Published on 07/12/2025
Understanding Routine, Periodic, and Change-Driven Revalidations in Pharma
Maintaining the validated state of pharmaceutical processes and systems is a regulatory imperative. Revalidation — whether routine, periodic, or change-triggered — ensures continued compliance, product quality, and patient safety throughout the lifecycle of a process or equipment. Revalidation is not just a formality; it is a fundamental requirement under FDA’s Process Validation guidance, EMA Annex 15, and ICH Q9.
This guide breaks down the three types of revalidation used in pharma — their purpose, regulatory expectations, how to determine when each applies, and step-by-step approaches for implementation.
1. What Is Revalidation in the Pharma Context?
Revalidation refers to repeated or periodic validation activities carried out to confirm that processes, equipment, or systems still perform as intended. It applies to cleaning procedures, manufacturing processes, analytical methods, utility systems, and computerized systems. Revalidation ensures that the system remains in a state of control under GMP-compliant conditions.
According to EMA Annex 15:
“Revalidation should be performed when there is a significant change to the process, equipment, or any other critical parameter which may affect product quality.”
Revalidation is an integral part of Stage 3 of
2. Types of Revalidation
The types of revalidation in pharmaceutical environments can be broadly categorized into three classes:
- Routine Revalidation — Scheduled based on predefined intervals.
- Periodic Revalidation — Conducted based on risk, data, or trends observed over time.
- Change-Triggered Revalidation — Initiated in response to specific changes affecting validated state.
2.1 Routine Revalidation
Routine revalidation is planned in advance, typically on a fixed timeline (e.g., every 3 years), regardless of whether changes or deviations have occurred.
Examples:
- Annual cleaning validation for multi-product equipment
- Triennial requalification of HVAC systems
Documentation Required:
- Approved revalidation protocol
- Historical performance data summary
- Executed testing with sample results
- Final report with conclusions and CAPAs if applicable
2.2 Periodic Revalidation
Periodic revalidation is not based on a calendar, but instead on trends, risk, and operational data collected during Continued Process Verification (CPV). This approach is in line with lifecycle validation concepts.
Examples:
- Revalidation of a stable process based on 2-year CPV trend analysis showing drift
- Re-qualification of lab instruments due to equipment utilization anomalies
Triggers:
- OOS or trending deviations
- High variability in critical process parameters (CPPs)
- Negative audit findings
2.3 Change-Triggered Revalidation
This is the most common type of revalidation and is initiated when a validated system is modified. Regulatory authorities expect that every change be assessed for its potential impact and appropriate revalidation planned.
Triggers:
- Change in raw material vendor or grade
- Equipment upgrades or replacements
- Process parameter revisions (e.g., mixing speed, temperature)
- Facility layout changes
Linked Systems: Change control, CAPA, deviation management.
Refer to regulatory documentation best practices for how to incorporate change control impact assessments.
3. Regulatory Expectations
FDA: Expects risk-based, documented revalidation as part of lifecycle process validation.
EMA: Annex 15 mandates periodic revalidation and evaluation post-change.
WHO: Technical Report Series No. 1019 emphasizes validation review based on equipment usage and process performance.
All authorities agree that revalidation should be supported by justification, be documented, and follow Good Documentation Practices (GDP).
4. Sample Revalidation Frequency Matrix
| System/Process | Type of Revalidation | Frequency | Trigger |
|---|---|---|---|
| Tablet Compression | Routine | Every 3 years | Time-based |
| Purified Water System | Periodic | Every 2 years or based on trend | CPV trend drift |
| Coating Process | Change-triggered | As needed | New coating machine installed |
| Cleaning Process | Routine | Annually | Multi-product risk |
5. Risk-Based Revalidation Approach
Modern validation strategies apply risk management tools such as:
- FMEA (Failure Mode and Effects Analysis)
- Risk Ranking and Filtering
- Fishbone Diagrams for Root Cause Analysis
Use these tools to determine whether revalidation is necessary and to what extent.
For example, if the risk score for a cleaning procedure increases due to a change in API potency, the cleaning process must be revalidated.
6. Integration with Change Control & CAPA
Revalidation must be tightly integrated with change control procedures. Every change should include a validation impact assessment (VIA) to determine whether:
- No revalidation is required (low risk)
- Partial revalidation is sufficient (medium risk)
- Full revalidation is mandatory (high risk)
CAPAs from deviations or complaints may also necessitate revalidation. These are typically managed via a deviation or CAPA tracking system linked to validation records.
7. Documentation Requirements
- Revalidation protocol (clearly stating type: routine/periodic/change-triggered)
- Justification memo or risk assessment
- Approval by QA and Validation Head
- Raw data and executed test sheets
- Summary report with conclusion and any CAPAs
Ensure all documents follow GDP-compliant SOPs and are archived securely.
8. Common Audit Findings
- Revalidation overdue or skipped
- Change implemented without impact assessment
- Lack of justification for extended revalidation frequency
- CAPA closed without linked revalidation
Maintain a revalidation tracker that includes dates, reasons, outcomes, and status of each item.
Conclusion
Revalidation is not optional — it’s a core requirement to ensure that validated states are preserved over time and in the face of change. By defining a risk-based, structured, and timely revalidation strategy — and linking it with CPV, change control, and CAPA — pharmaceutical manufacturers can remain inspection-ready and ensure ongoing product quality.
Whether routine, periodic, or change-triggered, revalidation should be proactive, documented, and embedded in your validation lifecycle program.