Processing heat penetration

The sterilization test functions required to qualify or validate the sterilizer will include process heat distribution, process heat penetration, and process microbial and depyrogenation validation, as applicable. 

Heat penetration is the most critical component of the entire validation process. Heat penetration studies will be performed per plant SOP. Using four shelves of the trolley, distribute the load per following sequence ... 

In the case of heat sterilization processes, the supporting data required include heat distribution and heat penetration studies (usually at least three runs at the minimum process parameters), with calculation of... 

Load cool points are dependent on load conhgurations and the types of items that comprise the load (liquid-hlled containers, process equipment, etc.). Prior to conducting heat penetration studies, maximum and minimum load conhgurations must be established. The penetration thermocouples are positioned within liquid-hlled containers at the cool point previously determined by container mapping studies. The probed containers should be distributed uniformly throughout the load. When the load consists of multiple layers or pallets, a sufficient number of thermo-couple-probed containers should be employed to provide an equal representation among layers. 

A heat penetration study dehning load cool points is not limited to load conhgurations composed of liquid-hlled vials. The same principles can be applied to process equipment loads (hlters, hoses, etc.) subject to steam sterilization. Penetration thermocouples are positioned at points within the process equipment suspected to be the most difficult for steam heat penetration. Temperature data are obtained from representative maximum and minimum loads in order to establish temperature prohles... 

Heat penetration studies are also employed to determine points within a load configuration that achieve higher temperatures and consequently greater Fq values. The temperature data obtained may be significant when heatable products are involved in the sterilization process and the potential for product degradation exists. The cool points established for a specified load and configuration will eventually be utilized to control the exposure time in subsequent routine production runs. The temperature sensors that control sterilization-cycle-exposure time at process temperature may be positioned within the load at the previously detected cool point. Consequently the entire load is exposed to sufficient heat lethality and achieves the desired Fq value. 

Biological castles are employed during heat penetration situations in order to demonstrate the degree of process lethality provided by the sterilization cycle. Calibrated biological indicators utilized for this purpose function as bioburden models providing data that can be utilized to calculate Fq or substantiate and supplement physical temperature measurements obtained from thermocouples. 

To ensure sterility during the aseptic processing, it was decided to revalidate the A-ml and B-ml vials sterilization and depyrogenation cycle by one heat penetration study and endotoxin challenge test once in a year. 

Heat penetration is the most critical component of the entire validation process. 

The sterile solutions are filled in different sizes of ampoules/vials under aseptic conditions. For this purpose, all operations and conditions should be validated according to the approved protocols to ensure the sterility during the aseptic processing to validate the sterilization cycle for A-ml vial filling machine parts and accessories by three heat penetration studies and a microbial challenge test using B. stererotbermophilus strip. 

If one knows the D value, the BI concentration or population A and the desired probability level of nonsterility B, the minimum F0 value that must be achieved by the sterilization cycle for the particular load can be calculated. For example, if A = 106 and II = 1 (f6 and laboratory studies determine the D value for B. stearothermophilus in the product to be sterilized to be 0.4 min (F0 = 0.4(12) = 4.8 min), a minimum F0 value of 4.8 min should be achieved at the worst case location during heat-penetration studies. The USP requires a steam sterilization process to deliver a lethality input of 12D for a typical overkill approach. 

This is the most critical component of the entire validation process. The success of a validated cycle depends on determining the F0 value of the cold spot inside the commodity located at the cool spot previously determined from heat-distribution studies. The container cold spot for containers >100 ml is determined using container-mapping studies. Thermocouple probes are inserted within a container and repeat cycles are run to establish the point inside the container that is coldest most of the time. It is this exact point that is monitored during heat-penetration studies. 

These processes have an advantage in that the heat penetrates deeply into the joint and into the epoxy material itself. With conventional thermal energy processes, the heat must be conducted into the mass of the epoxy adhesive from outside the joint. This is hindered by the presence of the substrates, the substrate geometry, and the relatively low thermal conductivity of the epoxy itself. 

The viscous liquid is passed at low velocity through the central tube. Portions of this liquid adjacent to the heat-transfer surface are essentially stagnant, except when disturbed by the passage of the scraper blade. Heat is transferred to the viscous liquid by unsteady-state conduction. If the time between disturbances is short, as it usually is, the heat penetrates only a small distance into the stagnant liquid, and the process is exactly analogous to unsteady-state heat transfer to a semi-infinite solid. 

The physical parameters of the process are monitored in normal production runs to obtain additional information on the process and its reliability. Extra temperature-sensitive devices installed in an autoclave or dry-heat sterilizer (in addition to probes used routinely) will permit an in-depth study of the heat distribution for several loads. Heat-penetration measurements are recommended for injectable products of higher viscosity or with volumes larger than 5 ml. A tableting press equipped with pressure-sensitive cells will be helpful in collecting statistical data on the uniformity of die-fill and therefore on mass uniformity. 

All penetrations are welded to the fixed vessel lid. Although not illustrated in Figure 12.5, all pipework connected to the process vessels is designed to present minimum dead legs, with aspect ratio of ca, 1 1, minimum 1 inch length, to ensure free draining and heat penetration. 

An example of a process step with a relatively high risk is the incorrect loading of the sterUiser. Here the severity is 5 (insufficient heat penetration in certain units by incorrect loading), the probability of occurrence is 2 (a load instruction is in place) and the risk of non-detection 3 ((Mily one person is loading and unloading and cmitrols the load), so, RPN = 2x3 X 5 = 30. This process step needs more attentirm than the other example. 

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