Calculating And Understanding Particulate Contamination Risk - Pharmaceutical Technology

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Calculating And Understanding Particulate Contamination Risk
The author presents a method to calculate the relationship between supply air volume flow and airborne particle concentrations. These methods and approaches facilitate the overall understanding of airborne contaminants and provide valuable information when designing facilities and processes for sterile manufacturing.

Pharmaceutical Technology Europe
Volume 23, Issue 3

Table 1: Calculated contamination rate in containers — settling velocity from gravity.
If only the convective effect is considered, the equation can be used to calculate the number of deposited particles in UDF, which enables the contamination risks for different types of processes to be calculated. Whyte gives examples of how to calculate contamination rates for different container sizes and exposure times, regarding gravity settling time (Table 1). In most sterile processes, 1.350 bacteria/m3 is considered to be a high value. For example, a Grade D cleanroom environment according to EU GMP is defined as having a limit less than 200 CFU (viable particles)/m3 . Whyte reports an average value of 0.2 bacteria/m3 in a wellworking UDF unit (corresponding to Grade A clean room designation per EU GMP). This demonstrates a significant change in increased product safety in the calculation.

Table 2: Calculated Contamination Rate in Containers — settling velocity from UDF.
A comparison of contamination rates can be conducted if the settling velocity from gravity in the calculation is replaced by convective settling velocity. Results in Table 2 present calculations for the same containers as Table 1, except for their placement under a UDF unit (Grade A), with a UDF velocity of 40 cm/s. Calculations are based on the assumption that gravity force is negligible. Grade A, according to the EU GMP recommended limit of less than 1 CFU/m3 is used in the calculation, but so too is an average value of 0.2 CFU/m3 because this more accurately represents a true UDF environment.

In Table 2, where the calculations are adapted to UDF, there is a higher potential risk of contamination of the containers. With a wellworking UDF unit and operation routines; however, the amount of airborne viable particles (CFU/m3 ) is most likely lower than 0.2 CFU/m3 . When applying Equation 1 in a volume with completely mixing air or with no air movements, the Stokes law (Equation 2) must be used to calculate settling velocity for particles. In a UDF, the settling velocity is equal to the air velocity.

As demonstrated by the calculations, contamination rates are dependent on different factors. It is not only the amount of airborne viable particles that must be considered; so too must the exposure time and the exposed area to those viable particles. Sundström, Ljungqvist and Reinmüller have used this model to calculate particle concentrations in small-volume parenterals produced by blow-fill-seal technology.6 They have also performed experimental studies with analyses of the amount of particles that disperse into the ampoule from the surroundings as a comparison to the theoretical method.

This knowledge can be used for various purposes. One example is during investigations of deviations in the amount of airborne viable particles (CFU/m3 ) within a cleanroom. The model can be used to calculate the risk of contaminating a container or surface, although an investigation as described has to be more complex, and other practical and experimental methods will need to be considered.


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