Building a Framework for Quality by Design - Pharmaceutical Technology

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Building a Framework for Quality by Design
The author describes the framework needed to implement QbD and achieve the deeper process understanding that is fundamental to QbD.

Pharmaceutical Technology
Volume 33, Issue 10

Process and product robustness

Process and product robustness are critiommunicationsInc.2007cal to the performance of the process over time. Design space should incorporate the results of robustness experiments. In general terms, robust means that the performance of the entity is not affected by the uncontrolled variation it encounters. Accordingly, a product is robust if its performance is not affected by uncontrolled variations in raw materials, manufacture, distribution, use, and disposal (15). Examples of robust products are user-friendly software and pharmaceuticals that have no side effects regardless of how or when they are administered.

A process is robust if its performance is not affected by uncontrolled variation in process inputs, process variables, and environmental variables. Robust processes are those processes that perform well when faced by large variations in raw-material characteristics and differences in ambient conditions and operating teams.

QbD changes

Using QbD creates a paradigm shift from the usual approach to development (16). QbD thus represents a cultural change that must be addressed with change-management techniques such as the eight-stage change model developed by Kotter and associated change-management tools (17–18). The importance of change management is not recognized by many organizations that deploy QbD and other improvement techniques. As a result, the promise of the associated change initiative is seldom realized even in minor terms.


As shown in other industries and more recently in the pharmaceutical industry, QbD is an effective method for developing new products and processes. QbD enables effective technology transfer and the optimization and improvement of existing processes. QbD works because it fosters process understanding that is fundamental to the creation of the design and control spaces and to sustain performance. The design space is critical to the success of QbD because it produces the following: performance on target and within specification at minimal cost with fewer defective batches and deviations; greater flexibility in process operation; and the ability to optimize manufacturing operations without facing additional regulatory filings or scrutiny. This process understanding enables the reduction of process variation and the creation of process-control systems that are based on sound science and quality risk-management systems.

QbD works beyond development and manufacturing to include functions such as technology transfer, change control, deviation reduction, and analytical methods development and improvement. All work is a process, and QbD is an effective method for improving processes. QbD s use will no doubt broaden in the future, and its application in the life sciences is almost without bounds.

Ronald D. Snee, PhD, is president of Snee Associates, 10 Creek Crossing, Newark, DE, 19711 tel: 610.213.5595, fax 302.369.9971,


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