There can be no doubt that the last decade for the pharmaceutical and biotech industry has been full of extraordinary change. Regulatory changes culminating in the FDA’s 2004 guidance A Risk-based Approach to CGMPs underscored the reality that as an industry we needed to evolve. In the U.S., the FDA has undergone an unprecedented transformation in an effort to shed its overhead-intensive compliance baggage and move the industry toward more effective product development. The recognition that change is essential is not limited to the FDA. There has been a global push to drive toward an asset of rules and standards that represent a balanced summation of what we consider reasonable best practice. The International Committee for Harmonization (ICH) developed its portfolio of standards; culling input from the world’s best and brightest in terms of pharmaceutical product development. There is universal agreement that the ICH guidelines Q7, Q8, Q9, and Q10 set the standard from a product development and compliance perspective for competing in the western markets of the U.S. and Europe.

This has been a long and arduous journey for the industry and we are by no means nearing its completion. As a Lean Six Sigma Master Black belt, I understand all too well the importance and challenges associated with changing organizational thinking. The FDA recognized this first in examining their own ability to evaluate the risk benefit profiles of new therapies being brought to market, and second in examining the industry’s ability to defend its own work. Mired in regulatory overhead, the cost benefit ratio of bringing new therapies to the marketplace was drifting south. As costs escalated and the agency’s aversion to risk reached new heights, the pharmaceutical industry found itself with longer and longer development timelines to market. This may have not been apparent when looking at NDA review times, but when extended to IND and ANDA cycle times the trend was unmistakable. Clearly it was time for a paradigm shift.

Further complicating this situation is the changing market landscape. The growth of the drug delivery market in the U.S. has changed the technical and regulatory landscape significantly. In looking at the overall drug delivery market in the U.S., the forecasted market size in 2009 is estimated at approximately $80 billion escalating to over $150 billion by 2011. In the current market, over 50% of the market is dominated by modified release, implants, and transdermal systems with the majority share belonging to modified release delivery systems. Changing market dynamics, patent extension strategies, and technology innovations will have a profound impact on where the demand is in the marketplace. It is forecasted that the market is going to shift to a new emphasis on targeted drug therapies. The evolution of PEGylation, nanotechnology along with polymer and liposome technology solutions, is expected to comprise almost 50% of the overall U.S. market by 2011.¹

This convergence between CFR 820 regulatory world and the CFR 210/211 world presents unique challenges for development, compliance, and regulatory organizations. The roadmaps are similar philosophically but the milestones and metrics are very different. This convergence has been aided to some extent by the adoption of Six Sigma² and Lean Manufacturing programs within the manufacturing environment. The motivation for this diversion has been driven by both a need to comply with the new regulations emphasizing Quality by Design, and partially by the need to improve and maintain business performance. The industry’s infatuation with operational excellence has been tenuous. Big Pharma and biotech along with large medical device and diagnostic companies have made the investment in operational excellence principles, particularly on the factory floor, but have been slow to move these principles to the product design phase.