Flexible Manufacturing: The Future State of Drug Product Development and Commercialization in the Pharmaceutical Industry

  • Yash KapoorEmail author
  • Robert F. MeyerEmail author
  • Brian K. Meyer
  • James C. DiNunzio
  • Akhilesh Bhambhani
  • Justin Stanbro
  • Kristin J. M. Ploeger
  • Erin N. Guidry
  • Gregory M. Troup
  • Adam T. Procopio
  • Allen C. Templeton


Flexible manufacturing systems are needed in the pharmaceutical industry due to the future challenges of volatility, uncertainty, complexity, and ambiguity [1]. Compared to traditional manufacturing systems that dominate the pharmaceutical industry today, processes that are better able to react to changes in the types of products being sold, the volume of sales, and the facilities needed for production will be an asset to an organization. Many emerging technologies are inherently adaptable, though the types of flexibility exhibited vary widely. The nature of these emerging technologies is examined here, and the case is made that flexibility should be valued as much as cost and time when selecting technologies, even though flexible manufacturing systems require extra time and money initially. An outlook on this type of manufacturing is shared with the assertion that flexible development and manufacturing would help reduce overall cost and better serve patient needs following the initial investment period. In the next decade, concentrated effort is needed from industry, academia, suppliers, and regulators to enable more agile and nimble pharmaceutical development and manufacturing.


Flexibility PODS Robotics 3D printing Digital Continuous manufacturing 



We would like to thank Richard Osifchin, Jennifer Baxter, Ian McConnell, Cathy McFerran, and Heidi Ferguson in Preclinical Development and Joseph Kukura in Global Pharmaceutical Operations at Merck & Co., Inc., Kenilworth, NJ, USA, for their insightful comments and guidance.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Bennett N, Lemoine J. What VUCA really means for you. Harvard Business Review. 2014;92(1–2).Google Scholar
  2. 2.
    Hurter P, Thomas H, Nadig D, Emiabata-Smith D, Paone A. Implementing continuous manufacturing to streamline and accelerate drug development. AAPS Newsmag. 2013;16:15–9.Google Scholar
  3. 3.
  4. 4.
  5. 5. Accessed 06 Dec 2019.
  6. 6.
  7. 7.
  8. 8.
  9. 9.
    U.S. Pharmaceutical CGMPs for the 21st Century - A Risk-Based Approach. Maryland: Food and Drug Administration; 2004.Google Scholar
  10. 10.
    Yu LX, Amidon G, Khan MA, Hoag SW, Polli J, Raju GK, et al. Understanding pharmaceutical quality by design. AAPS J. 2014;16(4):771–84.CrossRefGoogle Scholar
  11. 11.
    Chryssolouris G. Flexibility and its measurement. CIRP Ann. 1996;45(2):581–7.CrossRefGoogle Scholar
  12. 12.
    Browne J, Dubois D, Rathmill K, Sethi SP, Stecke KE. Classification of flexible manufacturing systems. 1984. FEMS Mag. 1984;2(2):114–7.Google Scholar
  13. 13.
    Zidan A. CDER Researchers Explore the Promise and Potential of 3D Printed Pharmaceuticals. Spotlight on CDER Science: U.S. Food & Drug Administration; 2017.Google Scholar
  14. 14.
    Norman J, Madurawe RD, Moore CMV, Khan MA, Khairuzzaman A. A new chapter in pharmaceutical manufacturing: 3D-printed drug products. Adv Drug Deliv Rev. 2017;108:39–50.CrossRefGoogle Scholar
  15. 15.
    Smith D, Kapoor Y, Hermans A, Nofsinger R, Kesisoglou F, Gustafson TP, et al. 3D printed capsules for quantitative regional absorption studies in the GI tract. Int J Pharm. 2018;550(1–2):418–28.CrossRefGoogle Scholar
  16. 16.
    Liang K, Carmone S, Brambilla D, Leroux JC. 3D printing of a wearable personalized oral delivery device: a first in human study. Sci Adv. 2018;4(5):1–11.CrossRefGoogle Scholar
  17. 17.
    Jamroz W, Szafraniec J, Kurek M, Jachowicz R. 3D printing in pharmaceutical and medical applications – recent achievements and challenges. Pharm Res. 2018;35(9):176.CrossRefGoogle Scholar
  18. 18.
    Robotics in aseptic drug manufacturing. Staubli. Accessed 06 Dec 2019.
  19. 19.
    Baker H, Faia M. Containment, Multi-Product Facilities, & Robotics: Future of Aseptic Processing. iSpeak Blog: ISPE; 2019.Google Scholar
  20. 20.
    Lee SL, O’Connor TF, Yang X, Cruz CN, Chatterjee S, Madurawe RD, et al. Modernizing pharmaceutical manufacturing: from batch to continuous production. J Pharm Innov. 2015;10:191–9.CrossRefGoogle Scholar
  21. 21.
    Plumb K. Continuous processing in the pharmaceutical industry: changing the mind set. Chem Eng Res Des. 2005;83(6):730–8.CrossRefGoogle Scholar
  22. 22.
    Poechlauer P, Manley J, Broxterman R, Gregertsen B, Ridemark M. Continuous processing in the manufacture of active pharmaceutical ingredients and finished dosage forms: an industry perspective. Org Process Res Dev. 2012;16(10):1586–90.CrossRefGoogle Scholar
  23. 23.
    Fu J, Durance TD, Yaghmaee P, inventors; ENWAVE CORP, assignee. Microwave vacuum-drying of organic materials. USA patent 9958203. 2018.Google Scholar
  24. 24.
    Langford A, Bhatnagar B, Wlaters R, Tchessalov S, Ohtake S. Drying technologies for biopharmaceutical applications: recent developments and future direction. Dry Technol. 2018;36(6):677–84.CrossRefGoogle Scholar
  25. 25.
    Bhambhani A, Evans RK, Gupta P, Smith RL, Williams DM, inventors; Merck Sharp & Dohme Corp., assignee. Process for preparing formulations for gastrointestinal-targeted therapies. USA Patent Appl. No. 15/768,044. 2018.Google Scholar
  26. 26.
    Cleanroom Product Offerings, G-CON Manufacturing, Inc. Accessed 07Dec2019.
  27. 27.
    ISPE Facility of the Future. Accessed 15Dec2019.
  28. 28.
    Leurent, H, Boer, ED. The next economic growth engine: scaling fourth industrial revolution technologies in production. World Economic Forum. White paper, 2018.Google Scholar
  29. 29.
    Wilkinson MD, et al. The FAIR guiding principles for scientific data management and stewardship. Sci Data. 2016;3:1–9.CrossRefGoogle Scholar
  30. 30.
    Hausner DB, Moore CMV. Continuous Manufacturing Current Status. Pharmaceutical Engineering. 2018;38(May-June 2018):40–1. Accessed 11 Dec 2019.
  31. 31.
    Kesisoglou F, Hermans A, Neu C, Yee KL, Palcza J, Miller J. Development of in vitro–in vivo correlation for amorphous solid dispersion immediate-release suvorexant tablets and application to clinically relevant dissolution specifications and in-process controls. J Pharm Sci. 2015;104(9):2913–22.CrossRefGoogle Scholar
  32. 32.
    Sethi AK, Sethi SP. Flexibility in manufacturing: a survey. Int J Flex Manuf Syst. 1990;2:289–328.CrossRefGoogle Scholar
  33. 33.
    Products. SKAN AG. Accessed 06 Dec 2019.

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Yash Kapoor
    • 1
    Email author
  • Robert F. Meyer
    • 1
    Email author
  • Brian K. Meyer
    • 1
  • James C. DiNunzio
    • 1
  • Akhilesh Bhambhani
    • 1
  • Justin Stanbro
    • 1
  • Kristin J. M. Ploeger
    • 1
  • Erin N. Guidry
    • 1
  • Gregory M. Troup
    • 1
  • Adam T. Procopio
    • 1
  • Allen C. Templeton
    • 1
  1. 1.Merck & Co., Inc.KenilworthUSA

Personalised recommendations