WHAT DOES QbD MEAN?
Depending on whom you talk to, you will get different descriptions of what QbD is. Some see it as a product approval quid pro quo to raise the regulatory compliance bar or the latest flavor-of-the-month that adds bureaucracy, cost, and time to product development. All QbD really means, however, is that products, and the processes that make them, are designed in advance to meet their product quality specifications and process control requirements.
These techniques are suspected of taking too much time and costing too much compared with the traditional trial-and-error methods that have been prevalent in development. But a better approach is to structure an experimental design that optimizes the available development time and project funds while maximizing the product and process data delivered. If this sounds too good to be true, consider that design of experiments (DOE), the heart of QbD, offers returns that are four to eight times greater than the cost of running the experiments in a fraction of the time that it would take to run one-factor-at-a-time experiments. (See box on DOE). Furthermore, these approaches are the only way to unlock interactions of multiple factors, something trial-and-error and one-factor-at-a-time experiments cannot. When the QbD approach is used, products are purer and more potent and processes are more robust and have higher productivity. Also, technology transfer risks are reduced because fewer start-up runs and less start-up time are needed, which can lower start-up costs and speed the time-to-market.
If the traditional approach is ok, why should we be concerned with cost and productivity? Companies, governments, and health maintenance organizations (HMOs) face conflicting budget priorities, expanding demand, and higher costs per person for healthcare. Product cost and the cost of quality and compliance are under increasing pressure to be justified or reduced. In short, improved quality, higher productivity, lower cost, and improved compliance are the roadmap for the future. These goals can be achieved with QbD application. Neway has efficiently made the business case for QbD.1
CONVERTING THE SKEPTICS
Activities like QbD and process analytical technology (PAT) have been standard practice at chemical companies since the mid 1950s. These companies embraced these approaches because it saved them large amounts of money and time. But chemical companies, of course, are not regulated the way the pharmaceutical industry is. Our regulations create a different environment, and we must adapt to that difference. Validation presents the most obvious constraint.