NEWSLETTER
ISSUE
Apr to Jun, 2021 Volume 14
BRAIN WAVE
Importance of Sterilization and Various cycles in Pharmaceutical manufacturing – Part 4
In continuation with the previous discussion on the importance of sterilization cycles, let us understand the significance of the following cycles in the current issue.
- F0 Cycle
- Bowie-Dick Test cycle
- Vacuum Leak Test cycle
F0 Cycle
F0 is also known as Lethality Factor. The F0 value for a given temperature during sterilization indicates an equivalent sterilization time (in minutes) that would have taken if the load were at the sterilization temperature of 1210C. Sterilizing a product using the F0 helps to avoid prolonged exposure of heat-sensitive material and large volume liquids to a higher temperature. Thus, the F0 cycle facilitates effective sterilization without material deterioration and aids, increasing the overall efficiency of the process.
A standard sterilization cycle comprises of heating phase, sterilization phase and exhaust phase. The heating phase generally requires 30 to 90 minutes, followed by a sterilization phase of 20 to 40 minutes. For heat-sensitive material or large volume liquid, such prolonged exposure to temperature can be critical and undesirable. Under such critical circumstances, the F0 cycle enables sterilization of the load with a shorter exposure time. Additionally, the F0 value estimation theoretically confirms the effective completion of sterilization.
Fundamentally, the F0 cycle considers the sterilization (microbial kill), which is taking place while the load is being heated, i.e., lethality achieved during the heating phase. The F0 value is calculated intermittently during the cycle and summed up to estimate the total F0 value. Upon attaining the desired F0 value, sterilization is said to be achieved irrespective of the time and temperature attained by the load.
For example, if the load was at 1100C for 25 minutes, it achieves sterilization equivalent of 2 minutes at 1210C
Bowie-Dick Cycle
Bowie-Dick cycle is employed in various applications such as sterilization of pharmaceutical goods, medical devices, and waste from bio-containment laboratories. It is primarily used for the operational testing of a pre-vacuum sterilizer. This test cycle reveals the capability of the sterilizer to remove adequate air from the chamber. The removal of air from the chamber is critical for successfully sterilizing porous loads in the pre-vacuum sterilizer. The presence of air within the chamber acts as a barrier for steam penetration in the porous load, thereby preventing effective sterilization.
Additionally, the Bowie-Dick cycle helps verify the quality of steam used for sterilization of critical load. And it also evaluates the temperature & pressure of saturated steam during the sterilization phase.
The Bowie-Dick cycle is performed using a small disposable pack. This pack consist of thermochromatic paper sandwiched between the porous substrates & reticulated foam. The pack is placed on the bottom rack, over the chamber drain, in an empty sterilizer. Any residual air in the chamber will pass through the test pack while drawing a vacuum through the chamber drain. The cycle starts with 3 to 4 pre-vacuum pulses, followed by heating to the set temperature.
After completion of a cycle, the test pack is opened to check the results. The thermochromatic paper changes the colour if the steam penetrates through the porous material. If the pack shows uniform colour change, the result is “pass”, indicating successful air removal and full steam penetration. And if there is no or partial colour change, the result is “fail”.
The Bowie-Dick cycle is used for sterilizer qualification and in routine monitoring. For qualification, generally, three consecutive cycles should pass the test, whereas, for routine monitoring, only one cycle should pass the test. The routine test can be performed daily or as per the SOP. If the test fails, the sterilizer and the utilities should be checked.
Typically, the pre-vacuum sterilizer is employed to sterilize porous loads such as garments, wrapped goods or packs. For successful sterilization of porous loads, air removal from the chamber is critical. The presence of air within the chamber acts as a barrier for steam penetration in the porous load, preventing proper sterilization.
Vacuum Leak Test
A vacuum leak test is used to check the airtightness of the sterilization chamber & the piping system. Airtight integrity of the system is essential as any leakage of air into the system will hinder the effective sterilization of the load.
During the vacuum leak test, the system is exposed to a high vacuum, and then the loss in the level of vacuum is measured per unit time (i.e., leak rate) to define the system as Pass or Fail. A typical vacuum leak test cycle consists of a vacuum pulse, followed by stabilization timeand dwell time. During the vacuum pulse, a pressure of 70millibar abs. or below is attained in the chamber. Post vacuum pulse, a stabilization time of 5 to 10 minutes is given to allow evaporation of condensate from the chamber. The stabilization time is then followed by 10 minutes of dwell time to measure the leak rate. Upon completion of the cycle, the leak rate is estimated and compared with the acceptance criteria. The industry standard for allowable average leak rate is 1.33 millibar/minute. If the leak rate is within the standard limit, the system Passes the test, and if it is above the standard limit, the system fails the test.
The vacuum leak test should be performed only when the chamber is empty, dry and at room temperature. The test should be performed regularly depending on the SOP and level of risk, as the vacuum leak test helps avoid failed sterilization.
