Process Validation: A Universal Concept in the Regulatory Landscape
Across the pharmaceutical, biopharmaceutical and medical device industries, process validation has historically been structured around the trilogy:
- Process Design: Develop and understand the process based on science, risk, and data (Stage 1)
- Process Qualification: Confirm the process performs as intended at scale, including qualification of equipment, facilities, utilities, and performance qualification (PPQ) (Stage 2)
- Continued Process Verification (CPV): Ongoing monitoring during routine production to ensure the process remains in a state of control (Stage 3)
These stages are interdependent, with no isolated checkpoints, and are foundational to an effective quality system.
However, there are some issues, as shown below for Stage 3 CPV:
- Data Overload: CPV systems generate massive datasets, making it hard to analyse without automation.
- Signal Detection: Differentiating between real trends vs. noise is statistically complex.
- Resource Allocation: Continuous monitoring needs skilled analysts and ongoing QA support.
- Global Consistency: Aligning CPV programs across multi-site/global manufacturing.
- Change Management: Integrating CPV findings into change control and improvement loops.
Why Move “Beyond the Trilogy”?
While the three-stage model remains the backbone of process validation, regulators worldwide now emphasise a lifecycle approach; one that treats process validation not as a one-time milestone, but as a continuous, data-driven assurance activity.
Whichever guidance/guideline document you comply with e.g. US FDA, EU, PIC/S, WHO etc, you will see the same underlying principles for a lifecycle approach but expressed slightly differently; the “language” differs, but the song is the same: prove your process works, keep it in a controlled/validated state, and document everything.
| Guidance / Guideline | Process Validation Expectation | Core Message |
| US FDA (2011 Guidance) | “Collection and evaluation of data, from the process design stage through commercial production, establishing scientific evidence that the process consistently delivers quality product.” | Prove the process works, keep monitoring. |
| EMA / EU Annex 15 | “Documented evidence that the process, operated within established parameters, performs effectively and reproducibly to produce a product meeting predetermined specifications and quality attributes.” | Document proof of consistency and compliance. |
| PIC/S (PE 009) | “Documented evidence providing a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality characteristics.” | Provide documented assurance of consistency. |
| WHO TRS 986 Annex 2 | “Demonstrate the manufacturing process is suitable for its intended purpose and capable of consistently yielding products of required quality.” | Show suitability and repeatable quality. |
The US FDA places stronger emphasis on statistical and science-based lifecycle control, and PIC/S/EMA often reference three consecutive successful PPQ batches as a standard (if supported by strong development data and risk assessments), but all are aligned on the lifecycle mindset.
The lifecycle approach responds to evolving industry and regulatory needs:
- Raw material and supplier variability impacting product quality.
- Process complexity in biologics and ATMPs where traditional validation is insufficient.
- Integration with Quality Risk Management (QRM) to focus on critical risks.
- Data-driven decision-making where CPV trends can trigger revalidation or improvement.
A lifecycle approach to validation is particularly relevant in the following applications:
| Industry | Example | Key Lifecycle Focus |
| Small Molecule Drugs |
Solid oral dosage manufacturing | Stage 3 trending for blend uniformity and dissolution |
| Biologics | Cell culture and purification | CPV to detect drift; Stage 1 defines critical parameters |
| Sterile Products | Aseptic fill-finish | Stage 2 PQ with media fills; Stage 3 EM/data trending |
| Advanced Therapeutic Medicinal Products | Cell and gene therapy | Adaptive validation for patient variability |
| CDMOs | Multiple client processes | Stage 2 DQ/PQ; flexible CPV |
| Combination Products | Drug-device interactions | Interface control and integration |
These areas demand a flexible, responsive approach to process validation—driven by data and rooted in process understanding.
Conclusion: Futureproofing with Lifecycle Thinking (Speaking the Same Language in Different Words)
The regulators message is the same: validation is a continuous journey, not a one-time event. The trilogy of design, qualification and verification remains, but lifecycle application turns it into a feedback loop where CPV informs design and qualification repeatedly.
- Lifecycle-based validation enables manufacturers to:
- Maintain a state of control through real-time data and trending
- Make faster, smarter decisions through continuous improvement
- Ensure robust, reproducible processes across scale and geography
By implementing the lifecycle approach, you create a globally resilient process validation strategy—one that speaks every regulator’s “language” while staying true to one universal principle: prove it works, keep it working, and never stop learning from the data.
Register for our webinar 15 October 2025 to learn more
Glossary
ATMPs – Advanced Therapy Medicinal Products
- Medicines for human use based on genes, cells, or tissue engineering.
CPV – Continued Process Verification
- Stage 3 of process validation; ongoing monitoring of process performance during routine production.
EMA – European Medicines Agency
- Regulatory authority for medicinal products in the European Union.
FDA – Food and Drug Administration
- US regulatory authority overseeing pharmaceuticals, biologics, and medical devices.
PPQ – Process Performance Qualification
- Part of Stage 2 process validation; confirms the process performs as intended at commercial scale.
PIC/S – Pharmaceutical Inspection Co-operation Scheme
- International co-operative arrangement between regulatory authorities for GMP harmonisation.
QRM – Quality Risk Management
- A systematic process for assessing, controlling, communicating, and reviewing risks to product quality.
WHO – World Health Organization
- United Nations agency providing global public health guidance, including GMP.
References
- US FDA – Guidance for Industry: Process Validation: General Principles and Practices (January 2011)
- European Medicines Agency (EMA) – EudraLex Volume 4, Annex 15: Qualification and Validation (2015)
- PIC/S – Guide to Good Manufacturing Practice for Medicinal Products (PE 009)
- WHO – Technical Report Series No. 986, Annex 2: WHO Good Manufacturing Practices: Main Principles for Pharmaceutical Products (2014)
- ICH – Q8(R2): Pharmaceutical Development
- ICH – Q9(R1): Quality Risk Management
- ICH – Q10: Pharmaceutical Quality System
- ICH – Q12: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management
- ISPE – Good Practice Guide: Process Validation Lifecycle
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