The FDA Guidance for Industry “Process Validation: General Principles and Practices”, requires a new direction for Validation that is now a ''Life Cycle Process'' with 3 stages:
1. Process Design
2. Process Qualification
3. Continued Process Verification
The stage 3 “Continued Process Verification” is a new step in validation. Also legacy process should be (re)validated regarding this life cycle.
Continued process verification (CPV) as defined in the FDA process validation guideline helps bring quality management and compliance in the pharmaceutical industry to the next level, but it has been challenging to implement in practice.
The goal of this third validation stage is continual assurance that the process remains in a state of control (the validated state) during commercial manufacture.
Managing and reducing variation is at the heart of the FDA Process Validation Guidance. Clearly stated in the guidance is the need to understand variation, ability to detect variation, understand the impact of variation and ability to control variation.
The focus of CPV signals should always be to identify variation within specified limits defined in the control strategy. This applies when critical quality attributes (CQAs) are maintained within specifications and critical process parameters (CPPs) are maintained within proven acceptable ranges. Signals that are outside the control strategy (i.e., OOS) are investigated primarily within the quality management system (QMS).
Given that these signals are by definition within the specified limits defined in the control strategy, the risk inherent in disassociating the identification and reaction to signals from batch release is low, allowing for a more periodic review. The review frequency should be established with the monitoring plan.
At the completion of Stage 2— process performance qualification (PPQ) — a CPV plan shall be established.
The rationale can be risk based and should include an explanation of which process behaviors may merit further analysis.
During CPV plan execution, data is collected and analyzed at a predefined frequency by a cross-functional team (CFT) of subject matter experts (SMEs).
Any changes to control limits, signals, or processes that result from evaluation should be managed by the system most appropriate for the change (i.e., change control or CAPA). Quality approval is required to close out a response to signal for all three categories (escalation, evaluation, noaction).
 in Pharmaceutical Industry){kind=link}