DEPYROGENATION PROCESS VALIDATION

Dry Heat Sterilization (or Depyrogenation) is a process aimed at the reduction in the level of pyrogens with the use of hot air in temperature ranges from 160°C up to 400°C. The temperature used depends on the duration of the process. There are two types of heat convection that can be used; gravity or mechanical. The former uses the natural interaction between air of different temperatures, and the later produces a specific flow of air with the help of a blower.

PROCESS EQUIPMENT

Depyrogenation processes can vary greatly depending on the technique used, the kind of the load and the product that is being sterilized. No matter what the specifics of your application are, Ellab has a flexible solution to cover your individual needs.

Ellab manufactures custom made mineral insulated semi-flexible metal sensors. Ellab high temperature sensors withstand exposure to temperatures up to 400°C and can be ordered in the length that your application requires. Their small diameter and ductile characteristic makes them perfect for measurements inside empty vials and their exact positioning in the cold spot. If there are space constraints inside the vessel, double sensors can be manufactured.

For the different process lengths, Ellab provides different thermal barriers. When monitoring depyrogenation processes, all wireless dataloggers need to be protected from the extreme temperatures. Ellab’s thermal barriers offer different levels of protection, depending on the length and temperature of your process, so you can optimize space and resources.

Our flat-pack is specially designed to provide high protection in tunnels with little headspace, making the set-up for your study simpler.

For real-time data collection during depyrogenation processes, the user is no longer required to use cables. Ellab’s SKY system allows for wireless radio transition of dat directly to the PC, for documentation and process control.

Depyrogenation is mainly used in the sterilization of vials for aseptic filling. The process is also useful to sterilize assembled and packed materials, since heat conduction does not require the contact of the product with steam or water. However, not all products can withstand the high temperatures required for this kind of process (eg. metal goods, heat sensitive solutions, etc).

There are two main techniques of depyrogenation; batch and dynamic. Batch form is usually done in static ovens where the product is placed in metal crates and exposed to high temperatures. Dynamic techniques involve the use of a depyrogenation tunnel, where goods are transported over a continuous band through the different heating zones of the tunnel.

CHALLENGES
Thermal processes above 250°C can easily damage the electronics and sensors of monitoring equipment resulting in the loss of valuable process data. Only high quality materials will provide a monitoring solution that is always reliable. When sterilizing empty glass vials by depyrogenation, the set-up of the monitoring equipment can be very fragile. Empty vials are easily tipped over and broken by movements of thermocouples during the process.

In dry heat sterilization processes, air is the heat transmitter, which poses specific concerns for correct sensor positioning if a worst-case scenario approach is to be taken. The use of semi-flex metal sensors minimizes inaccuracies in sensor positioning by keeping the desired shape during the complete process.

Depyrogentation tunnels offer limited headspace to optimize the sterilization process, making it difficult to introduce monitoring equipment. By using thermal barriers of different sizes, it is possible to find the best fit for the application. When the sterilization of small ampoules is being performed in a tunnel, the flat-pack offers a compact solution that is easily introduced with the load.

GUIDELINES

The PDA Technical Report No. 3 offers useful guidelines for the qualification of Dry Heat Sterilization processes.

The usual number and positioning of measuring points varies depending on the technique used. In a dynamic technique, temperature sensors are placed in three horizontal lines through all the load; one line at the beginning, one in the middle and the last one at the end of the batch. The number of sensors per line depends on the width of the tunnel, but five sensors are commonly used as a rule of thumb. In a static technique, temperature sensors are placed in different levels of each crate and the number of points can be as high as one five per crate.

METHOD

When creating the thermal profile for a dry heat sterilization process, the main tests to be performed are heat penetration and heat distribution. The former is concerned with the heat generation inside the vessel and it’s homogeneity and the later is focused on the heat transmitting from the vessel to the product and its effectiveness. This is normally measured in terms of lethality. The worst-case scenario is a recommended perspective as an acceptance criterion.

Data collection
Independent on the technique used for depyrogenation, static or dynamic, it is important to record simultaneous temperature data from a relevant number of points. In the case of a batch set-up it is recommended to use at least three points, but in the case of large vessels a larger number is recommended. For sterilization tunnels, a three-line set up is the most common way to place the sensors; one at the beginning of the batch, on in the middle and one at the end of the batch. The number of sensors per line is dependent on the width of the transport band. Creating and documenting sensor positioning is an important part of the documentation for the process control. Using the Unit tool inside the ValSuite™ software makes it possible to have a documented map of sensor placement that will facilitate repeatable and comparable studies.

Once the position of the sensors in the vessel has been documented, it is necessary to observe sensor placement inside the product. With the help of semi-flex metal sensors is possible to accurately locate the sensing element in the cold spot. It is important to take into account the kind of heat convection used in the vessel and the shape of the product for the correct assessment of the cold spot. ValSuite™ software facilitates the documentation of sensor placement in the cold spot by allowing users to include descriptive pictures per every channel used.

Data analysis
When all data is collected, the user must observe the homogeneity, stability and heat generation of the vessel, in order to create a good assessment of the heat distribution during all the phases of the process. Valsuite™ provides tools to analyze the performance of the vessel in all phases of the process. The use of time-markers helps to generate graphical and analytical reference points in the data collected. Statistics such as min. max, delta and Lethality Fh are also available in the software. Valsuite™ software integrates all calculations into self-generated reports without the need to export data into other software. Reports can also include the placement of the loggers inside the vessel and descriptive pictures of sensor positioning. Generating ValSuite™ reports provides the highest data security for the results, since the software is compliant with FDA 21 CFR Part 11.



Leave a Reply

You must be logged in to post a comment.