Real Time Product Temperature Monitoring
The product temperature is the most important critical quality attribute in a freeze drying process. For example, product temperature above the critical formulation temperature during primary drying commonly results in severe damage to the product. The wireless and battery-free Tempris sensors can be applied on all scales of freeze dryers and thereby provide the most comparable and consistent data for this parameter in real time throughout development, transfer and production of a lyophilized product, even in combination with automatic loading systems.
In a freeze drying process, product temperature cannot be controlled directly, but is determined by a combination of process and product parameters. The shelf temperature and chamber pressure are controlled directly based on the user-defined recipe, and constitute the main variables for achieving a suitable product temperature over time profile.
Another important factor, with high impact on product temperature is the product resistance over the dried layer, Rp; which again depends on the solute concentration, cake thickness and freezing conditions. High product resistance against the flow of water vapor through the dried layer leads to elevated product temperature.
Further parameters influence the product temperature as well, such as the geometry of the container system, the extent of radiative heat transfer to the vials, and the physicochemical state of the product. Due to this multitude of factors, it is very difficult to keep all product units within the batch at a target product temperature throughout the process. This challenge can be overcome by application of Tempris, a process analytical technology capable of measuring the product temperature in real time.
Tempris sensors were specifically designed for monitoring and optimization of freeze-drying processes, and have proven their reliability in many industrial and academic applications. Tempris has a variety of advantages over other temperature sensors applied in freeze drying:
Tempris is a modular system, can be installed either as a retrofit or a stand-alone unit for any type of freeze dryer irrespective of the design from laboratory scale up to commercial production. This provides unparalleled comparability of product temperature data obtained from early development up to routine manufacture. This consistency in information on the most important critical quality attributes can also be valuable for preparation of regulatory submissions
Tempris sensors are feasible with Robotic, Automatic loading and unloading systems. Monitor Tp on the desired shelf positions inside the lyo chamber. Easy to handle inside Restricted Access Barrier System (RABS) and/or Isolator. Suitable for commercial production in a cGMP environment
Tempris sensors do not contain a battery, but function passively which prevents heat transfer to the product as is the case for other temperature sensors. The sensors do not have a limit for the operation duration, and do not require recharging. The lack of batteries also promotes their safety and usability in commercial production equipment compared to other systems
Due to the wireless construction, the sensors can be pre-sterilized, placed into vials and introduced into the freeze dryer through automatic loading systems, enabling flexible placement at target positions for versatile applications, e.g. monitoring of worst-case positions or comparison of edge and center positions
All materials used in the Tempris system are suitable for cGMP environment, can be steam sterilized and can be applied during aseptic manufacturing processes
Tempris is compliant with 21CFR Part 11 (FDA) and GAMP 5 (EMA)
Each sensor is calibrated individually prior to delivery and supplied with a certificate
Tempris sensors measure the product temperature at the bottom of the vial, Tb, with an accuracy of ± 0.7°C over a temperature range from -60°C to +60°C
Tempris sensor design allows exact determination of the temperature at the measurement tip. Since the position of the tip can be reliably positioned exactly at the center-bottom of the vial using a specific positioning device called centering crosspiece (CCP), the loss of contact to the ice is a valuable indicator of the drying endpoint. Different scientific investigations also reported that the Tempris sensors maintained contact with the ice during primary drying longer than thin wire thermocouples. Temperature data during primary drying also corresponds with Tb calculated from manometric temperature measurements (MTM)
The Tempris Data Monitoring software provides direct and clear visualization of the recorded temperature data during the process. The system also stores the positions of the individual sensors and offers various evaluation functions and user-specific configurations:
- Data Logging and Data Visualization
- cGMP/GAMP5 Compliant
- FDA 21 CFR Part 11 Complint
- User Administration
- Audit Trial
- Back Up
- Log File Reports
- CSV Export
- Automation Interfaces to PLC / SCADA
- Sensor Function Check
The Tempris system can be integrated into PLC or SPS based freeze dryer control systems, so that the product temperature data becomes part of the cGMP routine environment. The temperature data can also be exported into Excel-compatible formats, allowing further detailed analysis of the results