Number of microbes deposited on product = C × S × Pd × Pa × T
in which C is the concentration of microbes in the source (people), S is the quantity of air or material dispersed from a source over time (usually cfu/m3/s), Pd is the proportion of organisms effectively transferred, Pa is the proportion of organisms that arrive into the product area, and T is the time during which microbes could be transferred.
Whyte also has proposed a slightly simpler deposition model for risk evaluation in which the risk from microbial contamination
is defined as:
Risk = A × B × C × D
in which A is the microbial contamination on or arising from a source (e.g., glove or air), B is the ease of dispersion or transfer, C is the proximity of the source to the critical area (one can assume the contamination decreases as the inverse of the square
of the distance), and D is the effectiveness of the control method (e.g., isolator, restricted-access barrier systems [RABS], automation, sealed container, intervention frequency).
Whyte chose five levels of risk for each of the terms in the equation: 0 indicates no risk, 0.5 indicates very low risk, 1
indicates low risk, 1.5 indicates medium risk, and 2 indicates high risk. In the case of factor D (effectiveness of control), he suggests 0 for "full barrier control." This means that, should a truly full barrier exist,
the overall risk effectively would be zero. Products such as sealed vials that mimic the capabilities of a closed isolator
system logically would fall into the "full barrier control" category (9, 10).
The authors' main criticism of this risk model is that it may underestimate process risk because it implies that an exclusionary
process such as aseptic processing could produce a level of contamination control effectively equivalent to terminal sterilization.
Certainly aseptic processing, in its present state, cannot be considered equivalent to terminal sterilization. Although it
may be possible in the future for extremely advanced aseptic processing to achieve levels of actual product safety equivalent
to those attained using terminal sterilization processes, there are no aseptic systems currently in operation that can attain
process capability comparable with that of a terminal sterilization process. Furthermore, the destructive control afforded
by terminal processes enables scientists and engineers to assess risk far more reliably than is possible in aseptic processing.
The deposition models for contamination risk analysis have their advantages and disadvantages. They take into account the
following technical conditions that have been included in informal risk assessment for years:
- the size of container opening;
- the exposure time for the container;
- the estimated microbial content of the surrounding air.
The authors believe that a major disadvantage of these models is their inherent assumption that the deposition of microorganisms
from the air represents the only vector for contamination. Having observed numerous aseptic processes over the years, the
authors find that approach inadequate. In many aseptic processes, operators must approach sterile materials with tools and
protective measures. Focusing on personnel seems more appropriate. Although deposition may be the mechanism of dispersion,
one must not be so focused on the containers that one ignores the potential presence of microorganisms in other stages of
the aseptic process. The authors have developed an approach that is much broader and is not limited to the effect on the container
In addition, the authors believe that assumptions regarding the microbial content of air are potentially misleading. It is
tempting to consider that the worst-case content of airborne microbial contamination is that given in the common international
recommendations (i.e., <1 cfu/m3).