Skip to content
2000
image of A Review on Process Analytical Technology as a Driver of Pharmaceutical Manufacturing for the Improvement of Quality while Reducing Costs

Abstract

Process analytical technology has emerged as a possible game-changing platform in the pharmaceutical business to improve process knowledge while also improving product quality and lowering production costs. This paper outlines the underlying principles of PAT, its application in pharmaceutical manufacturing processes, and the impact on assurance of quality and reduction of cost. Real-time monitoring, multivariate data analysis, and process control strategies are three modules that are computed and integrated with PAT to develop robust and efficient manufacturing processes. A number of case studies and examples have been used to illustrate this relationship between the implementation of PAT and a reduction in variability with an improvement in process control and consistency of the product, which finally realizes million-dollar savings. It also debates the regulatory perspectives and challenges involved in PAT adoption, focusing on how stakeholders in the industry and agencies can integrate in developing and implementing innovations that will pass the test of compliance criteria. In general, what this paper presents is that PAT will drive pharmaceutical manufacturing into advancement for higher standards of quality with increased efficiency.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cds/10.2174/0115748863374678250501184523
2025-05-16
2025-09-10

  • From This Site

    /content/journals/cds/10.2174/0115748863374678250501184523
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Rathore A.S. Bhambure R. Ghare V. Process analytical technology (PAT) for biopharmaceutical products. Anal. Bioanal. Chem. 2010 398 1 137 154 10.1007/s00216‑010‑3781‑x 20480150
    [Google Scholar]
  2. Chanda A. Daly A.M. Foley D.A. LaPack M.A. Mukherjee S. Orr J.D. Reid G.L. III Thompson D.R. Ward H.W. II Industry perspectives on process analytical technology: tools and applications in API development. Org. Process Res. Dev. 2015 19 1 63 83 10.1021/op400358b
    [Google Scholar]
  3. Guidance for industry PAT - A framework for innovative pharmaceutical development, manufacturing, and quality assurance. 2004 Available from: https://www.fda.gov/media/71012/download
  4. Munson J. Freeman Stanfield C. Gujral B. A review of Process Analytical Technology (PAT) in the U.S. pharmaceutical industry. Curr. Pharm. Anal. 2006 2 4 405 414 10.2174/157341206778699582
    [Google Scholar]
  5. Lopes J.A. Process analytical technology: spectroscopic tools and implementation strategies for the chemical and pharmaceutical industries. Katherine A. Bakeev, Blackwell Publishing Ltd., Oxford, 2005, 451 pp, ISBN 1-4051-2103-3. J. Chemometr. 2005 19 11-12 668 669 10.1002/cem.969
    [Google Scholar]
  6. Simpson M.B. Near-infrared spectroscopy for process analytical chemistry: Theory, technology and implementation. Process Analytical Technology Wiley Bakeev K.A. 2005 39 90 10.1002/9780470988459.ch3
    [Google Scholar]
  7. Scott P. Process analytical technology: Applications to the pharmaceutical industry. Available from: https://dissolutiontech.com/DTresour/0802art/Article_1.htm (Accessed on: 25 May 2013)
  8. Grumbach C. Czermak P. Process analytical technology for the production of parenteral lipid emulsions according to good manufacturing practices. Processes (Basel) 2022 10 6 1174 10.3390/pr10061174
    [Google Scholar]
  9. Gifford J. Albee A. Deeds Z.W. Delong B. Kao K. Ross J.S. Caple M.V. An efficient approach to cell culture medium optimization — A statistical method to medium mixing. Animal Cell Technology Meets Genomics Dordrecht Springer Gòdia F. Fussenegger M. 549 553 10.1007/1‑4020‑3103‑3_108
    [Google Scholar]
  10. Kamble R.N. Sharma S. Varghese V. Mahadik K.R. Process analytical technology (PAT) in pharmaceutical development and its application. Int. J. Pharm. Sci. Rev. Res. 2013 23 2 212 223
    [Google Scholar]
  11. Reid G.L. Ward H.W. Palm A.S. Muteki K. Process Analytical Technology (PAT) in pharmaceutical development. Am. Pharm. Rev. 2012 15 4 49
    [Google Scholar]
  12. Abraham J. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. Handbook of Transnational Economic Governance Regimes Brill 2010 1041 1053 10.1163/ej.9789004163300.i‑1081.897
    [Google Scholar]
  13. Alimagham F. Winterburn J. Dolman B. Domingues P.M. Everest F. Platkov M. Basov S. Izakson G. Katzir A. Elliott S.R. Hutter T. Real-time bioprocess monitoring using a mid-infrared fibre-optic sensor. Biochem. Eng. J. 2021 167 107889 10.1016/j.bej.2020.107889
    [Google Scholar]
  14. Nestle N. Lim Z.J. Böhringer T. Abtmeyer S. Arenz S. Leinweber F.C. Weiß T. von Harbou E. Taking compact NMR to monitoring real reactions in large-scale chemical industries - General considerations and learnings from a lab-scale test case. Magn. Reson. Chem. 2020 58 12 1213 1221 10.1002/mrc.5061
    [Google Scholar]
  15. ICH guideline Q11 on development and manufacture of drug substances (chemical entities and biotechnological/biological entities). 2011 Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/draft-ich-guideline-q11-development-and-manufacture-drug-substances-chemical-entities-and-biotechnological-biological-entities_en.pdf
  16. International Conference on Harmonization (ICH) Q9, quality risk management. 2005 Available from: https://database.ich.org/sites/default/files/Q9_Guideline.pdf
  17. Cogdill R.P. Anderson C.A. Drennen J.K. Using NIR spectroscopy as an Integrated PAT Tool. Spectroscopy (Springf.) 2004 19 12 104 109
    [Google Scholar]
  18. Alcalà M. León J. Ropero J. Blanco M. Romañach R.J. Analysis of low content drug tablets by transmission near infrared spectroscopy: Selection of calibration ranges according to multivariate detection and quantitation limits of PLS models. J. Pharm. Sci. 2008 97 12 5318 5327 10.1002/jps.21373 18351596
    [Google Scholar]
  19. Johansson J. Sparén A. Svensson O. Folestad S. Claybourn M. Quantitative transmission Raman spectroscopy of pharmaceutical tablets and capsules. Appl. Spectrosc. 2007 61 11 1211 1218 10.1366/000370207782597085 18028700
    [Google Scholar]
  20. Sekulic S.S. Ward H.W. Brannegan D.R. Stanley E.D. Evans C.L. Sciavolino S.T. Hailey P.A. Aldridge P.K. On-line monitoring of powder blend homogeneity by near-infrared spectroscopy. Anal. Chem. 1996 68 3 509 513 10.1021/ac950964m 21619087
    [Google Scholar]
  21. Igne B. Zacour B.M. Shi Z. Talwar S. Anderson C.A. Drennen J.K. III Online monitoring of pharmaceutical materials using multiple NIR sensors — Part I: Blend homogeneity. J. Pharm. Innov. 2011 6 1 47 59 10.1007/s12247‑011‑9099‑1
    [Google Scholar]
  22. Corredor C.C. Bu D. Both D. Comparison of near infrared and microwave resonance sensors for at-line moisture determination in powders and tablets. Anal. Chim. Acta 2011 696 1-2 84 93 10.1016/j.aca.2011.03.048 21621036
    [Google Scholar]
  23. Muteki K. Swaminathan V. Sekulic S.S. Reid G.L. De-risking pharmaceutical tablet manufacture through process understanding, latent variable modeling, and optimization technologies. AAPS PharmSciTech 2011 12 4 1324 1334 10.1208/s12249‑011‑9700‑4 21969245
    [Google Scholar]
  24. Muteki K. Yamamoto K. Reid G.L. Krishnan M. De-risking scale-up of a high shear wet granulation process using latent variable modeling and near-infrared spectroscopy. J. Pharm. Innov. 2011 6 3 142 156 10.1007/s12247‑011‑9110‑x
    [Google Scholar]
  25. Singh R, Muzzio F, Ierapetritou M, Ramachandran R. A Combined Feed-Forward/Feed-Back Control System for a QbD-Based Continuous Tablet Manufacturing Process. Processes. 2015 3 2 339 56
    [Google Scholar]
  26. Schlindwein W.S. Gibson M. Pharmaceutical Quality by Design: A Practical Approach Wiley 2018 10.1002/9781118895238
    [Google Scholar]
  27. Patel M.N. Kothari C.S. Review on implementation of multivariate approach for forced degradation study and impurity profiling with regulatory considerations. Chromatographia 2018 81 1 105 125 10.1007/s10337‑017‑3393‑0
    [Google Scholar]
  28. Namuduri S. Narayanan B.N. Davuluru V.S.P. Burton L. Bhansali S. Review - Deep learning methods for sensor based predictive maintenance and future perspectives for electrochemical sensors. J. Electrochem. Soc. 2020 167 3 037552 10.1149/1945‑7111/ab67a8
    [Google Scholar]
  29. Hamilton P. Sanganee M.J. Graham J.P. Hartwig T. Ironmonger A. Priestley C. Senior L.A. Thompson D.R. Webb M.R. Using PAT to understand, control, and rapidly scale up the production of a hydrogenation reaction and isolation of pharmaceutical intermediate. Org. Process Res. Dev. 2015 19 1 236 243 10.1021/op500285x
    [Google Scholar]
  30. Naidu V.R. Deshpande R.S. Syed M.R. Deoghare P. Singh D. Wakte P.S. PAT-based control of fluid bed coating process using NIR spectroscopy to monitor the cellulose coating on pharmaceutical pellets. AAPS PharmSciTech 2017 18 6 2045 2054 10.1208/s12249‑016‑0680‑2 27995464
    [Google Scholar]
  31. Lander V. Cycle time reduction in manufacturing using a scientific data management system, chimicaoggi. Chemistry Today 2004 March/April 14 16
    [Google Scholar]
  32. Manufacturing and processing, providing a global perspective on the pharmaceutical industry. World Pharm. Front. 2004 32 36
    [Google Scholar]
  33. Marsaco Corinne A. Pharma's process analytical technology. Chem. Eng. News 2005 83 8 201 206 10.1021/cen‑v083n008.p201
    [Google Scholar]
  34. Frank I.E. Kowalski B.R. Chemometrics. Anal. Chem. 1982 54 5 232 243 10.1021/ac00242a023
    [Google Scholar]
  35. Lavine B.K. Workman J. Chemometric. Anal. Chem. 2002 74 12 2763 2769 10.1021/ac020224v 12090663
    [Google Scholar]
  36. Hussain A. PAT guidance: Going from current negative vocabulary to manufacturing science enabling vocabulary. 2004
    [Google Scholar]
  37. Warnecke S. Rinnan Å. Allesø M. Engelsen S.B. Fluorescence spectroscopy in process analytical technology (PAT): Simultaneous quantification of two active pharmaceutical ingredients in a tablet formulation. Appl. Spectrosc. 2015 69 3 323 331 10.1366/14‑07470 25760291
    [Google Scholar]
  38. López-Arellano R. Santander-García E.A. Andrade-Garda J.M. Alvarez-Avila G. Garduño-Rosas J.A. Morales-Hipólito E.A. Quantification of lysine clonixinate in intravenous injections by NIR spectroscopy. Vib. Spectrosc. 2009 51 2 255 262 10.1016/j.vibspec.2009.07.001
    [Google Scholar]
  39. Ghita M. Neckebroek M. Muresan C. Copot D. Closed-loop control of anesthesia: Survey on actual trends, challenges and perspectives. IEEE Access 2020 8 206264 206279 10.1109/ACCESS.2020.3037725
    [Google Scholar]
  40. Gioiello A. Piccinno A. Lozza A.M. Cerra B. The medicinal chemistry in the era of machines and automation: Recent advances in continuous flow technology. J. Med. Chem. 2020 63 13 6624 6647 10.1021/acs.jmedchem.9b01956 32049517
    [Google Scholar]
  41. Kim E.J. Kim J.H. Kim M.S. Jeong S.H. Choi D.H. Process analytical technology tools for monitoring pharmaceutical unit operations: A control strategy for continuous process verification. Pharmaceutics 2021 13 6 919 10.3390/pharmaceutics13060919 34205797
    [Google Scholar]
  42. Guenard R. Thurau G. Implementation of PAT. Process Analytical Technology: Spectroscopic Tools and Implementation Strategies for the Chemical and Pharmaceutical Industries New York Wiley Bakeev K.A. 2010 17 36 10.1002/9780470689592.ch2
    [Google Scholar]
  43. Helmdach L. Feth M.P. Minnich C. Ulrich J. Application of ATR-MIR spectroscopy in the pilot plant - Scope and limitations using the example of Paracetamol crystallizations. Chem. Eng. Process. 2013 70 184 197 10.1016/j.cep.2013.04.003
    [Google Scholar]
  44. Tamrakar A. Chen S.W. Ramachandran R. A DEM model-based study to quantitatively compare the effect of wet and dry binder addition in high-shear wet granulation processes. Chem. Eng. Res. Des. 2019 142 307 326 10.1016/j.cherd.2018.12.016
    [Google Scholar]
  45. Van Volsem S. A method for determining cost-efficient inspection strategies in multistage production systems. 4OR 2007 5 343 346 10.1007/s10288‑006‑0030‑4
    [Google Scholar]
  46. Kamran S. Impact of process analytical technology on reducing production costs and improving process reliability. J. Chem. Eng. Process Technol. 2024 15 3 514 10.35248/2157‑7048.24
    [Google Scholar]
  47. Glassey J. Gernaey K.V. Clemens C. Schulz T.W. Oliveira R. Striedner G. Mandenius C.F. Process analytical technology (PAT) for biopharmaceuticals. Biotechnol. J. 2011 6 4 369 377 10.1002/biot.201000356 21416609
    [Google Scholar]
  48. Das S.S. Alkahtani S. Nayak A.K. Hasnain M.S. Chapter 8 - Process analytical technology (PAT) tools: Uses in pharmaceutical manufacturing. Advances and Challenges in Pharmaceutical Technology Academic Press Nayak A.K. Pal K. Banerjee I. Maji S. Nanda U. 2021 243 259 10.1016/B978‑0‑12‑820043‑8.00007‑4
    [Google Scholar]
  49. Simon L.L. Pataki H. Marosi G. Meemken F. Hungerbühler K. Baiker A. Tummala S. Glennon B. Kuentz M. Steele G. Kramer H.J.M. Rydzak J.W. Chen Z. Morris J. Kjell F. Singh R. Gani R. Gernaey K.V. Louhi-Kultanen M. O’Reilly J. Sandler N. Antikainen O. Yliruusi J. Frohberg P. Ulrich J. Braatz R.D. Leyssens T. von Stosch M. Oliveira R. Tan R.B.H. Wu H. Khan M. O’Grady D. Pandey A. Westra R. Delle-Case E. Pape D. Angelosante D. Maret Y. Steiger O. Lenner M. Abbou-Oucherif K. Nagy Z.K. Litster J.D. Kamaraju V.K. Chiu M-S. Assessment of recent process analytical technology (PAT) trends: A multiauthor review. Org. Process Res. Dev. 2015 19 1 3 62 10.1021/op500261y
    [Google Scholar]
  50. Rolinger L. Rüdt M. Hubbuch J. A critical review of recent trends, and a future perspective of optical spectroscopy as PAT in biopharmaceutical downstream processing. Anal. Bioanal. Chem. 2020 412 9 2047 2064 10.1007/s00216‑020‑02407‑z 32146498
    [Google Scholar]
  51. Li X. Recent applications of quantitative mass spectrometry in biopharmaceutical process development and manufacturing. J. Pharm. Biomed. Anal. 2023 234 115581 10.1016/j.jpba.2023.115581 37494866
    [Google Scholar]
  52. Klukovich H.M. Facilitating Adoption of Continuous Manufacturing Platforms in the Pharmaceutical Industry. Master of Science, Massachusetts Institute of Technology 2023
    [Google Scholar]
  53. Fontalvo-Lascano M. Méndez-Piñero M. Romañach R. Design and development of a cost model for the implementation of process analytical technology in the pharmaceutical industry. Proceedings of the 9th Annual World Conference of the Society for Industrial and Systems Engineering, Virtual Conference Sep. 17-18, 2020, pp. 62-67.
    [Google Scholar]
  54. Ayati N. Saiyarsarai P. Nikfar S. Short and long term impacts of COVID-19 on the pharmaceutical sector. Daru 2020 28 2 799 805 10.1007/s40199‑020‑00358‑5 32617864
    [Google Scholar]
  55. Závadská Z. Závadský J. Quality managers and their future technological expectations related to Industry 4.0. Total Qual. Manage. Bus. Excell. 2020 31 7-8 717 741 10.1080/14783363.2018.1444474
    [Google Scholar]
  56. Marques C.M. Moniz S. de Sousa J.P. Barbosa-Povoa A.P. Reklaitis G. Decision-support challenges in the chemical-pharmaceutical industry: Findings and future research directions. Comput. Chem. Eng. 2020 134 106672 10.1016/j.compchemeng.2019.106672
    [Google Scholar]
  57. Yang Y. Pal K. Koswara A. Sun Q. Zhang Y. Quon J. McKeown R. Goss C. Nagy Z.K. Application of feedback control and in situ milling to improve particle size and shape in the crystallization of a slow growing needle-like active pharmaceutical ingredient. Int. J. Pharm. 2017 533 1 49 61 10.1016/j.ijpharm.2017.09.050 28935256
    [Google Scholar]
  58. Matthews H.B. Rawlings J.B. Batch crystallization of a photochemical: Modeling, control, and filtration. AIChE J. 1998 44 5 1119 1127 10.1002/aic.690440510
    [Google Scholar]
  59. Fujiwara M. Chow P.S. Ma D.L. Braatz R.D. Paracetamol crystallization using laser backscattering and ATR-FTIR spec troscopy: Metastability, agglomeration, and control. Cryst. Growth Des. 2002 2 5 363 370 10.1021/cg0200098
    [Google Scholar]
  60. Gao Y. Zhang T. Ma Y. Xue F. Gao Z. Hou B. Gong J. Application of PAT-based feedback control approaches in pharmaceutical crystallization. Crystals (Basel) 2021 11 3 221 10.3390/cryst11030221
    [Google Scholar]
  61. Zhao B. Zang H. Zhong L. Ma X. Wang H. Zhang H. Li L. Review of the application of PAT in the pharmaceutical continuous crystallization process. Curr. Top. Med. Chem. 2023 23 18 1699 1714 10.2174/1568026623666230420112709 37078345
    [Google Scholar]
/content/journals/cds/10.2174/0115748863374678250501184523
Loading
A Review on Process Analytical Technology as a Driver of Pharmaceutical Manufacturing for the Improvement of Quality while Reducing Costs
Bentham Science Publishers ; https://doi.org/10.2174/0115748863374678250501184523
/content/journals/cds/10.2174/0115748863374678250501184523
/content/journals/cds/10.2174/0115748863374678250501184523
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: process control ; cost reduction ; Process analytical technology ; quality by design ; quality assurance ; real-time monitoring

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test