas H, Jayjock E, Maron N et al. 2015. Achieving continuous manufacturing for final dosage formation: challenges and how to meet them. May 20–21, 2014 Continuous Manufacturing Symposium. J. Pharm. Sci. 104:792–802
     [Google Scholar]
  32. 32.  Konstantinov KB, Cooney CL 2015. White paper on continuous bioprocessing. May 20–21, 2014 Continuous Manufacturing Symposium. J. Pharm. Sci. 104:813–20
     [Google Scholar]
  33. 33.  Myerson AS, Krumme M, Nasr M, Thomas H, Braatz RD 2015. Control systems engineering in continuous pharmaceutical manufacturing. May 20–21, 2014 Continuous Manufacturing Symposium. J. Pharm. Sci. 104:832–39
     [Google Scholar]
  34. 34.  Nepveux K, Sherlock J-P, Futran M, Thien M, Krumme M 2015. How development and manufacturing will need to be structured—heads of development/manufacturing. May 20–21, 2014 Continuous Manufacturing Symposium. J. Pharm. Sci. 104:850–64
     [Google Scholar]
  35. 35.  Page T, Dubina H, Fillipi G, Guidat R, Patnaik S et al. 2015. Equipment and analytical companies meeting continuous challenges. May 20–21, 2014 Continuous Manufacturing Symposium. J. Pharm. Sci. 104:821–31
     [Google Scholar]
  36. 36.  Srai JS, Badman C, Krumme M, Futran M, Johnston C 2015. Future supply chains enabled by continuous processing—opportunities and challenges. May 20–21, 2014 Continuous Manufacturing Symposium. J. Pharm. Sci. 104:840–49
     [Google Scholar]
  37. 37.  Welch C, Faul MM, Tummala S, Papageorgiou CD, Hicks F et al. 2017. The Enabling Technologies Consortium (ETC): fostering precompetitive collaborations on new enabling technologies for pharmaceutical research and development. Org. Process Res. Dev. 21:3414–19
     [Google Scholar]
  38. 38.  Lakerveld R, Benyahia B, Braatz RD, Barton PI 2013. Model-based design of a plant-wide control strategy for a continuous pharmaceutical plant. AIChE J 59:3671–85
     [Google Scholar]
  39. 39.  Lakerveld R, Benyahia B, Heider PL, Zhang H, Wolfe A et al. 2015. The application of an automated control strategy for an integrated continuous pharmaceutical pilot plant. Org. Process Res. Dev. 19:1088–100
     [Google Scholar]
  40. 40.  Jensen KF 2017. Flow chemistry—microreaction technology comes of age. AIChE J 63:858–69
     [Google Scholar]
  41. 41.  Gutmann B, Cantillo D, Kappe CO 2015. Continuous-flow technology—a tool for the safe manufacturing of active pharmaceutical ingredients. Angew. Chem. Int. Ed. 54:6688–728
     [Google Scholar]
  42. 42.  Wang T, Lu H, Wang J, Xiao Y, Zhou Y et al. 2017. Recent progress of continuous crystallization. J. Ind. Eng. Chem. 54:14–29
     [Google Scholar]
  43. 43.  Zhang D, Xu S, Du S, Wang J, Gong J 2017. Progress of pharmaceutical continuous crystallization. Engineering 3:354–64
     [Google Scholar]
  44. 44.  Jacoby R, Pernenkil L, Harutunian S, Heim M, Sabad ADeloitte 2015. Advanced Biopharmaceutical Manufacturing: An Evolution Underway New York: Deloitte https://www2.deloitte.com/content/dam/Deloitte/us/Documents/life-sciences-health-care/us-lshc-advanced-biopharmaceutical-manufacturing-white-paper-051515.pdf
  45. 45.  O'Brien M 2016. Powders to tablets in minutes: implementation of a portable, continuous, miniature, and modular (PCMM) factory in a warehouse Presented at FDA-AIChE Workshop Adopt Contin. Manuf Bethesda, MD:
  46. 46.  Madurawe R 2016. Continuous manufacturing: achieving the vision of modernizing pharmaceutical manufacturing Presented at FDA-AIChE Workshop Adopt Contin. Manuf. Bethesda, MD:
  47. 47.  McManus E 2016. Design and implementation of a small footprint continuous API facility for portfolio commercialization Presented at FDA-AIChE Workshop Adopt Contin. Manuf Bethesda, MD:
  48. 48.  Tsubogo T, Oyamada H, Kobayashi S 2015. Multistep continuous-flow synthesis of (R)- and (S)-rolipram using heterogeneous catalysts. Nature 520:329–32
     [Google Scholar]
  49. 49.  Lau SH, Galvan A, Merchant RR, Battilocchio C, Souto JA et al. 2015. Machines versus malaria: a flow-based preparation of the drug candidate OZ439. Org. Lett. 17:3218–21
     [Google Scholar]
  50. 50.  Ingham RJ, Battilocchio C, Fitzpatrick DE, Sliwinski E, Hawkins JM, Ley SV 2015. A systems approach towards an intelligent and self-controlling platform for integrated continuous reaction sequences. Angew. Chem. Int. Ed. 54:144–48
     [Google Scholar]
  51. 51.  Viviano M, Glasnov TN, Reichart B, Tekautz G, Kappe CO 2011. A scalable two-step continuous flow synthesis of nabumetone and related 4-aryl-2-butanones. Org. Process Res. Dev. 15:858–70
     [Google Scholar]
  52. 52.  Ghislieri D, Gilmore K, Seeberger PH 2015. Chemical assembly systems: layered control for divergent, continuous, multistep syntheses of active pharmaceutical ingredients. Angew. Chem. Int. Ed. 54:678–82
     [Google Scholar]
  53. 53.  Hopkin MD, Baxendale IR, Ley SV 2010. A flow-based synthesis of imatinib: the API of Gleevec. Chem. Commun. 46:2450–52
     [Google Scholar]
  54. 54.  Hopkin MD, Baxendale IR, Ley SV 2013. An expeditious synthesis of imatinib and analogues utilising flow chemistry methods. Org. Biomol. Chem. 11:1822–39
     [Google Scholar]
  55. 55.  Correia CA, Gilmore K, McQuade DT, Seeberger PH 2015. A concise flow synthesis of efavirenz. Angew. Chem. Int. Ed. 54:4945–48
     [Google Scholar]
  56. 56.  Murray PRD, Browne DL, Pastre JC, Butters C, Guthrie D, Ley SV 2013. Continuous flow-processing of organometallic reagents using an advanced peristaltic pumping system and the telescoped flow synthesis of (E/Z)-tamoxifen. Org. Process Res. Dev. 17:1192–208
     [Google Scholar]
  57. 57.  Cantillo D, Damm M, Dallinger D, Bauser M, Berger M, Kappe CO 2014. Sequential nitration/hydrogenation protocol for the synthesis of triaminophloroglucinol: safe generation and use of an explosive intermediate under continuous-flow conditions. Org. Process Res. Dev. 18:1360–66
     [Google Scholar]
  58. 58.  Elliott LD, Berry M, Harji B, Klauber D, Leonard J, Booker-Milburn KI 2016. A small-footprint, high-capacity flow reactor for UV photochemical synthesis on the kilogram scale. Org. Process Res. Dev. 20:1806–11
     [Google Scholar]
  59. 59.  Levesque F, Seeberger PH 2012. Continuous-flow synthesis of the anti-malaria drug artemisinin. Angew. Chem. Int. Ed. 51:1706–9
     [Google Scholar]
  60. 60.  Bodmann K, Marti R 2015. 12. Freiburger Symposium 2015: smart solutions in the chemical process & product development—case studies from the chemical industry. Chimia 69:698–707
     [Google Scholar]
  61. 61.  Cole KP, Groh JM, Johnson MD, Burcham CL, Campbell BM et al. 2017. Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow CGMP conditions. Science 356:1144–50
     [Google Scholar]
  62. 62.  May SA, Johnson MD, Braden TM, Calvin JR, Haeberle BD et al. 2012. Rapid development and scale-up of a 1H-4-substituted imidazole intermediate enabled by chemistry in continuous plug flow reactors. Org. Process Res. Dev. 16:982–1002
     [Google Scholar]
  63. 63.  Frederick MO, Calvin JR, Cope RF, LeTourneau ME, Lorenz KT et al. 2015. Development of an NH4Cl-catalyzed ethoxy ethyl deprotection in flow for the synthesis of merestinib. Org. Process Res. Dev. 19:1411–17
     [Google Scholar]
  64. 64.  May SA, Johnson MD, Buser JY, Campbell AN, Frank SA et al. 2016. Development and manufacturing GMP scale-up of a continuous Ir-catalyzed homogeneous reductive amination reaction. Org. Process Res. Dev. 20:1870–98
     [Google Scholar]
  65. 65.  Peer M, Weeranoppanant N, Adamo A, Zhang Y, Jensen KF 2016. Biphasic catalytic hydrogen peroxide oxidation of alcohols in flow: scale-up and extraction. Org. Process Res. Dev. 20:1677–85
     [Google Scholar]
  66. 66.  O'Neal EJ, Lee CH, Brathwaite J, Jensen KF 2015. Continuous nanofiltration and recycle of an asymmetric ketone hydrogenation catalyst. ACS Catal 5:2615–22
     [Google Scholar]
  67. 67.  Cui X, Mannan MS, Wilhite BA 2017. Segregated-feed membrane reactor design for alkylpyridine N-oxidation: implications for process safety and intensification. Ind. Eng. Chem. Res. 56:3822–32
     [Google Scholar]
  68. 68.  Levenspiel O 1998. Chemical Reaction Engineering Hoboken, NJ: Wiley, 3rd ed..
  69. 69.  White TD, Alt CA, Cole KP, Groh JM, Johnson MD, Miller RD 2014. How to convert a walk-in hood into a manufacturing facility: demonstration of a continuous, high-temperature cyclization to process solids in flow. Org. Process Res. Dev. 18:1482–91
     [Google Scholar]
  70. 70.  Cole KP, Johnson MD, Laurila ME, Stout JR 2017. An automated repeating batch with catalyst recycle approach to nitro group hydrogenolysis. React. Chem. Eng. 2:288–94
     [Google Scholar]
  71. 71.  Adamo A, Beingessner RL, Behnam M, Chen J, Jamison TF et al. 2016. On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system. Science 352:61–67
     [Google Scholar]
  72. 72.  Snead DR, Jamison TF 2015. A three-minute synthesis and purification of ibuprofen: pushing the limits of continuous-flow processing. Angew. Chem. Int. Ed. 54:983–87
     [Google Scholar]
  73. 73.  Lieberman HA 1990. Pharmaceutical Dosage Forms: Tablets, Vol. 2: Second Edition, Revised and Expanded Abingdon, UK: Taylor & Francis
     [Google Scholar]
  74. 74.  Lachman L, Lieberman HA, Kang JL 1976. The Theory and Practice of Industrial Pharmacy Philadelphia: Lea & Febiger, 2nd ed..
  75. 75.  Vervaet C, Remon JP 2005. Continuous granulation in the pharmaceutical industry. Chem. Eng. Sci. 60:3949–57
     [Google Scholar]
  76. 76. Am. Pharm. Rev. 2017. Pharmaceutical Tablet Press Machine/Rotary Tablet Press Fishers, IN: Am. Pharm. Rev http://www.americanpharmaceuticalreview.com/25310-Pharmaceutical-Manufacturing/25344-Pharmaceutical-Tablet-Press-Machine-Rotary-Tablet-Press/
  77. 77. Manufacturing Chemist Pharma. 2017. FEC40 Capsule Filling Machine can produce up to 400,000 capsules/hour. Manufacturing Chemist Pharma Jan. 30. https://www.manufacturingchemist.com/news/article_page/FEC40_Capsule_Filling_Machine_can_produce_up_to_400000_capsuleshour/125304
  78. 78.  Schaber SD, Gerogiorgis DI, Ramachandran R, Evans JMB, Barton PI, Trout BL 2011. Economic analysis of integrated continuous and batch pharmaceutical manufacturing: a case study. Ind. Eng. Chem. Res. 50:10083–92
     [Google Scholar]
  79. 79.  Pernenkil L, Cooney CL 2006. A review on the continuous blending of powders. Chem. Eng. Sci. 61:720–42
     [Google Scholar]
  80. 80.  Suresh P, Sreedhar I, Vaidhiswaran R, Venugopal A 2017. A comprehensive review on process and engineering aspects of pharmaceutical wet granulation. Chem. Eng. J. 328:785–815
     [Google Scholar]
  81. 81.  Beer P, Wilson D, Huang Z, De Matas M 2014. Transfer from high-shear batch to continuous twin screw wet granulation: a case study in understanding the relationship between process parameters and product quality attributes. J. Pharm. Sci. 103:3075–82
     [Google Scholar]
  82. 82.  Jorgensen A, Rantanen J, Karjalainen M, Khriachtchev L, Rasanen E, Yliruusi J 2002. Hydrate formation during wet granulation studied by spectroscopic methods and multivariate analysis. Pharm. Res. 19:1285–91
     [Google Scholar]
  83. 83.  Leuenberger H 2001. New trends in the production of pharmaceutical granules: batch versus continuous processing. Eur. J. Pharm. Biopharm. 52:289–96
     [Google Scholar]
  84. 84.  Werani J, Gruenberg M, Ober C, Leuenberger H 2004. Semicontinuous granulation—the process of choice for the production of pharmaceutical granules?. Powder Technol 140:163–68
     [Google Scholar]
  85. 85.  Loh ZH, Er DZ, Chan LW, Liew CV, Heng PW 2011. Spray granulation for drug formulation. Expert Opin. Drug Deliv. 8:1645–61
     [Google Scholar]
  86. 86.  Glatt Technol Innovative Technologies for Granules and Pellets Moscow: Glatt Technol https://www.glatt.com/fileadmin/user_upload/content/pdf_downloads/AB_innovative_technologies_en_111017.pdf
  87. 87.  Seem TC, Rowson NA, Ingram A, Huang Z, Yu S et al. 2015. Twin screw granulation—a literature review. Powder Technol 276:89–102
     [Google Scholar]
  88. 88.  Vercruysse J, Córdoba Díaz D, Peeters E, Fonteyne M, Delaet U et al. 2012. Continuous twin screw granulation: influence of process variables on granule and tablet quality. Eur. J. Pharm. Biopharm. 82:205–11
     [Google Scholar]
  89. 89.  Djuric D, Kleinebudde P 2010. Continuous granulation with a twin-screw extruder: impact of material throughput. Pharm. Dev. Technol. 15:518–25
     [Google Scholar]
  90. 90.  Kumar A, Dhondt J, Vercruysse J, De Leersnyder F, Vanhoorne V et al. 2016. Development of a process map: a step towards a regime map for steady-state high shear wet twin screw granulation. Powder Technol 300:73–82
     [Google Scholar]
  91. 91.  Hapgood KP, Litster JD, Smith R 2003. Nucleation regime map for liquid bound granules. AIChE J 49:350–61
     [Google Scholar]
  92. 92.  Iveson SM, Litster JD 1998. Growth regime map for liquid-bound granules. AIChE J 44:1510–18
     [Google Scholar]
  93. 93.  Barrasso D, Walia S, Ramachandran R 2013. Multi-component population balance modeling of continuous granulation processes: a parametric study and comparison with experimental trends. Powder Technol 241:85–97
     [Google Scholar]
  94. 94.  Iveson SM 2002. Limitations of one-dimensional population balance models of wet granulation processes. Powder Technol 124:219–29
     [Google Scholar]
  95. 95.  Chaturbedi A, Bandi CK, Reddy D, Pandey P, Narang A et al. 2017. Compartment based population balance model development of a high shear wet granulation process via dry and wet binder addition. Chem. Eng. Res. Des. 123:187–200
     [Google Scholar]
  96. 96.  Vercruysse J, Burggraeve A, Fonteyne M, Cappuyns P, Delaet U et al. 2015. Impact of screw configuration on the particle size distribution of granules produced by twin screw granulation. Int. J. Pharm. 479:171–80
     [Google Scholar]
  97. 97.  Fonteyne M, Wickstrom H, Peeters E, Vercruysse J, Ehlers H et al. 2014. Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets. Eur. J. Pharm. Biopharm. 87:252–63
     [Google Scholar]
  98. 98.  Fonteyne M, Vercruysse J, Díaz DC, Gildemyn D, Vervaet C et al. 2013. Real-time assessment of critical quality attributes of a continuous granulation process. Pharm. Dev. Technol. 18:85–97
     [Google Scholar]
  99. 99.  Food Drug Adm 2015. FDA approves new treatment for cystic fibrosis News Release, July 2
  100. 100.  Yu L 2016. Continuous manufacturing has a strong impact on drug quality. FDA Voice April 12. https://blogs.fda.gov/fdavoice/index.php/2016/04/continuous-manufacturing-has-a-strong-impact-on-drug-quality/
  101. 101.  Swinney KA 2016. Drug product continuous manufacturing: from business case to commercial manufacturing Presented at 2nd Int. Symp. Contin Manuf. Pharm. Implement. Technol. Regul Cambridge, MA:
  102. 102.  Kleinebudde P 2004. Roll compaction/dry granulation: pharmaceutical applications. Eur. J. Pharm. Biopharm. 58:317–26
     [Google Scholar]
  103. 103.  Acevedo D, Muliadi A, Giridhar A, Litster JD, Romanach RJ 2012. Evaluation of three approaches for real-time monitoring of roller compaction with near-infrared spectroscopy. AAPS PharmSciTech 13:1005–12
     [Google Scholar]
  104. 104.  Zhang J, Pei C, Schiano S, Heaps D, Wu CY 2016. The application of terahertz pulsed imaging in characterising density distribution of roll-compacted ribbons. Eur. J. Pharm. Biopharm. 106:20–25
     [Google Scholar]
  105. 105.  Mangal H, Kirsolak M, Kleinebudde P 2016. Roll compaction/dry granulation: suitability of different binders. Int. J. Pharm. 503:213–19
     [Google Scholar]
  106. 106.  Kushner J IV, Langdon BA, Hiller JI, Carlson GT 2011. Examining the impact of excipient material property variation on drug product quality attributes: a quality-by-design study for a roller compacted, immediate release tablet. J. Pharm. Sci. 100:2222–39
     [Google Scholar]
  107. 107.  Shi Z, McGhehey KC, Leavesley IM, Manley LF 2016. On-line monitoring of blend uniformity in continuous drug product manufacturing process—the impact of powder flow rate and the choice of spectrometer: dispersive vs. FT. J. Pharm. Biomed. Anal. 118:259–66
     [Google Scholar]
  108. 108.  Laske S, Paudel A, Scheibelhofer O 2017. A review of PAT strategies in secondary solid oral dosage manufacturing of small molecules. J. Pharm. Sci. 106:667–712
     [Google Scholar]
  109. 109.  Hertrampf A, Müller H, Menezes JC, Herdling T 2015. A PAT-based qualification of pharmaceutical excipients produced by batch or continuous processing. J. Pharm. Biomed. Anal. 114:208–15
     [Google Scholar]
  110. 110.  Vanarase AU, Järvinen M, Paaso J, Muzzio FJ 2013. Development of a methodology to estimate error in the on-line measurements of blend uniformity in a continuous powder mixing process. Powder Technol 241:263–71
     [Google Scholar]
  111. 111.  Osorio JG, Stuessy G, Kemeny GJ, Muzzio FJ 2014. Characterization of pharmaceutical powder blends using in situ near-infrared chemical imaging. Chem. Eng. Sci. 108:244–57
     [Google Scholar]
  112. 112.  Mateo-Ortiz D, Colon Y, Romañach RJ, Méndez R 2014. Analysis of powder phenomena inside a Fette 3090 feed frame using in-line NIR spectroscopy. J. Pharm. Biomed. Anal. 100:40–49
     [Google Scholar]
  113. 113.  Gladd T 2016. Merck's path to continuous manufacturing for solid oral dose products: What stands in the way?. Life Science Leader Dec. 8. https://www.lifescienceleader.com/doc/merck-s-path-to-continuous-manufacturing-for-solid-oral-dose-products-what-stands-in-the-way-0001
  114. 114.  Roth WJ, Almaya A, Kramer TT, Hofer JD 2017. A demonstration of mixing robustness in a direct compression continuous manufacturing process. J. Pharm. Sci. 106:1339–46
     [Google Scholar]
  115. 115.  Lakio S, Tajarobi P, Wikström H, Fransson M, Arnehed J et al. 2016. Achieving a robust drug release from extended release tablets using an integrated continuous mixing and direct compression line. Int. J. Pharm. 511:659–68
     [Google Scholar]
  116. 116.  Belder LD 2016. Business Case Drivers and Deployment Strategies in the Current Landscape for Continuous Drug Product Manufacturing Presented at 2nd Int. Symp. Contin Manuf. Pharm. Implement. Technol. Regul Cambridge, MA:
  117. 117.  Gonnissen Y, Gonçalves SI, De Geest BG, Remon JP, Vervaet C 2008. Process design applied to optimise a directly compressible powder produced via a continuous manufacturing process. Eur. J. Pharm. Biopharm. 68:760–70
     [Google Scholar]
  118. 118.  Gonnissen Y, Gonçalves SI, Remon JP, Vervaet C 2008. Mixture design applied to optimize a directly compressible powder produced via cospray drying. Drug Dev. Ind. Pharm. 34:248–57
     [Google Scholar]
  119. 119.  Gonnissen Y, Remon JP, Vervaet C 2007. Development of directly compressible powders via co-spray drying. Eur. J. Pharm. Biopharm. 67:220–26
     [Google Scholar]
  120. 120.  Gonnissen Y, Remon JP, Vervaet C 2008. Effect of maltodextrin and superdisintegrant in directly compressible powder mixtures prepared via co-spray drying. Eur. J. Pharm. Biopharm. 68:277–82
     [Google Scholar]
  121. 121.  Hancock BC, Zografi G 1997. Characteristics and significance of the amorphous state in pharmaceutical systems. J. Pharm. Sci. 86:1–12
     [Google Scholar]
  122. 122.  Hitzer P, Bauerle T, Drieschner T, Ostertag E, Paulsen K et al. 2017. Process analytical techniques for hot-melt extrusion and their application to amorphous solid dispersions. Anal. Bioanal. Chem. 409:4321–33
     [Google Scholar]
  123. 123.  Treffer D, Wahl P, Markl D, Koscher G, Roblegg E, Khinast JG 2013. Hot melt extrusion as a continuous pharmaceutical manufacturing process. Melt Extrusion: Materials, Technology and Drug Product Design MA Repka, N Langley, J DiNunzio 363–96 New York: Springer
     [Google Scholar]
  124. 124.  Grymonpre W, Verstraete G, Van Bockstal PJ, Van Renterghem J, Rombouts P et al. 2017. In-line monitoring of compaction properties on a rotary tablet press during tablet manufacturing of hot-melt extruded amorphous solid dispersions. Int. J. Pharm. 517:348–58
     [Google Scholar]
  125. 125.  Clarke A, Doughty D, Khinast J, Rantanen J 2017. Development of liquid dispensing technology for the manufacture of low dose drug products. Continuous Manufacturing of Pharmaceuticals P Kleinebudde, J Khinast, J Rantanen 551–75 Hoboken, NJ: John Wiley & Sons
     [Google Scholar]
  126. 126.  Clarke A, Phillips D Liquid Dispensing Technology (LDT) Brentford, UK: GSK https://www.gsk.com/media/2758/liquid-dispensing-technology-leaflet.pdf
  127. 127.  Euliss LE, DuPont JA, Gratton S, DeSimone J 2006. Imparting size, shape, and composition control of materials for nanomedicine. Chem. Soc. Rev. 35:1095–104
     [Google Scholar]
  128. 128.  Petros RA, Ropp PA, DeSimone JM 2008. Reductively labile PRINT particles for the delivery of doxorubicin to HeLa cells. J. Am. Chem. Soc. 130:5008–9
     [Google Scholar]
  129. 129.  Parrott MC, Finniss M, Luft JC, Pandya A, Gullapalli A et al. 2012. Incorporation and controlled release of silyl ether prodrugs from PRINT nanoparticles. J. Am. Chem. Soc. 134:7978–82
     [Google Scholar]
  130. 130.  Mascia S, Heider PL, Zhang H, Lakerveld R, Benyahia B et al. 2013. End-to-end continuous manufacturing of pharmaceuticals: integrated synthesis, purification, and final dosage formation. Angew. Chem. Int. Ed. 52:12359–63
     [Google Scholar]
  131. 131.  O'Connor T 2016. How process models can facilitate quality risk management for emerging technologies Presented at FDA-AIChE Workshop Adopt Cont. Manuf Bethesda, MD:
  132. 132.  Rockoff JD 2015. Drug making breaks away from its old ways: “Continuous-manufacturing” process can improve quality control, speed output. Wall Street Journal Feb. 8
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Continuous Manufacturing in Pharmaceutical Process Development and Manufacturing
Annual Review of Chemical and Biomolecular Engineering 9, 253 (2018); https://doi.org/10.1146/annurev-chembioeng-060817-084355
/content/journals/10.1146/annurev-chembioeng-060817-084355
/content/journals/10.1146/annurev-chembioeng-060817-084355
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