What if the quality of your sterile product depends on something as simple as complex as the way you clean?

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In pharmaceutical manufacturing, washing is a silent yet decisive process step, one that often determines whether sterility can truly be achieved. Every validated sterilization cycle and aseptic assembly begins with one essential condition: clean components.
Once seen as a preparatory task, cleaning has now become central to contamination control.
The revised EU GMP Annex 1 recognizes cleaning as a Critical Control Point within the Contamination Control Strategy (CCS): a process that must be designed, validated, and monitored with scientific precision.
At the heart of this transformation lies a timeless model: the Sinner’s Circle.
We have elevated it into a scientific compass for validated cleaning in sterile manufacturing. Its enduring insight is simple yet powerful: every cleaning action results from the balance of four forces: Time, Action, Chemistry, and Temperature (TACT).
By mastering this balance, at Fedegari we help manufacturers achieve consistent, verifiable cleaning that aligns with Annex 1 and PDA TR 29 principles, while laying the foundation for long-term efficiency and sustainability.

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From compliance to science.

Cleaning validation, once treated as a static compliance exercise, is now expected to be a scientifically designed, risk-managed process that evolves over its lifecycle. The shift from prescriptive testing to proactive science defines the current regulatory landscape.
Across all major regulatory frameworks, the same message emerges: cleaning is a critical process, one that directly influences the sterility and safety of your final product.

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EU GMP Annex 1 (2022) explicitly states that the cleaning of components and equipment used in sterile manufacturing must be validated and periodically requalified. The intent is to demonstrate consistent removal of residues (whether product, detergent, or microbial) ensuring that contamination sources within the Contamination Control Strategy (CCS) are kept under strict control. It moves beyond checklists and surface swabs toward a holistic, science-based approach that incorporates ongoing verification.
21 CFR 211.67 reinforces this same principle, requiring that equipment be cleaned, maintained, and sanitized at appropriate intervals to prevent contamination that could alter product quality or safety.
PDA Technical Report No. 29 builds on these expectations, framing cleaning validation as a lifecycle activity, comprising process design, qualification, and continuous verification. It emphasizes the identification of Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs) to ensure that every validated cleaning cycle remains consistent and under control in routine operation.

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From compliance to design: the Sinner’s Circle as the compass of cleaning

This evolution, from “prove it once” to “control it always”, turns
compliance into a true engineering discipline. And here’s where the Sinner’s Circle becomes your game changer: what if the real secret to clean surfaces isn’t just effort, but the exact energy needed?

In industrial cleaning, the Sinner’s Circle originally described how heat, chemistry, and mechanical energy could remove soil from fabrics.
In pharmaceutical manufacturing, its meaning deepens: it becomes the scientific grammar of validated cleaning.

These four variables, working together, determine whether a surface reaches its validated state of cleanliness.
They are no longer abstract factors: they are the Critical Process Parameters (CPPs) of washing.

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Time becomes the measurable exposure period that ensures contact between surfaces and detergent, including the dirty-hold time that determines how easily residues can be removed.

Action describes the mechanical energy applied by spray arms, flow, or turbulence inside automated washers, energy that must reach every internal surface, every joint, every bore.

Chemical concentration reflects the solvency, pH, and surfactant power of the detergent, optimized for soil type and controlled automatically through conductivity or dosing systems.

Temperature acts as a kinetic accelerator, increasing solubility and emulsification but requiring careful validation to avoid unwanted effects such as protein denaturation or corrosion.

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The scientific principle

Sinner’s Circle tells us what makes cleaning work, while the TACT balance explains how to make it reproducible. Each of the four variables (Time, Action, Chemistry, and Temperature) can be adjusted, but never in isolation. Together, they create a dynamic equilibrium that every validated process must understand, document, and control.This interdependence, rooted in the Sinner’s Circle, is what transforms cleaning into a controllable science, rather than a mere procedural habit. It is also what enables pharmaceutical engineers to design processes that are not only efficient and traceable but also defensible under regulatory scrutiny.

Engineering the circle: from design to critical parameters

When translated into pharmaceutical language, the TACT elements become Critical Process Parameters (CPPs), while their measurable outputs constitute the Critical Quality Attributes (CQAs) of the cleaning process.

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Optimization: when  sustainability meets compliance

Annex 1 and TR 29 both underline the need to design cleaning processes that are effective, efficient, and sustainable.
Optimization is therefore not optional; it is part of lifecycle control.
By fine-tuning the balance of TACT, engineers can reduce energy and water consumption while maintaining validated performance.

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These optimizations contribute to a facility’s ESG objectives while fulfilling Annex 1’s expectation of responsible utility management.
Efficiency is thus not a cost-cutting measure; it is a regulatory virtue, a sign that the process is scientifically understood and continuously improved.

Case studies: when theory becomes a level pro of reality


Every soil tells a story.
By manipulating the four TACT forces, cleaning engineers can adapt validated cycles to tackle even the most resistant residues.
Discover real success stories, straight from those who have experienced and tackled these challenges firsthand. Hear from experts who have made a real difference in the field.

 


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Don’t miss out on this rare opportunity.

Conclusion

In summary, industrial cleaning in the pharmaceutical sector isn’t just a simple preliminary task but a critical scientific discipline to ensure the sterility and safety of final products. The adoption of models like the Sinner’s Circle and the precise balancing of TACT parameters (Time, Action, Chemistry, Temperature) enables companies to optimize their cleaning processes, ensuring not only regulatory compliance but also long-term efficiency and sustainability.
While regulations such as Annex 1 and TR 29 establish guidelines for valid and continuous cleaning, it is essential that companies not only meet compliance requirements but also adopt a scientific approach that allows them to continuously evolve and optimize processes.

Looking ahead, innovation in cleaning process design, real-time monitoring, and the integration of more sustainable solutions will be key to tackling the challenges of modern pharmaceutical production. The adoption of advanced technologies and the intelligent application of the TACT model will further improve efficiency, reducing resource consumption without compromising quality.

 

 

Validated cleaning is therefore a matter of science, engineering, and continuous innovation, a goal that Fedegari supports with expertise, experience, and a forward-thinking vision.

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