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Understanding Pharmaceutical Quality by Design

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Abstract

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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Acknowledgment

The authors would like to thank Lane V. Christensen, Devinder Gill, Frank Holcombe Jr, Robert Iser, Khalid Khan, Robert Lionberger, Jennifer Maguire, Christine Moore, Yingxu (Daniel) Peng, Andre Raw, Bhagwant Rege, Susan Rosencrance, Vilayat Sayeed, Paul Schwartz, Glen Smith, Yue (Helen) Teng, Youmin Wang, Huiquan Wu, Abhay Gupta, Ziyaur Rahman, and Naiqi Ya for their valuable suggestions.

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Authors and Affiliations

  1. Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993, USA

    Lawrence X. Yu, Mansoor A. Khan & Janet Woodcock

  2. University of Michigan, Ann Arbor, Michigan, 48109, USA

    Gregory Amidon

  3. University of Maryland, Baltimore, Maryland, 21201, USA

    Stephen W. Hoag & James Polli

  4. Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    G. K. Raju

  5. Light Pharm Inc., Cambridge, Massachusetts, 02142, USA

    G. K. Raju

Authors
  1. Lawrence X. Yu
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  2. Gregory Amidon
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  3. Mansoor A. Khan
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  4. Stephen W. Hoag
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  5. James Polli
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  6. G. K. Raju
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  7. Janet Woodcock
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Correspondence to Lawrence X. Yu.

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Yu, L.X., Amidon, G., Khan, M.A. et al. Understanding Pharmaceutical Quality by Design. AAPS J 16, 771–783 (2014). https://doi.org/10.1208/s12248-014-9598-3

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  • DOI: https://doi.org/10.1208/s12248-014-9598-3

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