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Final Process Validation Guidance Confirms FDA’s Move to Risk-Based Approach

More than two years after the draft was initially issued, FDA has finalized the much anticipated Guidance for Industry Process Validation: General Principles and Practices, confirming the agency’s effort to take a more modern risk-based approach to validation.


While there are no surprises in the final guidance, the most significant change from the initial draft is the welcome elimination of the requirement that viral clearance and impurity removal studies be conducted under full cGMP conditions. Instead, the guidance requires quality unit oversight of these studies regardless of the scale at which they are performed to ensure adherence to sound scientific methods and principles and that all conclusions are supported by the data. Industry pushed hard for this change to align the new guidance with ICH Q5A and Q10, and European guideline CPMP/BWP/268/95.

As with these other guidelines, FDA’s final guidance focuses on a risk-based approach and does not include specific recommendations. For instance, those expecting it to specify a number of process performance qualification batches required for licensure will undoubtedly be disappointed. Despite industry requests for clarification on this point, the guidance recommends the use of risk-based decision making during performance qualification to assess process consistency, and acknowledges that risk management tools should be used during all stages of process validation. While many would have liked to see FDA endorse the de facto standard of “three consecutive batches” for process performance qualification, the agency’s decision to leave this out allows companies flexibility in interpreting this requirement. If process validation work conducted during the Design phase is done properly, three process performance qualification batches should be sufficient to demonstrate process consistency. Expanded characterization and sampling during the Verification stage further reduces the risk of this approach.

The new guidance confirms the evolution of process validation from a one-time activity performed just prior to regulatory submissions to a lifecycle activity that begins early in development and continues long after commercialization. According to FDA, the guidance “…encourages the use of modern pharmaceutical development concepts, quality risk management, and quality systems at all stages of the manufacturing process lifecycle…,” an approach that has been used for decades in other industries to improve product quality, lower costs, and decrease time to market. It is now time for the biopharmaceutical industry to embrace and implement these concepts to improve their drug development process and decrease regulatory risk.


Blog article by: James Blackwell, Patti Seymour, and Howard Levine