The issuance of the new FDA Process Validation Guidance in January of this year is a significant event for several reasons. Fundamentally, the definition of what constitutes acceptable process validation differs dramatically from the conventional definition first put forth in the 1987 guidance. This guidance, more than any of the ICH documents or previous FDA guidance issued since the Critical Path Initiative in 2003, attempts to legislate the transformation envisioned by the agency. In 2004 the FDA issued its landmark FDA guidance Pharmaceutical cGMPs for the 21st Century— A Risk-Based Approach, which advocated a more scientific approach to demonstrating process quality. Since that time there have been many discussions regarding how to implement the principles of Quality by Design (QbD) and risk-based decision making. Few could argue that the adoption of these new principles has proceeded at glacial speed. There are many reasons the industry has been slow to embrace these new concepts, despite their potential benefits in terms of process predictability and business performance. The underlying challenge, beyond the development of organizational expertise and resource allocation, is the significant paradigm shift in compliance thinking.

Historically, the foundation of our industry’s compliance philosophy was based upon the three quality pillars of inspection, testing, and documentation, while the 2004 FDA guidance advocates a product quality philosophy based upon process understanding and the scientific application of risk to maximize the potential for predictable product performance. To do this, the industry found itself supplanting industry standard practice—and the three-validation-lot rule of thumb— with a more descriptive methodology that required the industry to design and defend its approach to process and product development. This new, descriptive approach requires a thorough understanding of statistics, probability, and risk. Even if the development team were equipped to meet this challenge, the compliance organization often found itself lacking the necessary linkage between the old philosophy and the new philosophy. Consequently, the concept of risk-based process validation meant adding rather than reducing risk to the compliance equation in the minds of most quality professionals.

So now the agency has drawn a line in the sand with its new process validation guidance. If compliance professionals are to make the transition to the new guidance, there will have to be a clear roadmap to articulate, in broad terms, the necessary quality attributes for each stage of the new guidance. I would advocate the following deliverables to ensure a clear compliance position as the process moves through the three stages of process validation.