Understanding pharmaceutical quality by design
Open accessAbstract
This review further clarifies the concept of pharmaceutical quality by design (QbD) and describes its objectives. QbD elements include the following: (1) a quality target product profile (QTPP) that identifies the critical quality attributes (CQAs) of the drug product; (2) product design and understanding including identification of critical material attributes (CMAs); (3) process design and understanding including identification of critical process parameters (CPPs), linking CMAs and CPPs to CQAs; (4) a control strategy that includes specifications for the drug substance(s), excipient(s), and drug product as well as controls for each step of the manufacturing process; and (5) process capability and continual improvement. QbD tools and studies include prior knowledge, risk assessment, mechanistic models, design of experiments (DoE) and data analysis, and process analytical technology (PAT). As the pharmaceutical industry moves toward the implementation of pharmaceutical QbD, a common terminology, understanding of concepts and expectations are necessary. This understanding will facilitate better communication between those involved in risk-based drug development and drug application review.
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Characterization of the impact of changes to process parameters on critical quality attributes, such as by using design of experiments, improves understanding of the process, enables its optimization, and ultimately assures product quality by design.
“The characterization of the impact of changes to process parameters on these CQAs, such as by using design of experiments,9 improves understanding of the process, enables its optimization, and ultimately assures product quality by design (Table 1).10, 11, 12”
From Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies (2021) · cites this paper as [10]
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Cites
Pharmaceutical Quality by Design: Product and Process Development, Understanding, and Control
Yu, L. X. (2008) · Pharmaceutical Research · doi:10.1007/s11095-007-9511-1 · Cited by 1,192 · see citing works
Self-citationQuality by design for biopharmaceuticals
Rathore, A., & Winkle, H. (2009) · Nature Biotechnology · doi:10.1038/nbt0109-26 · Cited by 891 · see citing works
Juran on Quality by Design: The New Steps for Planning Quality into Goods and Services
Juran, J. M. (1992) · Cited by 609 · see citing works
Quality by Design in Biopharmaceuticals
Yang, H. (2016) · doi:10.1201/9781315371726-7 · Cited by 545 · see citing works
Quality by Design: Concepts for ANDAs
Lionberger, R. A., Lee, S. L., Lee, L., et al. (2008) · The AAPS Journal · doi:10.1208/s12248-008-9026-7 · Cited by 390 · see citing works
Applications of process analytical technology to crystallization processes
Yu, L. (2003) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2003.10.012 · Cited by 325 · see citing works
Self-citationSupac-Mr: Modified Release Solid Oral Dosage Forms—Scale-Up and Postapproval Changes
(2001) · Drugs and the pharmaceutical sciences · doi:10.1201/9780824741969.axb · Cited by 192 · see citing works
Nazzal, S., Nutan, M. T. H., Palamakula, A., Shah, R. B., Zaghloul, A.-A. A., & Khan, M. A. (2002) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(02)00130-8 · Cited by 147 · see citing works
Self-citationZidan, A. S., Sammour, O. A., Hammad, M. A., et al. (2006) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2006.09.060 · Cited by 137 · see citing works
Juran Institute's six sigma : breakthrough and beyond : quality performance breakthrough methods
Feo, J. A. D., Barnard, W. W., & Juran, J. M. (2004) · McGraw-Hill eBooks · Cited by 131 · see citing works
Xu, X., Khan, M. A., & Burgess, D. J. (2011) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2011.11.036 · Cited by 127 · see citing works
Self-citationWu, H., White, M., & Khan, M. A. (2010) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2010.11.045 · Cited by 112 · see citing works
Self-citationDevelopment and Evaluation of Paclitaxel Nanoparticles Using a Quality-by-Design Approach
Yerlikaya, F., Ozgen, A., Vural, İ., et al. (2013) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23686 · Cited by 95 · see citing works
Wu, H., Tawakkul, M. A., White, M., & Khan, M. A. (2009) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2009.01.002 · Cited by 94 · see citing works
Self-citationAwotwe‐Otoo, D., Agarabi, C. D., Wu, G. K., Casey, E., Read, E. K., Lute, S. C., Brorson, K., Khan, M. A., & Shah, R. B. (2012) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2012.08.033 · Cited by 91 · see citing works
Self-citationWu, H., & Khan, M. A. (2009) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21646 · Cited by 64 · see citing works
Self-citationPharmaceutical Equivalence by Design for Generic Drugs: Modified-Release Products
Raw, A., Lionberger, R. A., & Yu, L. X. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0397-6 · Cited by 48 · see citing works
Self-citationRahman, Z., Siddiqui, A., & Khan, M. A. (2013) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2013.06.006 · Cited by 38 · see citing works
Self-citationRahman, Z., Siddiqui, A., & Khan, M. A. (2013) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2013.07.049 · Cited by 29 · see citing works
Self-citationWu, H., & Khan, M. A. (2010) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22430 · Cited by 16 · see citing works
Self-citationRahman, Z., & Khan, M. A. (2013) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2013.07.062 · Cited by 14 · see citing works
Self-citationRahman, Z., Siddiqui, A., & Khan, M. A. (2013) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23740 · Cited by 10 · see citing works
Self-citationFocused beam reflectance measurement to monitor nimodipine precipitation process
Xu, X., Siddiqui, A., & Khan, M. A. (2013) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2013.08.083 · Cited by 7 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 3
- [23]USP 34—NF 29 (United States Pharmacopeial Convention). Chapter 1078. Good manufacturing practice for bulk pharmaceutical excipients. Rockville, MD: USP; 2011, pp. 1415–1420
- [24]USP 34—NF 29 (United States Pharmacopeial Convention). USP and NF Excipients, Listed by Category. Rockville, MD: USP; 2011, pp. 583–595.
- [29]Glodek M, Liebowitz S, McCarthy R, McNally G, Oksanen C, Schultz T, et al. Process robustness—a PQRI white paper. Pharm Eng. 2006;26:1–11. [Google Scholar]
Cited by
Sorted by citations
Gimpel, A. L., Katsikis, G., Sha, S., Maloney, A. J., Hong, M. S., Nguyen, T. N. T., Wolfrum, J., Springs, S. L., Sinskey, A. J., Manalis, S. R., et al. (2021) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2021.02.010 · Cited by 185 · see citing works
Ha, T. K., Kim, D., Kim, C. L., Grav, L. M., & Lee, G. M. (2022) · Biotechnology Advances · doi:10.1016/j.biotechadv.2021.107831 · Cited by 74 · see citing works
Margolskee, A., Darwich, A. S., Pepin, X., Aarons, L., Galetin, A., Rostami-Hodjegan, A., Carlert, S., Hammarberg, M., Hilgendorf, C., Johansson, P., et al. (2017) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2016.10.036 · Cited by 69 · see citing works
Narukulla, S., Bogadi, S., Tallapaneni, V., Sanapalli, B. K. R., Sanju, S., Khan, A. A., Malik, A., Barai, H. R., Mondal, T. K., Karri, V. V. S. R., et al. (2024) · Microchemical Journal · doi:10.1016/j.microc.2024.111875 · Cited by 52 · see citing works
Advancing product quality: a summary of the second FDA/PQRI conference
Yu, L. X., Akseli, I., Allen, B., Amidon, G., Bizjak, T. G., Boam, A., Caulk, M., Doleski, D., Famulare, J., Fisher, A. C., et al. (2016) · The AAPS Journal · doi:10.1208/s12248-016-9874-5 · Cited by 33 · see citing works
Self-citationCurrent <scp>GMP</scp> standards for the large‐scale production of monoclonal antibodies
Troncoso‐Bravo, T., Pavez, V., Letelier, P., Del Río, J., Anabalón, C., Peñaloza, H. F., González, P. A., Bueno, S. M., & Kalergis, A. M. (2026) · Bioengineering & Translational Medicine · doi:10.1002/btm2.70121 · Cited by 2 · see citing works
- Authors
- Yu, L. X., Amidon, G., Khan, M. A., Hoag, S. W., Polli, J., Raju, G. K., & Woodcock, J.
- Affiliations
- United States Food and Drug Administration (US)
- University of Michigan (US)
- University of Maryland, Baltimore (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Yu, Lawrence X.
- Venue
- The AAPS Journal
- Published
- 2014-05-23
- Volume
- 16
- Issue
- 4
- Pages
- 771-783
- ISSN
- 1550-7416 (ISSN-L)
- PMC
- PMC4070262
- OpenAlex
- W1999481657
- Cited by
- 1,475
- References
- 23
- Citations by year
- 2026: 183 · 2025: 193 · 2024: 178 · 2023: 155 · 2022: 143 · 2021: 144 · 2020: 118 · 2019: 116 · 2018: 106 · 2017: 60 · 2016: 47 · 2015: 28 · 2014: 2
- FWCI
- 40.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- The AAPS Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Springer US
- Topics
- Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Physical Sciences › Engineering › Computational Mechanics › Granular flow and fluidized beds
- Keywords
- quality by design, quality target product profile, critical quality attributes, critical material attributes, critical process parameters, control strategy, process analytical technology, risk assessment, experimental design, mechanistic model, process capability, continuous improvement, drug development, regulatory review
- MeSH terms
- Chemistry, Pharmaceutical, Drug Industry, Pharmaceutical Preparations, Humans, Technology, Pharmaceutical, Drug Design, Quality Improvement
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