![]() It enhances the manufacturer’s ability to identify the root causes of manufacturing failures. Furthermore, it transfers resources from a downstream corrective mode to an upstream proactive mode. As such, it enhances development capability, speed, and formulation design. QbD uses a systematic approach to product design and development. After regulatory approval, effort should continue to improve the process to reduce product variability, defects, rejections, and recalls. In addition, an improved product and process understanding can facilitate the identification and control of factors influencing the drug product quality. Achieving this objective requires robustly designed product and process. The second objective of pharmaceutical QbD is to increase process capability and reduce product variability that often leads to product defects, rejections, and recalls. Nonetheless, it should be recognized that ICH documents ( 3– 9) did not explicitly acknowledge clinical performance-based specifications as a QbD goal, although this was recognized in a recent scientific paper ( 10). The recent FDA discussions on the assayed potency limits for narrow therapeutic index drugs and physical attributes of generic drug products reflect this trend ( 16). Some examples of FDA policies include tablet scoring and bead sizes in capsules labeled for sprinkle ( 14, 15). Since the initiation of pharmaceutical QbD, the FDA has made significant progress in achieving the first objective: performance-based quality specifications. Under QbD, these goals can often be achieved by linking product quality to the desired clinical performance and then designing a robust formulation and manufacturing process to consistently deliver the desired product quality. To enhance root cause analysis and postapproval change management This paper is intended to describe the objectives of pharmaceutical QbD, detail its concept and elements, and explain implementation tools and studies. There is confusion among industry scientists, academicians, and regulators despite recent publications ( 10– 13). Nonetheless, many implementation details are not discussed in these guidances or documents. These documents provide high level directions with respect to the scope and definition of QbD as it applies to the pharmaceutical industry. In addition, the ICH Q1WG on Q8, Q9, and Q10 Questions and Answers the ICH Q8/Q9/Q10 Points to Consider document and ICH Q11 (Development and Manufacture of Drug Substance) have been issued, as have the conclusions of FDA-EMA’s parallel assessment of Quality-By-Design elements of marketing applications ( 6– 9). ![]() Over the years, pharmaceutical QbD has evolved with the issuance of ICH Q8 (R2) (Pharmaceutical Development), ICH Q9 (Quality Risk Management), and ICH Q10 (Pharmaceutical Quality System) ( 3– 5). FDA’s emphasis on QbD began with the recognition that increased testing does not necessarily improve product quality. ![]() The US Food and Drug Administration (FDA) encourages risk-based approaches and the adoption of QbD principles in drug product development, manufacturing, and regulation. Woodcock ( 2) defined a high-quality drug product as a product free of contamination and reliably delivering the therapeutic benefit promised in the label to the consumer. Juran believed that quality should be designed into a product, and that most quality crises and problems relate to the way in which a product was designed in the first place. Quality by design (QbD) is a concept first developed by the quality pioneer Dr. This understanding will facilitate better communication between those involved in risk-based drug development and drug application review. As the pharmaceutical industry moves toward the implementation of pharmaceutical QbD, a common terminology, understanding of concepts and expectations are necessary. QbD tools and studies include prior knowledge, risk assessment, mechanistic models, design of experiments (DoE) and data analysis, and process analytical technology (PAT). 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. This review further clarifies the concept of pharmaceutical quality by design (QbD) and describes its objectives. ![]()
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