This article is part of a special issue on Outsourcing Resources
Quality by design (QbD) is a concept that promulgates a core message that quality should be built into a product based on
knowledge of its characteristics and understanding of the process by which the product is manufactured. In a nutshell, QbD
is about communicating meaningful and relevant science upfront to establish postregulatory approval opportunities that will
guide subsequent manufacturing improvements. QbD speaks to real and significant changes in how industry and regulatory agencies
approach the regulatory process.
Origins of QbD
Any discussion of QbD should be framed in the context of the industry and regulatory climate at the time that FDA introduced
the QbD concept as part of its two-year initiative, Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach Pharmaceutical cGMP initiative (also referred to as the Pharmaceutical cGMP Initiative or 21st Century Initiative) in 2002. QbD is not a new concept from
a pharmaceutical technology perspective. It is, however, a new concept relative to pharmaceutical regulatory review and submission.
As a systematic and prospective approach to product design, process design and control, process performance, and continuous
improvement, QbD designs quality into the manufacturing process. By doing so, QbD encourages innovation, continuous quality
improvement, and science- and risk-based regulatory processes and ensures the availability of high quality medicines to the
Before the Pharmaceutical cGMP Initiative, the pharmaceutical industry already had begun moving toward conveying a more science-based
approach through its emphasis on collaboration and risk-based regulation; the Pharmaceutical cGMP Initiative significantly
hastened that process. Then, as now, the industry as a whole was doing a great deal of innovative work, but neither industry
nor FDA were structured to encourage knowledge sharing. By focusing on what the regulatory agencies wanted, pharmaceutical
companies limited their risk of regulatory exposure, but they also limited the vital, cross-industry knowledge sharing that
advances industries and positions them for continued growth.
Because the orientation of regulatory authorities did not encourage quality to be built into the design of the pharmaceutical
manufacturing process, multiple and repetitive inspections were the means by which quality was measured and demonstrated.
This quality-by-analysis method of monitoring drug-product safety and efficacy brought reliable pharmaceuticals to market
but required manufacturers to notify FDA of any change to quality or to the current manufacturing process. Depending on the
change, time-consuming and costly requalification and subsequent regulatory approval might be required.
Focusing on the regulation of drug-product quality, the initiative, Pharmaceutical cGMPs for the 21st Century: A Risk-Based
Approach (subsequently renamed Pharmaceutical Quality for the 21st Century) was intended to modernize FDA regulation of pharmaceutical
quality for veterinary and human drugs and for human biological products such as vaccines. The goals of the initiative were
to ensure that regulatory review, compliance, and inspection policies are based on pharmaceutical science and to foster the
rapid adoption of technological advances throughout the pharmaceutical industry. Under any name, the ambitious initiative
seeks to demonstrate and provide examples of enhanced quality.