In the pharmaceutical industry, Good Manufacturing Practices (GMP) globallyclassify cleanrooms into four levels (A, B, C, and D) based on varying process risks. This constitutes a tiered, layered system for controlling microorganisms and particulates. Air filtration systems are crucial engineering guarantees for achieving and maintaining this system.
I. Cleanliness Classification of Pharmaceutical Cleanrooms
The classification of pharmaceutical cleanrooms directly corresponds to different process risks and protection requirements. From high-risk aseptic operations to lower-risk auxiliary production, each level has its unique design logic.
Level A Area (High-Risk Core Area): This is the most critical area in aseptic drug production, typically referring to high-risk operation points such as filling, exposed stoppers, and open containers. It requires a dynamic, unidirectional (laminar) air environment, where air flows unidirectionally at a uniform cross-sectional velocity (typically 0.36-0.54 m/s) to rapidly remove particles generated during operations, achieving immediate contamination control. Its background environment is typically a Class B zone.
Class B Zone (High-Risk Background Zone): As the static background environment of the Class A zone, the Class B zone also requires extremely high cleanliness. It provides a high-quality clean air “protective shield” for the Class A zone and accommodates critical auxiliary operations such as personnel changing clothes and aseptic connections. The Class B zone typically uses non-unidirectional flow (turbulent flow), but with an extremely high air exchange rate to maintain the overall cleanliness of the environment.
Class C and D Zones (Medium/Low-Risk Zones): These two levels are used for non-aseptic operation stages in the production of sterile pharmaceuticals (such as solution preparation, storage after instrument cleaning and sterilization), and the production of non-sterile preparations. Their cleanliness requirements decrease progressively, employing non-unidirectional flow and maintaining a room pressure gradient through reasonable supply and return air design to prevent cross-contamination.
II. Classification and Configuration Strategy of Air Filtration Systems
Grade A:High-risk aseptic operating points require instantaneous contamination removal and unidirectional flow protection. ULPA filters (e.g., ISO 45 U/EN U15 or higher) or H14 grade HEPA filters are required. Maintain a positive pressure difference of ≥10-15 Pa with the adjacent Grade B zone.
Grade B: Provides a high-cleanliness background environment for Grade A zones, preventing external contamination intrusion. H14 grade HEPA filters (efficiency ≥99.99% @ 0.3μm) are required as air supply terminals. Maintain apositive pressure difference of ≥10-15 Pa with the adjacent Grade C zone.
Grade C: H13 grade HEPA filters are used. In some high-standard projects, H14 grade filters can also be used to extend their lifespan. Maintain a positive pressure difference of ≥10 Pa with the adjacent Grade D zone.
Grade D: H13 grade HEPA filters or high-efficiency E10-E12 grade filters are used as terminals. Maintain a positive pressure difference of ≥5-10 Pa with the corridor outside the clean area.
III. Trenntech’s Optimization and Upgrade Practices
When designing a filling line solution for a biopharmaceutical client in Ludwigshafen, Trenntech faced the challenge of not only meeting static cleanroom requirements but also ensuring flawless operation during dynamic production. Trenntech‘s solution included:
1. Differentiated Precision Configuration: U16-grade (99.9995% efficiency) ULPA filters were configured for the Class A laminar flow hoods, with individual EN 1822 scan reports provided for each filter; the Class B background area used rigorously leak-tested H14-grade HEPA filters. Long-life H13-grade filters were selected for the Class C/D areas, optimizing overall cost.
2. Intelligent Differential Pressure and Airflow Management: By integrating differential pressure sensors and a variable frequency fan control system, the differential pressure between different cleanroom zones was dynamically adjusted to ensure that the airflow direction remained positive, flowing outward from the Class A zone, even under disturbances such as door opening and equipment startup.
3. Lifecycle Services: Providing a complete supply and replacement plan for filters from pre-filters, medium-efficiency filters to high-efficiency filters, and utilizing differential pressure monitoring data for predictive maintenance to avoid unplanned downtime and minimize the total cost of ownership of the filtration system.
With the rapid development of personalized medicine and biologics, the requirements for production environments will inevitably become increasingly stringent. In the future, Trenntech plans to build a full-chain, engineered filtration solution supply system covering standard product manufacturing, system design, intelligent monitoring, and data traceability, striving to become the most trusted partner in the pharmaceutical industry.