2.2. FDA’s continous validation guideline supporting QbD

This guidance aligns process validation activities with a product lifecycle concept and with existing F.atDA guidance, including the International Conference on Harmonisation Guidance for industry, Q8(R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System.

The objective of this new guidance is to understand the sources of variation, detect the presence and degree of variation, understand the impact of variation on the process and ultimately on product attributes. The variation should be then controlled in a manner commensurate with the risk it represents to the process and product.³⁶

The validation approach is thus divided into the 3 phases of process design (includes building and capturing process knowhow and understanding), process qualification (includes the process performance qualification, protocol, protocol execution and report) and continued process verification. This last phase of continuous verification is completely new to the industry. This requires a continual assurance that the process remains in a state of control, while formerly execution and reporting of usually three validation batches as a one time event was considered sufficient to demonstrate process qualification. Therefore, now systems for detecting unplanned departures from the process as designed are essential to accomplish this goal throughout a product’s lifetime cycle.

³⁶ Guidance for Industry, Process Validation – General Principles and Practices; 2011