Page 39 - Assurance of Sterility for Sensitive Combination Products and Materials

Terminal sterilization 27

in the 1990s. Both moist and dry heat rely on the same fundamental mech-
anism to inactivate microorganisms. The thermal energy results in the de-
naturation of proteins and enzymes. This loss of functionality of enzymes
causes the death of the organism. The difference in the efficiency between
dry and moist heat arises from the difference in efficiency with which the
thermal energy is transmitted to the organism. In dry heat, the energy is
transmitted by the conduction of heat through air. This is relatively ineffi-
cient. Moist heat sterilizations rely on the high latent heat of vaporization
to efficiently transfer heat from the steam to the microbes to affect the kill.
As the saturated steam interacts with the surface, it condenses, transferring
the heat to the surface. The change in phase from gas to liquid also results
in a reduction in volume which in turn draws more gas to the surface. This
process continues until the surface equilibrates in temperature with the
steam. As this energy interacts with the organism, it rapidly raises the tem-
perature of the cell. This denatures the proteins, enzymes, and DNA. The
denaturation of the enzymes results in the loss of function and death of the
organism. Key factors which govern both dry and moist heat sterilization
are as follows:

Factor Dry Moist
Barriers Thermal Thermal and tortuosity
path
Temperature Of oven Of Steam
Pressure No Yes
Time Yes Yes

3.2 Sterile validation of current methods

The risk of non-sterile product reaching the patient is extremely low, but
the criticality is high because many of the device combination products are
parenteral or implantable. Even if the probability of the event happening is
very low, the impact can be catastrophic. The paradox for sterility testing
is that the low incident rate and the destructive nature of the testing make
the verification strategies impractical. The validation of a terminal steril-
ization process requires qualification of the product, the equipment, and
the process. The definition of packaging constraints, microbial quantity, and
quality of the product are all needed to meet the rigor of validation. In con-
trast to aseptic processing, the validation of the terminal sterilization process