VALIDATION OF STEAM STERILIZATION CYCLES General Considerations

The literature contains more information on steam sterilization validation than
any other process in the sterile product area. One reason was the publication of
the proposed CGMPs for LVPs in June 1976. Actually, the FDA had been
surveying the LVP industry long before the proposed CGMPs for LVP regulations
were published. One of the major areas of concern was sterility and the
heat sterilization processes for achieving sterility. Thus, at least three sections of
the proposed CGMPs for LVPs contain statements related to steam sterilization
validation. Although these regulations have not become officially and legally
valid, they are taken seriously by the parenteral industry. Table 4 summarizes
CGMP-LVP statements pertaining to steam sterilization validation.
The key expression used in steam sterilization validation is F0. Interestingly,
despite the familiarity of this term, it is still misunderstood or misused in
the parenteral industry. The main purpose of the F0 value is to express in a
single quantitative term the equivalent time at which a microbial population
having a Z value of 10°C has resided at a temperature of 121.1°C. The time
units here are not clock time units; rather, F0 time is a complete summary of
the time the indicator organism spent during the entire cycle at a temperature of
exactly 121.1°C plus a fraction of the times spent at temperatures below
121.1°C, in addition to a multiple of the times spent at temperatures greater than
121.1°C. F0 is a summation term, as exemplified in Figure 3 and Table 1. F0 is
a time value that is referenced to 121.1°C. It includes heat effects on microorganisms
during the heating and cooling phases of the cycle, taking into account
that heat effects below 121.1°C are not as powerful in destroying microbial
life as the effect found at 121.1°C.
F0 values may be calculated in several ways. The basic way is by manually
recording the temperature of the monitored product at specific time intervals,
substituting the recorded temperature for T in Eq. (7), solving the exponential
part of the equation for all temperatures recorded, and then multiplying by Δt.
This was done in Table 1. Alternatively, and more expediently, a computer
program can integrate the temperature and time data to obtain the F0 value.
This approach is now widely used because of the availability of programmable
multipoint recorders that record temperature and solve the F0 equation on an
accumulative basis.