Depyrogenation Oven & Heat Tunnel Validation
Depyrogenation Oven & Heat Tunnel Qualification – Performed by Ellab
Ellab performs qualification and/or validation of depyrogenation ovens & Tunnels throughout North America for our clients.
Qualification and/or validation performed by Ellab will typically include:
- Ellab generation of qualification protocol or utilization of client’s protocol
- Execution of qualification protocol
- Installation Qualification (IQ)
- Operational Qualification (OQ)
- Heat Distribution studies: The unit will be mapped empty with temperature sensors placed throughout the oven to measure uniformity, stability, and repeatability.
- Performance Qualification (PQ)
- Heat penetration studies: Load temperature mapping, which may include endotoxin challenge studies with inoculated samples.
- Utilization of Ellab’s validation equipment
- Thermocouple based
- E-Val Pro
- Ellab validation thermocouples
- Kapton coated Ultra-Premium Type T thermocouples
- E-Val Pro
- Data Logger Based
- Tracksense® Pro
- Semi Flex sensors leveraged with thermal barriers may be utilized
- Tracksense® Pro
- Thermocouple based
- Report completion and Summary Report
Depyrogenation Oven Overview
A depyrogenation oven and tunnels use dry heat for the removal of pyrogens from various heat-resistant pharmaceutical products and process equipment, most commonly glass vials used for aseptic filling. Pyrogens are thermally stable and are not removed though common sterilization processes, such as autoclaving, but extended exposure to elevated temperatures will remove them. For example, a thirty-minute exposure at 250°C will cause a 3 log reduction in the pyrogen count. Temperatures typically range from 160°C to 400°C, but can vary depending on the length of exposure and thermal stability of the product.
Batch processes can be performed in an oven, where product is placed in the chamber for a cycle and removed. Ovens should have an air pressure differential controlled to prevent flow from the dirty to clean sides of the unit. Additionally, door interlocks should be used for both safety and to prevent flow between clean and dirty process areas.
Continuous processes can be performed in a depyrogenation tunnel, where product is conveyed through different temperature zones while being transported from one area to another. There are typically three zones: preheat zone, heat zone, and cooling zone. Conveyor speed is a critical parameter, as this is the means of control for warm-up, exposure and cool down times. Multiple temperature profiles and conveyor speeds may be qualified and used for different load items. As with the ovens, air differentials should be used to create sterile boundaries and prevent cross contamination between sections of the oven and process areas.
The qualification of a depyrogenation oven or tunnel requires validation sensors that can withstand exposure to extremely high temperatures. Ellab offers several solutions that are recommended for this application:
- Thermal Barriers, which are available in five sizes and offer protection for the sensors and loggers from temperatures ranging from 200°C to 400°C.
- TrackSense™ Pro High Temperature Sensors, offering accuracy of ±0.5°C over the range of 0°C to 400°C.
- E-Val™ Pro with high-temperature STC-KT thermocouples, with an accuracy of <0.5°C over the range of 0°C to 260°C, with a short-term exposure limit up to 350°C.
For applications with specific size restraints, Ellab also offers custom mineral-insulated semi-flexible metal sensors that can be cut in various lengths. The customization allows for the sensors to be used in any size vial or packaging that may otherwise pose spacing challenges.
The qualification of a temperature profile requires both distribution and penetration temperature mapping, allowing for the verification of both an even temperature distribution throughout the chamber and adequate heat penetration for required lethality collection. Additionally, it is imperative that sensors are located in the hardest-to-heat location within each load item and, if applicable, the hardest-to-heat load item is placed in the hardest-to-heat location within the chamber. The hardest-to-heat locations are determined by the location with the lowest lethality value (FH) during the empty chamber mapping, and the item with the lowest lethality during item temperature mapping.
As the depyrogenation process is driven by heat transfer between dry air and the product, it is crucial that sensor placement does not impede the flow of air around and through the product to be sterilized. Semi-flexible metal temperature sensors allow for some freedom in logger placement while maintaining the placement of the sensor, to ensure that the hardest-to-heat location temperature is captured in the study data.
Ellab offers an extensive catalog of validation equipment that is designed for the qualification of dry-heat sterilizers, and our validation staff are well experienced in writing and executing the necessary validation documentation for your depyrogenation oven or tunnel qualification.
Standards and Guidelines
- PDA Technical Report no. 3 – Offers guidance and industry practices for pharmaceutical manufactures in their approach to the validation of dry-heat sterilization processes. Also provides various aspects of validation using biological and endotoxin indicators.
- ISO 20857:2010 – Specifies requirements for developing and validating dry-heat sterilization and depyrogenation processes.