Page 220 - Assurance of Sterility for Sensitive Combination Products and Materials

Risk to the patient—Quantifying assurance of sterility 199

expectation of a survivor of a sterilization process is extremely low, there is
also the expectation that any survivor should also be one that is resistant to
the particular sterilization process. In that case, it should be relatively easy to
research the general ability of an organism that might survive the steriliza-
tion process to survive the storage environment (temperature and humidity)
as well as the time of storage.
On a product that does not support microbial growth, it is well un-
derstood that bioburden dies off with the passage of time [5]. Additionally,
small numbers of organisms on a device may be of little consequence to
the patient; however, the ability of the organisms to multiply is key to this
analysis. Bacterial and fungal growth requires consumables (nutrients) and
the right environment, that is, temperature and pH. Fortunately, nutrients
are generally unavailable on most sterile devices. Microorganisms have an
absolute requirement for water and water availability has a profound effect
on survival and growth [5]. The presence of water or moisture may be
present in some packaging or devices; however, this is not the norm. Some
organisms can grow in the absence of air (anaerobic), however, most require
oxygen (aerobic). Thus devices packaged in an inert gas limit microbial
growth. There is an optimum pH over which microorganisms can grow.
Bacteria grow best around pH 7 but many molds can tolerate more acidic
conditions, pH 5–6. Some microorganisms are surprisingly tolerant of hos-
tile pH environments [5]. The typical environment for a sterile device is pH
neutral and does not deter growth. As with pH, there is an optimum tem-
perature range for microbial growth. Low-temperatures slow growth rates
while higher temperatures increase growth rates. Storage environments are
varied and may include hot or cold temperatures and dry or moist condi-
tions for periods of time during shipping. Typical hospital device storage is
at room temperature which does not deter growth.
Knowing the length of time and storage/transport conditions that would
occur between sterilization and patient use, one can estimate the probability
of survival. Another factor is the possibility that the organism was damaged
from the sterilization process. All of this information can be used to estimate
the probability of an organism that might have survived sterilization to still
be viable at the time of use of the product.
A conservative example of a value for P2 would be a 1 in 2 chance that
an organism would still be viable at the time of use, possibly based on the
bioburden having spores, the product being one that may support growth,
the lead time between sterilization and use being shorter, and there being
controlled shipping/storage conditions. A more realistic example of a value