As a practical example, the model can be used to calculate the contamination rate if the exposure time for ampoules in a blowfillseal
filling machine is increased. Many types of blowfillseal filling machines generate a high amount of particles during plastic
extrusion. Often, these particles are removed through local exhaust devices inside the machine region. To improve the local
exhaust devices and thereby remove more airborne particles, the cycle time was increased, allowing the mould to stay at the
extrusion position for a longer time. In this case, the concentration of airborne particles in the filling machine was reduced.
However, the increased cycle time and exposure time must also be taken into account when evaluating the overall risk situation.
The calculated contamination rate was increased 20% due to increased exposure time (20% longer). The concentration of airborne
particles was decreased by 25%. In the end, considering both the increased exposure time and the reduced concentration of
airborne particles, the contamination risk decreased by 5%.
As another example, comparisons can be made between different filling techniques. If vials in filling process A have the same
exposed area, airborne concentration and settling velocity as ampoules in process B, but twice the exposure time, the calculated
contamination rate is doubled for process A. The guidelines1,2 do not make any exceptions between these two techniques, but in theory, the airborne concentration at process B could be
twice as high as for process A and still have equal contamination risk.
The calculation models presented in this article can be helpful in calculating risk factors and increasing the understanding
of contamination caused by airborne particles. The method described shows that it is possible to calculate the risk factor
or the rate of contaminations to a certain area. The theoretical risk to contaminate, for example, a container or ampoule,
depends on the exposed neck area, airborne particle concentration and exposure time.
Mattias Haag is Validation Manager at Energo, Stockholm (Sweden).
Tel. +46 10 470 60 00
1. EU GMP European Commission, The Rules Governing Medicinal Products in the European Union, Vol. 4, EU Guidelines to Good Manufacturing
Practice, Annex 1, Manufacture of Sterile Medicinal Products, 1997 (revised 2008).
2. Food and Drug Administration. Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – Current Good
Manufacturing Practice. Rockville, MD, 2004.
3. B. Ljungqvist and B. Reinmüller, Clean Room Design: Minimizing Contamination Through Proper Design (CRC Press LLC, Boca Raton, Florida, USA, 1997).
4. B. Ljungqvist, Some Observations on the Interaction Between Air Movements and the Dispersion of Pollution: Document D8:1979,
Swedish Council for Building Research, Stockholm, Sweden (1979).
5. W. Whyte, Journal of Parenteral Science & Technology, 40(5) 188-197 (1986).
6. S. Sundström, B. Ljungqvist and B. Reinmüller, European Journal of parenteral & Pharmaceutical Science, 15(3) 87–92 (2010).