Point of discussion:
Should I be concerned about normalizing data for grade A and B areas?
Background:
According to current guidelines for manufacturing in cleanrooms, the standard unit of measurement for quantifying active air sampling results is Colony-Forming Units per cubic meter (CFU/m³).
In grade A cleanroom environments, EU GMP Vol. 4 Annex 1 (2022 Revision) requires continuous active air monitoring for the entire duration of critical operations, including assembly/set-up phase. A similar approach should also be considered for Grade B environments:
“9.24 Continuous viable air monitoring in grade A (e.g. air sampling or settle plates) should be undertaken for the full duration of critical processing, including equipment (aseptic set-up) assembly and critical processing. A similar approach should be considered for grade B cleanrooms based on the risk of impact on the aseptic processing.” (Ref. EU GMP Annex 1, 2022)
Consequently, the volume of sampled air in these areas (closely related to duration and flow rate) could exceed one cubic meter during the monitoring period.
For air monitoring (both viable and total particle counts), when the duration of a production process exceeds the time needed to sample 1 m³ of air, it is not recommended to normalize the results to 1 m³. Specifically, for viable active air sampling, it is important to consider the three following factors:
- Contaminants are not uniformly distributed over time or in space.
- Colony Forming Units (CFUs) are distinct, non-fractionable units.
- In grade A environments (most critical from product point of view), the expected limit is “no growth”.
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This paper discusses:
- Details on the factors for viable active air sampling listed above
- A recommended approach for sampling microbial contamination in grade A and B areas
- Examples of calculations for routine continuous sampling with the recommended approach
- A Note on Alternatives to CFU/m³ in Grade B Environments
- Conclusions from a PMS Perspective
