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Quality by Design (QbD) and Production System Fundamental Sigma Limits with a Pharmaceutical Industry Example Open Access

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Quality by Design (QbD) has been recognized as a superior manufacturing approach versus attempting to test in quality. Without designing for quality, the level of quality attainment (defect-free product) has been observed to plateau well short of six sigma, and efforts to further improve quality are met with diminishing returns on investment. This research quantitatively evaluates the phenomenon of a manufacturing sigma wall or quality plateau in the context of technological evolution, and demonstrates that QbD is superior to a quality by testing-centric model.The pharmaceutical industry, in which QbD is emerging as a recommended practice, is used as an example and case study in the research. Pharmaceutical development and manufacturing systems also rely on a Quality by Testing (QbT) model that uses release testing and other measures for assurance of quality. However, there is a significant gap between typical pharmaceutical production system capability (~ 2.5-3.5 sigma) and supplied quality (~ 5.16-5.6 sigma). To sustain high levels of product supply quality, the industry incurs a high cost of quality while retaining value at risk.The research confirms the gap between shipped pharmaceutical quality and production sigma. It also identifies systems-characteristic behavior (specifically the S-Curve technological evolution profile) that supports the use of systems theory and improvement tools. Finally, it performs a trade study to evaluate the extent to which QbD elements as expressed in contemporary literature eliminate production system contradictions (i.e. conflicts or unresolved trade-offs) needed to move to higher S-Curves and performance in comparison to the traditional model. The research also recommends additional QbD elements to minimize the effects of system contradictions.

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