Recommendations for Effective and Defendable Implementation of Quality by Design

Quality by Design (QbD) is a systematic, holistic, and proactive approach to development that begins with predefined objectives and emphasizes product and process understanding and process control based on sound science and quality risk management. In the past decade, an increasing number of pharmaceutical companies have been practicing QbD, enabling the successful development and scale-up of active pharmaceutical ingredient processes. QbD implementation is more complicated than desired in part because of the nonprescriptive nature of the QbD guidelines, which requires interpretation for the appropriate application of QbD, including regional regulations. In this paper, on the basis of observations made during two decades of QbD training and project support as well as frequently asked questions, certain practical recommendations are made regarding effective use of three QbD methods: risk analysis, statistical Design of Experiments, and scale-up investigations. Although QbD is still evolving, because of its business and technical benefits, including the definition of effective control strategies and the development of robust processes, the pharmaceutical industry is embracing the use of QbD elements while maintaining realistic expectations for the evaluation of QbD success.