Please cite this article in press Y. Achyutha Valli Devi et al., Quality By Design And Process Analytical Technology: A Conceptual Review Of Current Approach And Its Limitations., Indo Am. J. P. Sci, 2021; 08(08).

1. Rantanen, J, Khinast, J. The Future of Pharmaceutical Manufacturing Sciences. J Pharm Sci. [Online] 2015;(104): 3612–38. Available from: http://dx.doi.org/10.1002/jps.24594
2. Puñal peces, D, García-montoya, E, Manich, A, Suñé-negre, J.M, Pérez-lozano, P, Miñarro, M, Ticó, J.R. Approach to design space from retrospective quality data. Pharm Dev Technol. [Online] 2016; (21): 26–38.
Available from: http://dx.doi.org/10.3109/10837450.2014.965321
3. Koeberle, M, Schiemenz,W. QbD: Improving Pharmaceutical Development and Manufacturing Workflows to Deliver Better Patient Outcomes. Pharm. Technol. [Online] 2017; 20–23.
4. Ohage, E, Iverson, R, Krummen, L, Taticek, R,Vega, M. QbD implementation and Post Approval Lifecycle Management (PALM). Biologicals. [Online] 2016; (44): 332–340. Available from: http://dx.doi.org/10.1016/j.biologicals.2016.06.007
5. Reklaitis, G. V, Khinast, J, Muzzio, K. Pharmaceutical engineering science – New approaches to pharmaceutical development and manufacturing. Chem. Eng. Sci. [Online] 2010: iv–vii. Available from: http://dx.doi.org/10.1016/j.ces.2010.08.041
6. Yu,L. X, Kopcha, M. The future of pharmaceutical quality and the path to get there. Int. J. Pharm. [Online] 2017; 528: 354–359. Available from: http://dx.doi.org/10.1016/j.ijpharm.2017.06.039
7. Schlindwein, W. S, Gibson, M. Pharmaceutical quality by design: a practical approach. First ed., John Wiley & Sons Ltd., Chichester. 2018. Available from: http://dx.doi.org/10.1002/9781118895238
8. Uhlenbrock, L, Sixt, M, Strube, J. Quality-by-Design (QbD) process evaluation for phytopharmaceuticals on the example of 10-deacetylbaccatin III from yew. Resour. Technol. [Online] 2017; (3): 137–143. Available from: http://dx.doi.org/10.1016/J.REFFIT.2017.03.001
9. Juran, J. M, De Feo, J. A. Juran’s quality handbook: The complete guide to performance excellence, Sixth ed., McGraw Hill, New York, 2010.
10. Juran, J. M. Juran on Quality by Design: The new steps for planning quality into goods and services, First ed., Free Press, New York, 1992.
11. International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline: Q8 (R2) Pharmaceutical Development, 2009.
12. Food and Drug Administration (FDA. Final Report: Pharmaceutical cGMPs for the 21st Century – A risk-based approach, 2004.
13. International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline: Q9 Quality Risk Management, 2005.
14. International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline Pharmaceutical Quality System Q10, 2008.
15. International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline: Q11 Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities), 2012.
16. International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Guideline Technical: Q12 Product Lifecycle Management (draft version), 2017.
17. Food and Drug Administration (FDA). Guidance for Industry: Q8 (R2) Pharmaceutical Development, 2009.
18. Food and Drug Administration (FDA). Guidance for Industry: Q9 Quality Risk Management, 2006.
19. Food and Drug Administration (FDA). Guidance for Industry: Q10 Pharmaceutical Quality System, 2009.
20. Food and Drug Administration (FDA). Guidance for Industry: ICH Q11 Development and Manufacture of Drug Substances, 2012.
21. Food and Drug Administration (FDA). Guidance for Industry: Q8, Q9, and Q10 Questions and Answers, 2010.
22. International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline: Q13 Continuous Manufacturing of Drug Substances and Drug Products (Step 1 version), 2018.
23. Department of Health and Human Service – FDA, Guidance for Industry PAT- A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance, 2004.
24. Hinz, D. C. Process analytical technologies in the pharmaceutical industry: The FDA’s PAT initiative. Anal. Bioanal. Chem. [Online] 2006; (384): 1036–1042. Available from: http://dx.doi.org/10.1007/s00216-005-3394-y
25. Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Approval Letter for Januvia (sitagliptin phosphate). Application Number: 21-995, 2006.
26. Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Approval Package for Gazyva (obinutuzumab). Application Number: 125486Orig1s000, 2013.
27. European Medicines Agency (EMA). Committee for Medicinal Products for Human Use (CHMP). Assessment report for Gazyvaro (Obinutuzumab). Procedure No.: EMEA/H/C/002799, 2014.
28. European Medicines Agency (EMA). Committee for Medicinal Products for Human Use (CHMP). Assessment report for Kalydeco (Ivacaftor). Procedure No.: EMEA/H/C/002494, 2012.
29. Yu, L. X. Pharmaceutical Quality by Design: Product and Process Development, Understanding, and Control. Pharm. Res. [Online] 2008; (25): 781–791. Available from: http://dx.doi.org/10.1007/s11095-007-9511-1
30. U.S. Department of Health and Human Services – Food and Drug Administration (FDA). White paper: Challenge and Opportunity on the Critical Path to New Medical Technologies, 2004.
31. Suresh, P, Basu, P.K. Improving Pharmaceutical Product Development and Manufacturing: Impact on Cost of Drug Development and Cost of Goods Sold of Pharmaceuticals. J. Pharm. Innov. [Online] 2008; (3): 175–187. Available from: http://dx.doi.org/10.1007/s12247-008-9043-1
32. Clarivate Analytics. Web of Science Core Collection Help: Document Type Field, (n.d.). https://images.webofknowledge.com/images/help/WOS/hs_document_type.html
33. Fahmy, R, Kona, R, Dandu, R, Xie, W, Claycamp, G, Hoag, S. W. Quality by Design : Application of FMEA and Plackett–Burman Design of Experiments in the identification of “Main Factors” in the formulation and process design Space for roller-compacted ciprofloxacin hydrochloride immediaterelease tablets. AAPS PharmSciTech. [Online] 2012; (13): 1243–1254. Available from: http://dx.doi.org/10.1208/s12249-012-9844-x
34. Van den Ban, S, Pitt, K. G, Whiteman, M. Application of a tablet film coating model to define a process-imposed transition boundary for robust film coating. Pharm. Dev. Technol. [Online] 2018; (23): 176– 182. Available from: http://dx.doi.org/10.1080/10837450.2017.1384492
35. 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, Comput. Aided Chem. Eng. [Online] 2012; (31): 1095–1099. Available from: http://dx.doi.org/10.1016/B978-0-444-59506-5.50050-X
36. Lee, A. R, Kwon, S.Y, Choi, D. H, Park, E.S. Quality by Design (QbD) approach to optimize the formulation of a bilayer combination tablet (Telmiduo®) manufactured via high shear wet granulation. Int. J. Pharm. [Online] 2017; (534): 144–158. Available from: http://dx.doi.org/10.1016/j.ijpharm.2017.10.004
37. Kristan, K, Horvat, M. Rapid Exploration of Curing Process Design space for Production of Controlled‐Release Pellets. J. Pharm. Sci.[Online] 2012; (101): 3924–3935. Available from: http://dx.doi.org/10.1002/jps.23277
38. Hilden, J, Earle, G, Lilly, E. Prediction of roller compacted ribbon solid fraction for quality by design development. Powder Technol. [Online] 2011; (213): 1–13. Available from: http://dx.doi.org/10.1016/j.powtec.2011.05.025
39. Yerlikaya, F, Ozgen, A, Vural, I, Guven, O, Karaagaoglu, E, Khan, M. A, Capan, Y. Development and evaluation of paclitaxel nanoparticles using a quality-by-design approach. J. Pharm. Sci.[Online] 2013; (102): 3748–3761. Available from: http://dx.doi.org/10.1002/jps.23686
40. Tan, D.C.T, Chin, W.W.L, Tan, E.H, Hong, S, Gu, W, Gokhale, R. Effect of binders on the release rates of direct molded verapamil tablets using twin-screw extruder in melt granulation. Int. J. Pharm. [Online] 2014; (463): 89–97. Available from: http://dx.doi.org/10.1016/j.ijpharm.2013.12.053
41. Kapsi, S.G, Castro, L.D, Muller, F.X, Wrzosek, T.J. Development of a design space for a unit operation: Illustration using compression-mix blending process for the manufacture of a tablet dosage form. J. Pharm. Innov. [Online] 2012; (7): 19–29. Available from: http://dx.doi.org/10.1007/s12247-012-9122-1
42. Saripella, K.K, Loka, N.C, Mallipeddi, R, Rane, A.M, Neau, S.H. A Quality by Experimental Design Approach to Assess the Effect of Formulation and Process Variables on the Extrusion and Spheronization of Drug-Loaded Pellets Containing Polyplasdone® XL-10. AAPS Pharm. Sci. Tech. [Online] 2016; (17): 368–379. Available from: http://dx.doi.org/10.1208/s12249-015-0345-6
43. Khanolkar, A, Thorat, V, Raut, P, Samanta, G. Application of Quality by Design: Development to Manufacturing of Diclofenac Sodium Topical Gel. AAPS Pharm. Sci. Tech. 18 (2017) 2754–2763. Available from: http://dx.doi.org/10.1208/s1249-017-0755-8
44. Prpich, A, Am Ende, M.T, Katzschner, T, Lubczyk, V, Weyhers, H, Bernhard, G. Drug product modeling predictions for scale-up of tablet film coating – A quality by design approach. Comput. Chem. Eng. [Online] 2010; (34): 1092–1097. Available from: http://dx.doi.org/10.1016/j.compchemeng.2010.03.006
45. Hartung, A, Johansson, E, Knoell, M, Valthorsson, H, Langguth, P. “Design space” determination of a paracetamol fluid bed granulation using design of experiments. Pharm. Ind. [Online] 2012; (74): 644–650.
46. Wu, H, Khan, M.A. Quality-by-Design (QbD): An integrated approach for evaluation of powder blending process kinetics and determination of powder blending end-point. J. Pharm. Sci. [Online] 2009; (98): 2784–2798. Available from: http://dx.doi.org/10.1002/jps.21646
47. Tan, L, Carella, A.J, Ren, Y, Lo, J.B. Process optimization for continuous extrusion wet granulation. Pharm. Dev. Technol. [Online] 2011; (16): 302–315. Available from: http://dx.doi.org/10.3109/10837451003692587
48. Huang, J, Kaul, G, Cai, C, Chatlapalli, R, Hernandez-Abad, P, Ghosh, K, Nagi, A. Quality by design case study: An integrated multivariate approach to drug product and process development. Int. J. Pharm. [Online] 2009; (382): 23–32. Available from: http://dx.doi.org/10.1016/j.ijpharm.2009.07.031
49. [49] W. Grymonpré, V. Vanhoorne, B. Van Snick, B. Blahova Prudilova, F. Detobel, J.P. Remon, T. De Beer, C. Vervaet, Optimizing feed frame design and tableting process parameters to increase diefilling uniformity on a high-speed rotary tablet press, Int. J. Pharm. [Online] 2018; (548): 54–61. Available from: http://dx.doi.org/10.1016/J.IJPHARM.2018.06.047
50. Kushner, J, B.A. Langdon, Hicks,I, Song, D, Li, F, Kathiria, L, Kane, A, Ranade, G, Agarwal, K. A quality-by-design study for an immediate-release tablet platform: Examining the relative impact of active pharmaceutical ingredient properties, processing methods, and excipient variability on drug product quality attributes. J. Pharm. Sci. [Online] 2014; (103): 527–538. Available from: http://dx.doi.org/10.1002/jps.23810
51. Maniruzzaman,M, Nair, A, Renault, M, Nandi, U, Scoutaris,N, Farnish, R, Bradley, M.S.A, Snowden, M.J, Douroumis, D. Continuous twin-screw granulation for enhancing the dissolution of poorly water soluble drug. Int. J. Pharm. [Online] 2015; (496): 52–62. Available from: http://dx.doi.org/10.1016/j.ijpharm.2015.09.025
52. 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 Pharm. Sci. Tech. [Online] 2011; (12): 1324–1334. Available from: http://dx.doi.org/10.1208/s12249-011-9700-4
53. Kumar, S, Gokhale, R, Burgess, D.J. Quality by Design approach to spray drying processing of crystalline nanosuspensions. Int. J. Pharm. [Online] 2014; (464): 234–242. Available from: http://dx.doi.org/10.1016/j.ijpharm.2013.12.039
54. Kothari, B.H, Fahmy, R, Claycamp, H.G, Moore, C.M.V, Chatterjee, S, Hoag, S.W. A Systematic Approach of Employing QbD Principles: Risk Assessment and DoE to demonstrate process understanding and identify the critical process parameters for coating of the ethylcellulose pseudolatex dispersion using non-conventional fluid bed process. AAPS Pharm. Sci. Tech. [Online] 2017; (18): 1135–1157. Available from: http://dx.doi.org/10.1208/s12249-016-0569-0
55. Marto, J. Gouveia, L.F, Gonçalves, L.M, Gaspar, D.P, Pinto, P, Carvalho, F.A, Oliveira, E, Ribeiro, H.M, Almeida, A.J. A Quality by design (QbD) approach on starch-based nanocapsules: A promising platform for topical drug delivery, Colloids Surfaces B Biointerfaces. [Online] 2016; (143): 177–185. Available from: http://dx.doi.org/10.1016/J.COLSURFB.2016.03.039
56. Chavez, P.F, Lebrun, P, Sacré, P.Y, De Bleye, C, Netchacovitch, L, Cuypers, S, Mantanus, J, Motte, H, Schubert, M, Evrard, B, Hubert, P, Ziemons, E. Optimization of a pharmaceutical tablet formulation based on a design space approach and using vibrational spectroscopy as PAT tool. Int. J. Pharm. [Online] 2015; (486): 13–20. Available from: http://dx.doi.org/10.1016/j.ijpharm.2015.03.025
57. Cunningham, J.C, Winstead, D, Zavaliangos, A. Understanding variation in roller compaction through finite element-based process modeling, Comput. Chem. Eng. [Online] 2010; (34): 1058–1071. Available from: http://dx.doi.org/10.1016/j.compchemeng.2010.04.008
58. van den Ban, S, Goodwin, D.J. The Impact of Granule Density on Tabletting and Pharmaceutical Product Performance. Pharm. Res. [Online] 2017; (34): 1002–1011. Available from: http://dx.doi.org/10.1007/s11095-017-2115-5
59. Dumarey, M, Goodwin,D.J, Davison, C. Multivariate modelling to study the effect of the manufacturing process on the complete tablet dissolution profile. Int. J. Pharm. [Online] 2015; (486): 112–120. Available from: http://dx.doi.org/10.1016/j.ijpharm.2015.03.040
60. Belič, A, Škrjanc, I, Božič, D.J, Karba, R, Vrečer, F. Minimisation of the capping tendency by tableting process optimisation with the application of artificial neural networks and fuzzy models. Eur. J. Pharm. Biopharm. [Online] 2009; (73): 172–178. Available from: http://dx.doi.org/10.1016/J.EJPB.2009.05.005