Human and Cultural Factors in QbD - Risks and Opportunities

The principles of Quality by Design, including early definition of the factors that affect quality, and implementation of a quality management system, are well recognized as essential to predictability and profitability of any manufacturing process. Yet, are there elements of quality doctrine that have not been exploited to achieve quality and operational goals?

Much focus in QbD programs is given to the appropriate use of scientific methods to establish relationships between process factors and critical quality attributes, aligned with a system to monitor and manage these relationships. These activities, often pursued during development phases, are critical to ensure quality product. However, beyond this focus and timeframe lies substantial opportunity to maintain product quality and profitability, specifically through the recognition and management of longer term human interaction and cultural factors. And, the more abstract the process factors, the greater the need for proactive management of these human factors.

Biologics manufacturing presents a unique combination of challenges to maintaining control and reducing variability, including: production mechanisms that are complex, and often intangible, plus notoriously high measurement variability (both in-process and final product attributes). Hence, it is crucial that variability due to human interaction be continually understood and minimized, throughout the product lifecycle. A culture of systems thinking and continuous improvement is also demanded in this environment. Only then will changes in the process be promptly identified, and new knowledge shared between the functional (and often siloed) groups of early and late stage development, analytical, quality, commercialization, and operations.

The author describes the essential supplement of the lean manufacturing principles of standardized work, systems thinking, and continuous improvement to any QbD program to achieve operational goals. She provides examples in biologics manufacturing for the potential consequences when these principles are overlooked, and the benefits when they are deliberately managed.