Pharmaceutical Quality by Design: Product and Process Development, Understanding, and Control
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The purpose of this paper is to discuss the pharmaceutical Quality by Design (QbD) and describe how it can be used to ensure pharmaceutical quality.
Materials and Methods
The QbD was described and some of its elements identified. Process parameters and quality attributes were identified for each unit operation during manufacture of solid oral dosage forms. The use of QbD was contrasted with the evaluation of product quality by testing alone.
Defining target product quality profile
Designing product and manufacturing processes
Identifying critical quality attributes, process parameters, and sources of variability
Controlling manufacturing processes to produce consistent quality over time
Using QbD, pharmaceutical quality is assured by understanding and controlling formulation and manufacturing variables. Product testing confirms the product quality. Implementation of QbD will enable transformation of the chemistry, manufacturing, and controls (CMC) review of abbreviated new drug applications (ANDAs) into a science-based pharmaceutical quality assessment.
Key Wordspharmaceutical quality by design pharmaceutical quality by testing process control process design process parameter process variability product design quality attribute question-based review
The authors would like to thank Drs. Gregory Amidon, Yihong Qiu, John Strong, Alan Parr, Mansoor Khan, Vincent Vilker, Robert Lionberger, Andre Raw, Lai Ming Lee, Lawrence Sau Lee, Wallace Adams, Doan Nguyen, Michelle Bryden, Gary Buehler, Helen Winkle, and Janet Woodcock for their valuable suggestions.
- 1.Food and Drug Administration (2003). Final report on pharmaceutical cGMPs for the 21st century—A risk-based approach. http://www.fda.gov/cder/gmp/gmp2004/GMP_finalreport2004.htm (Accessed April 6, 2005).
- 3.Food and Drug Administration CDER. Guidance for industry, Q8 pharmaceutical development (May 2006).Google Scholar
- 4.M. Nasr. Risk-based CMC review paradigm. Advisory committee for pharmaceutical science meeting, July 20–21, 2004.Google Scholar
- 5.Food and Drug Administration CDER. Guidance for industry: Immediate release solid oral dosage forms scale-up and postapproval changes: Chemistry, manufacturing, and controls, in vitro dissolution testing, and in vivo bioequivalence documentation (November 1995).Google Scholar
- 6.Food and Drug Administration CDER. Guidance for industry: Modified release solid oral dosage forms scale-up and postapproval changes: Chemistry, manufacturing, and controls, in vitro dissolution testing, and in vivo bioequivalence documentation (September 1997).Google Scholar
- 7.Food and Drug Administration CDER. Guidance for industry: Nonsterile semisolid dosage forms scale-up and postapproval changes: chemistry, manufacturing, and controls, in vitro dissolution testing, and in vivo bioequivalence documentation (May 1997).Google Scholar
- 8.Food and Drug Administration CDER. Guidance for industry: Changes to an approved NDA or ANDA (April 2004).Google Scholar
- 9.J. Woodcock. The concept of pharmaceutical quality. Am. Pharm. Rev. November–December, 1–3, 2004.Google Scholar
- 10.Food and Drug Administration Office of Generic Drugs White Paper on Question-based Review. http://www.fda.gov/cder/OGD/QbR.htm.
- 11.Food and Drug Administration CDER. Guidance for industry, Q6A specifications for new drug substances and products: Chemical substances (October 1999).Google Scholar
- 12.M. Nasr. FDA’s quality initiatives: An update. http://www.gmp-compliance.com/daten/download/FDAs_Quality_Initiative.pdf (Accessed Nov. 10, 2007).
- 13.IBM Business Consulting Services (2005). Transforming industrialization: A new paradigm for pharmaceutical development. http://www-935.ibm.com/services/us/imc/pdf/ge510–3997-transforming-industrialization.pdf (Accessed November 16, 2006).
- 14.Food and Drug Administration. http://www.fda.gov/ohrms/dockets/ac/06/minutes/2006–4228m1.pdf (Accessed November 16, 2006).
- 15.H. Zhang, and L. X. Yu. Dissolution testing for solid oral drug products: Theoretical considerations. Am. Pharm. Rev., September, 26–31, 2004.Google Scholar
- 18.Food and Drug Administration CDER. Guidance for industry, Q3B (R2) impurities in new drug product (July 2006).Google Scholar
- 19.Food and Drug Administration CDER. Draft guidance for industry, ANDAs: Impurities in drug products (August 2005).Google Scholar
- 20.J. M. Delasko, D. M. Cocchetto, and L. B. Burke. Target product profile: Beginning drug development with the end in mind. Update, January/February, Issue 1, 2005, http://www.fdli.org.
- 21.Food and Drug Administration CDER. Draft guidance for industry and review staff: Target product profile—A strategic development tool (March 2007).Google Scholar
- 22.Food and Drug Administration Office of Generic Drugs. Model quality overall summary for IR product. http://www.fda.gov/cder/ogd/OGD_Model_QOS_IR_Product.pdf (Accessed March 31, 2006).
- 23.G. E. Amidon, X. He, M. J. Hageman. Burgers medicinal chemistry and drug discovery, vol 2., Ch 18. In D. J. Abraham (eds). Wiley-Interscience, New York, 2004.Google Scholar
- 24.L. X. Yu, M. S. Furness, A. Raw, K. P. Woodland Outlaw, N. E. Nashed, E. Ramos, S. P. F. Miller, R. C. Adams, F. Fang, R. M. Patel, F. O. Holcombe Jr., Y. Chiu, and A. S. Hussain. Scientific considerations of pharmaceutical solid polymorphism in abbreviated new drug applications. Pharm. Res 20:531–536 (2003).PubMedCrossRefGoogle Scholar
- 26.S. P. F. Miller, A. S. Raw, and L. X. Yu. FDA perspective on pharmaceutical solid polymorphism. In R. Hilfiker (ed.), Polymorphism—In the Pharmaceutical and Fine Chemical Industry, Wiley-VCH, New York, 2006.Google Scholar
- 27.G. E. Amidon. Intrinsic properties of drug substance, excipients, and process selection. FDA OGD regulatory science training series. Manufacturing science and scale-up challenges. May 23, 2005.Google Scholar
- 28.D. Sun, L. X. Yu, M. A. Hussain, D. A. Wall, R. L. Smith, and G. L. Amidon. In Vitro testing of drug absorption for drug “developability” assessment: Forming an interface between in vitro preclinical data and clinical outcome. Curr Opin Drug Discov Devel. 7:75–85 (2004).Google Scholar
- 30.L. X. Yu, C. D. Ellison, and A. S. Hussain. Predicting human oral bioavailability using in silico models. In R. Krishna (ed.), Applications of Pharmacokinetics Principles in Drug Development, Kluwer, New York, 2004.Google Scholar
- 32.Food and Drug Administration CDER. Guidance for industry, Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System. August 2000, CDER/FDA.Google Scholar
- 34.J. E. Polli, L. X. Yu, J. A. Cook, G. L. Amidon, R. T. Borchardt, B. A. Burnside, P. S. Burton, M. L. Chen, D. P. Conner, P. J. Faustino, A. A. Hawi, A. S. Hussain, H. N. Joshi, G. Kwei, V. H. L. Lee, L. J. Lesko, R. A. Lipper, A. E. Loper, S. G. Nerurkar, J. W. Polli, D. R. Srdeker, R. Taneja, R. S. Uppoor, C. S. Vattikonda, I. Wilding, and G. Zhang. Summary workshop report: Biopharmaceutics classification system – implementation challenges and extension opportunities. J. Pharm. Sci 93:1375–81 (2004).PubMedCrossRefGoogle Scholar
- 35.G. E. Amidon. Physical and mechanical property characterization of powders. In H. G. Brittain (ed.), Physical Characterization of Pharmaceutical Solid. Marcel Dekker, New York 1995, pp. 281–320.Google Scholar
- 36.S. Jain. Mechanical properties of powders for compaction and tableting: an overview. PSTT 2:20–31 (1999).Google Scholar
- 37.H. Dubin. Formulation frustrations. Drug Deliv. Technol. 5(8), 2005 (September).Google Scholar
- 40.R. Kandarapu, V. Grover, H. P. S. Chawla, and S. Garg. S. T. P. Pharma Sci 11:449–457 (2001).Google Scholar
- 42.M. Gibson. Product optimization. In M. Gibson (ed.), Pharmaceutical Preformulation and Formulation. Taylor & Francis, New York, 2001, pp. 295–330.Google Scholar
- 43.M. D. Tousey. The granulation process 101, basic technologies for tablet making. Pharm. Tech. Tableting and Granulation. 2002.Google Scholar
- 44.D. P. Petrides, A. Koulouris, and P. T. Lagonikos. The Role of process simulation in pharmaceutical process development and product commercialization. Pharm. Eng 22:1–8 (2002).Google Scholar
- 45.W. P. Ganzer, J. A. Materna, M. B. Mitchell, and L. K. Wall. Current thoughts on critical process parameters (CPP’s) and API Syntheses. Pharm Tech., July 2, 2005.Google Scholar
- 46.F. A. Menard. Quality by design in generic drug development. Presentation to FDA Office of Generic Drugs. September 25, 2006.Google Scholar
- 47.M. Glodek, S. Liebowitz, R. mcCarthy, G. McNally, C. Oksanen, T. Schultz, M. Sundararajan, R. Vorkapich, K. Vukovinsky, C. Watts, and G. Millili. Process robustness—A PQRI white paper. Pharm. Eng 26:1–11 (2006).Google Scholar
- 48.Rath and Strong. Design for six-sigma pocket guide. Rath and Strong Management Consutants/AON Management Consulting, Lexington, MA (2002).Google Scholar
- 49.C. Chen. Implementing quality by design: ONDQA initiatives. Advisory Committee for Pharmaceutical Science October 5, 2006. http://www.fda.gov/ohrms/dockets/ac/06/slides/2006–4241s1-index.htm (Accessed December 1, 2006).
- 50.National Institute for Pharmaceutical Technology and Education. Strategic roadmap for research and education. http://www.nipte.org. (2006).
- 51.Food and Drug Administration CDER. Guidance for industry, PAT—A framework for innovative pharmaceutical development, manufacturing, and quality assurance. September 2006.Google Scholar
- 53.C. Watts, and J. E. Clark. PAT: Driving the future of pharmaceutical quality. J. Pro. Ana. Tech 3(6):6–9 (2006).Google Scholar