In recent decades the pharmaceutical industry has used innovative, cutting edge technology to research and develop new drugs of immense value to society. By comparison there has been relatively little emphasis on processing, so these products tend to be manufactured using empirically developed, relatively inefficient, batch processes. The advent of Quality by Design (QbD) and the Process Analytical Technology (PAT) initiative invites the industry to use its considerable skills to address this imbalance, and transform process operation and efficiency.
One of the keys to this transformation will be a better understanding of powders since almost all pharma products are handled in this form at some point during manufacture. Modern powder characterisation methods have an important role to play providing data that can used to convert process- or product-specific experience into more fundamental knowledge.
ICH (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use) Guideline Q8: Pharmaceutical Development describes the principles of QbD. It suggests that the industry should switch from an approach that checks for quality by testing, to one that designs quality into the product and manufacturing process. PAT is a Food and Drug Administration (FDA) initiative designed to facilitate the uptake of new analytical technologies. Its aim is to reduce the regulatory burdens that restrict innovation in the processing arena to encourage improvements in efficiency.
The underlying message of both QbD and PAT is that the industry needs to improve understanding and adopt a knowledge-based approach to product and process optimisation. QbD and PAT are symbiotic rather than distinct. QbD encourages better understanding of the process at an early stage and the identification of critical process parameters, those that should be closely monitored and controlled. Relevant analytical technologies optimise information gathering during the pilot stage, and enhance understanding throughout the manufacturing life cycle, augmenting the knowledge base.
But neither QbD nor PAT is a regulatory requirement so why should anyone embrace this new way of working? The simplest answer is that the old ways are not sustainable. The pharma industry needs to bring new products to market successfully and quickly recoup the growing costs of development. Understanding the product and process may involve additional investment in the early stages, but ultimately it accelerates time to market and improves the reliability of scale-up. It also optimises process efficiency, increasing profitability, particularly when patents expire and the growing generics industry exerts intense commercial pressure.
Changes in regulatory approach also provide an incentive. From necessity the regulators now have to adopt a risk-based approach, focusing their efforts on products and processes that have the greatest potential for harm. Companies who use QbD and PAT to manufacture products with well-defined performance, using clearly understood processes will therefore ultimately be subjected to a lighter regulatory touch.
So there are good reasons for change but it will require better fundamental knowledge and much improved understanding. The industry will need to adopt new ways of working and new tools to access the information it requires.
(As seen in the 7/22/08 edition of the Pharmaceutical Online www.pharmaceuticalonline.comnewsletter)