Real-Time Product Temperature Monitoring in Freeze-Drying

During the freeze-drying process, product temperature is the most important parameter. Therefore, real-time temperature monitoring of the product temperature is essential for the quality of the finished product. 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 sensor is applicable on all scales of freeze dryers. It thereby provides the most comparable and consistent data for this parameter. In real time. Throughout the development, transfer, and production of a lyophilized product. Even in combination with automatic loading systems.

In a freeze-drying process (especially during primary drying), product temperature cannot be controlled directly. Thus, it 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. Indeed, they constitute the main variables for achieving a suitable product temperature over time profile.

Another essential factor with a high impact on product temperature in freeze-drying is the product resistance through 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 and slower drying.

Other 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 applying Tempris, a process analytical technology capable of real-time temperature monitoring of the product temperature.

Here is a temperature curve of a freeze-dryer out of the TLM Software for real-time temperature monitoring

Tempris Features for real-time temperature monitoring

We specifically designed Tempris temperature sensors for real-time temperature monitoring and optimization of freeze-drying processes. They have proven their reliability in many industrial and academic applications. Tempris sensors have a variety of advantages over other sensors measuring temperature in freeze drying:

Tempris is a modular system that can be installed either as a retrofit or a stand-alone unit for any freeze-dryer, irrespective of the design, from laboratory scale up to commercial production. This provides unparalleled comparability of product temperature data from early development to routine manufacture. Consistent information on the most important critical quality attributes can also be valuable for preparing regulatory submissions.

Tempris sensors are feasible with robotic, automatic loading and unloading systems. So, it allows real-time temperature monitoring of Tp on the desired shelf positions inside the lyo chamber. Easy to handle inside a 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).

We calibrate each sensor individually before delivery and supply it 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 precisely at the center bottom of the vial using a specific positioning device called a centering cross (CCP), the loss of contact with the ice is a valuable indicator of the drying endpoint. Different scientific investigations also reported that the Tempris sensors maintained contact with the ice longer during primary drying 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 Complaint
  • User Administration
  • Audit Trial
  • Back Up
  • Log File Reports
  • CSV Export
  • Automation Interfaces to PLC / SCADA
  • Sensor Function Check

You can integrate your Tempris system into PLC or SPS-based freeze-dryer control systems so that the product temperature data becomes part of the cGMP routine environment. It is also possible for you to export the temperature data into Excel-compatible formats, allowing further detailed analysis of the results.

Tempris is a modular system that can be installed either as a retrofit or a stand-alone unit for any freeze-dryer, irrespective of the design, from laboratory scale up to commercial production. This provides unparalleled comparability of product temperature data from early development to routine manufacture. Consistent information on the most important critical quality attributes can also be valuable for preparing regulatory submissions.

Tempris sensors are feasible with robotic, automatic loading and unloading systems. So, it allows real-time temperature monitoring of Tp on the desired shelf positions inside the lyo chamber. Easy to handle inside a 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).

We calibrate each sensor individually before delivery and supply it 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 precisely at the center bottom of the vial using a specific positioning device called a centering cross (CCP), the loss of contact with the ice is a valuable indicator of the drying endpoint. Different scientific investigations also reported that the Tempris sensors maintained contact with the ice longer during primary drying 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 Complaint
  • User Administration
  • Audit Trial
  • Back Up
  • Log File Reports
  • CSV Export
  • Automation Interfaces to PLC / SCADA
  • Sensor Function Check

You can integrate your Tempris system into PLC or SPS-based freeze-dryer control systems so that the product temperature data becomes part of the cGMP routine environment. It is also possible for you to export the temperature data into Excel-compatible formats, allowing further detailed analysis of the results.

Further Fields of Application of the Tempris System

Hot and Cold Spot Monitoring

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Lyophilization Cycle Optimization

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Lyophilization Cycle Scale-Up and Transfer

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Tempris Data for Regulatory Submission

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Measurement during Granulation

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Biopharmaceutical
Application

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Probiotics
Application

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Peptides
Application

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RNA
Application

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