A Case for Stage 3 Continued Process Verification

FDA Process Validation Guidance (Guidance for Industry: Process Validation- General Principles and Practices, Jan. 2011) outlines process validation activities in three stages – Stage 1: Process Design, Stage 2: Process Qualification and Stage 3: Continued Process Verification. Completion of Stage 2 subsequent to Stage 1 is a major milestone in the Process Validation Lifecycle as it confirms the process design and demonstrates the expected consistent performance of the manufacturing process. Knowledge and information gained from the design stage through the process qualification stage is used to complete this assessment. Stage 2 demonstrates suitability for successful commercial distribution where the data indicates that the process meets the conditions established in the protocol. Continued Process Verification is initiated for the subsequent commercial batches. Stage 3 assures that the process remains in a state of control during commercial manufacture.

21 CFR 211.180(e) regulations require evaluating and determining the need for change in manufacturing or control procedures on an ongoing basis. ICH Q8 (Rev 2) recommends an enhanced Quality by Design (QbD) approach that is comprised of a process validation lifecycle with a process verification stage. The March 2012 EMA Guidance on Process Validation requires continued process verification during commercial manufacture. This ensures a continued state of process control throughout commercial production.

Implementing Stage 3-Continued Process Verification makes business sense as it allows for freeing up of production lines and a higher throughput of the manufacturer’s portfolio. The ultimate result of a well-implemented Process Verification Process is an uninterrupted product supply that provides enhanced client service levels.