Why "Re-Validation" is Just a Band-Aid: Solving Process Validation Deviations for Good

In the GMP world, Process Validation (PV) is often treated as the "final boss" before market launch. When a deviation occurs during a PV batch, panic usually sets in. The timeline is at risk, management is breathing down your neck, and Quality Assurance (QA) often falls back on the reflexive "re-validation" of three more batches. But let’s be blunt: if you just run three new batches without fixing the fundamental issue, you aren't building a sustainable system; you are simply slapping an expensive band-aid on a structural fracture.

The Regulatory Anchor The requirements for handling validation deviations are non-negotiable under EU GMP Annex 15:

Any results that fail to meet pre-defined acceptance criteria must be recorded as a deviation and fully investigated. Process validation must establish whether all quality attributes and process parameters considered important for ensuring a validated state can be consistently met.

Annex 16 dictates that the Qualified Person (QP) must ensure all investigations pertaining to the batch—including Out of Specification (OOS) and Out of Trend (OOT) investigations—have been completed to a sufficient level to support certification.

The Reality Check: Why Standard SOPs Fail In practice, we often see the "Validation-by-Repetition" syndrome. When a PV batch fails, the cause is quickly labeled as "human error" or a "one-time equipment glitch."

The problem: Standard SOPs are typically designed for reactive troubleshooting in routine production. In the validation phase, however, a deviation is a symptom of poor process understanding or a weak control strategy. If you act superficially here, you risk an unstable process during the commercial phase—which is far more expensive to fix later. "Human error" should be justified only after ensuring that procedural or system-based errors were not overlooked.

The Practical Methodology: The HOW before the WHAT When PV hits a wall, you don’t need panic; you need an analytical framework:

A. Initial Evaluation (Impact Assessment) Stop asking "Can we save this batch?" and start asking "What does this failure tell us about our process model?"

Scientific Basis: Evaluate the deviation against your Design Space (if established) and the correlation between Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs). Risk-Based Approach: Use Quality Risk Management principles to determine if the failure is systemic or truly isolated.

B. Investigation Structure A validation failure is an invitation to perform a deep-dive technical audit.

Qualified State: Was the equipment truly in its qualified state during the run? Variability: Identify sources of variation. Are your raw material specifications tight enough? Data Integrity: Critically review raw data for inconsistencies that might have been missed in earlier development.

C. QP Involvement The QP may consider certifying a batch with an unexpected deviation only if:

Registered specifications are met. The potential impact on quality, safety, or efficacy is concluded to be negligible. The root cause has been thoroughly investigated and corrected. For biological products: Exercise extreme caution, as deviations from approved processes can have unpredictable impacts on safety and efficacy.

Transfer Knowledge: Sustainable Stability over One-Time Success To avoid the "re-validation trap" in the future, QA and Management must shift their mindset:

Move Beyond the "Rule of Three": Embrace Ongoing Process Verification throughout the product lifecycle. PV doesn't end with the third batch; it is a lifecycle commitment to monitoring process capability. Data Ownership: The internal team must own the statistical process control. Do not rely solely on external consultants to write your reports. The knowledge of process capability must stay in-house. Early Warning Systems: Implement robust monitoring and trending before you reach the PV stage to minimize surprises during validation.

My tip for Management: A stopped and thoroughly investigated PV is significantly more valuable than a "pushed through" one. The cost of recalls or supply shortages due to unstable processes dwarfs the cost of sound process development every single time.