As in the old fable of the blind men touching different parts of an elephant and then producing conflicting accounts, misconceptions about the nature of Quality by Design (QbD) add up to a fragmented understanding. A part is taken for the whole, and the unity that permeates all of the parts – the elephant in its entirety – remains unseen.

To put it simply, QbD is about focusing on the product and the patient from the outset. Understanding the quality risks of a pharmaceutical product to the patients - and then systematically tracing back into what is critical. Initially, what is critical about the product and then what is critical in the raw materials and in the manufacturing processes.

There is a clear tendency in the pharmaceutical industry towards using QbD to develop medicines in a much smarter and cost-effective way. But QbD is not only about development – it has far wider applications.

The main reason for the industry’s sluggishness in implementing QbD is regulatory fear, i.e. the risk of not getting the product approved by the health regulating authorities. But the fact is that the industry itself is responsible for the bottleneck. The regulators in the US Food and Drug Administration (FDA) and the European Medicines Agency have often expressed their dismay at how slow the industry is to adopt QbD.

Since the FDA in 2004 released ‘Process Analytical Technology (PAT) - A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance’, its significance to the industry has been discussed.

QbD is not only an integral part of PAT but in fact subsumes PAT under the larger principle of designed-in quality. Further, the FDA made it clear from the beginning that the goal of PAT is not the technological automation of process control, but comprehensive process understanding. As the PAT guidance says, “a process is generally considered well understood when all critical sources of variability are identified and explained; variability is managed by the process; and, product quality attributes can be accurately and reliably predicted over the design space established for materials used, process parameters, manufacturing, environmental, and other conditions.”

Because the PAT initiative and the concept of designed-in quality appeared at first to be focused on drug development, the misconception arose that QbD was also primarily for use in developing drugs and the manufacturing processes that would be used to produce them. But the FDA also encouraged improved process understanding and continuous improvement of manufacturing processes for products already in the market.

QbD applies to all phases of the product life cycle: drug development, scale-up, manufacturing of both new and in-market products and technology transfer of processes and products to other sites. In drug development, for example, the potential of design space understanding leading to robust manufacturing processes is perhaps the most widely understood aspect of QbD. But QbD offers a further advantage here. Because development usually takes placeover a long period of time and often involves many people, it can sometimes result in misunderstandings, errors, and redundant activity. QbD keeps an understanding of design space at the forefront of development efforts, providing the coherence and continuity that trial-and-error approaches lack. QbD can also help maintain ‘lifetime development’ – the continued gathering of data after a product is already in production. Because only a limited amount of data accumulates during initial development, additional data, framed by the product’s design space, can be helpful in deepening process understanding and continually improving the process.

In January 2011, the FDA published a new guideline on process validation that builds on many of the concepts of QbD. It is already being enforced by FDA investigators during inspections. However, with or without the new process validation requirements, QbD is a new manufacturing paradigm in the pharmaceutical industry. But when we strip away all the hype and slang, we see that the concept has been around in other industries for many years.

Other industries have done it without any regulatory involvement, simply because it makes good business sense. So when an article in The Wall Street Journal in 2003 claimed that “The pharmaceutical industry has a little secret: its quality principles lag behind those of laundry soap or potato chip manufacturers”, it was a sign that the world was about to change. Today many of the business benefits that these industries have enjoyed for years are becoming available to pharmaceutical companies. QbD is here. It is time for the industry to remove the blinkers.

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You can find more articles related to QbD in our Angle magazine on the topic.