ABSTRACT
Process validation is a regulatory requirement, and the traditional approach to process validation was a compliance-driven event. Success of process validation was characterized by a demonstration that the process is capable of producing three consecutive, commercial-scale batches that meet quality standards. This approach uses little product and process knowledge to identify critical quality attributes (CQAs). As a result, the process performance characteristics chosen for validation may not be truly indicative of product quality. In addition, even if the three-batch validation study is successful, the chance for future batches to meet acceptance limits remains unknown. In January 2011, the Food and Drug Administration (FDA) published updated guidance FDA Guidance for Industry on Process Validation: General Principles and Practices (FDA 2011). The guidance places a great deal of emphasis on process design and process control during commercial manufacturing. It stresses that process validation is not a one-time event, but an ongoing program. Process validation is defined as “the collection and evaluation of data, from the process design through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality.” The guidance aligns process validation activities with a product life cycle and risk-based paradigm, as well as with other existing guidelines, including ICH Q8(R2) Pharmaceutical Development (ICH 2006), ICH Q9 Quality Risk Management (ICH 2007a), ICH Q10 Pharmaceutical Quality Systems (ICH 2007b), and ICH Q11 Concept Paper (ICH 2011). It represents a significant shift of regulatory requirements from the traditional “test to compliance” approach using one experiment to the “quality by design” approach throughout the life cycle of the product and process. It ushers in a science and risk-based development paradigm that yields product quality through process design and control. The new guidance approaches process validation in three stages:
• Stage 1-Process Design (PD): The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale-up activities.
