This informal CPD article ‘The Role of Airflow and Cleanroom Design in Contamination Control', was provided by Pharmalliance Consulting, who offer specialist support to pharmaceutical companies to maintain and increase quality compliance levels.
Introduction
In sterile pharmaceutical manufacturing, cleanrooms play a critical role in keeping contamination under control. EU Annex 1 highlights the importance of airflow design, air classification and pressure differentials in maintaining aseptic conditions. Poor airflow can introduce contaminants, disrupt clean air patterns and put sterility at risk. A well-designed cleanroom, backed by ongoing environmental monitoring, is key to preventing these issues.
Air Classification and EU Annex 1 Compliance
Cleanrooms are classified based on how many airborne particles are allowed in each zone. EU Annex 1 follows ISO 14644-1 standards, dividing cleanrooms into four main grades:
- Grade A: The most critical areas, such as filling zones and open product exposure points. These require unidirectional airflow, HEPA filtration and strict microbial limits.
- Grade B: Background areas for Grade A zones, with controlled levels of both viable and non-viable particles.
- Grade C: Areas with moderate contamination control, typically used in early manufacturing stages.
- Grade D: The least controlled areas, which still require validated cleaning and air handling.
To maintain these classifications, manufacturers need to monitor airflow, validate filtration efficiency and ensure contamination levels stay within limits.
Airflow Patterns and Their Importance
Cleanroom airflow must be carefully designed to remove contaminants and prevent them from settling in critical areas. EU Annex 1 sets out different airflow requirements depending on the cleanroom grade.
- Unidirectional airflow is required in Grade A zones. HEPA-filtered air moves in a steady, controlled direction, sweeping particles away from sterile areas. Even small disturbances can cause contamination to circulate, so smoke studies are used to check airflow patterns.
- Turbulent airflow is used in Grades C and D. Air mixes and dilutes contaminants, but if the system isn’t designed properly, it can create stagnant areas where particles build up.
Cleanrooms also use pressure differentials to keep less clean air from moving into critical zones. EU Annex 1 recommends the following pressure differences between areas:
- Grade A to Grade B: >10-15 Pa.
- Grade B to Grade C: >10-15 Pa.
- Grade C to Grade D: >5 Pa.
Controlling Air Contamination Risks
Several factors help keep cleanroom air clean and contamination risks low.
- HEPA filters capture at least 99.97% of airborne particles 0.3 µm or larger. They are critical in Grade A and B areas and must be tested regularly to confirm they are working properly.
- Air change rates (ACH) help maintain clean conditions:
- Grade A/B areas: 20-40 air changes per hour.
- Turbulent airflow areas: 10-20 air changes per hour, depending on risk assessments.
- If air isn’t refreshed often enough, contamination can build up, leading to
regulatory issues.
Conclusion
Effective airflow design and proper cleanroom classification are key to controlling contamination in sterile pharmaceutical manufacturing. EU Annex 1 outlines strict requirements for air quality, filtration and pressure management to keep aseptic conditions intact. To meet these standards, manufacturers must focus on maintaining controlled airflow, using reliable filtration systems and actively managing contamination risks. This not only ensures compliance but also protects product quality and patient safety.
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References
The European Commission, 2022. EU Annex 1, Brussels, Belgium.
