PAT based Cycle Development

Creating the recipe

• Estimation of required chamber pressure and initial shelf temperature for PD
• Estimation of optimum shelf temperature at SD and final desorption rate for residual moisture

First run

Conclusions

• Use of a PAT tool allows direct calculation of required shelf temperature and estimation of average drying time
• More complex calculations allow creation of a model for online determination of drying progress
• PAT-Tools accelerate also time based cycle development

Optimized run (Main Drying)

Scale up run (Main Drying)

Conclusions

• Due to the flexibility of process control, measurement of ice temperature allows safe scale up ("right first time")
• Process parameters which have been fixed before (due to validation), can now be varied to maintain full product security
• Using of PAT-Tools reduces the risk of scale up failure
• The impact of lower performance of the freeze dryer is minimized, cycle length would be automatically extended

Compatibility with other procedures

Conclusions

• End point detected by gas moisture measurement equals end point detected by ice temperature
• Combination of independent PAT-Tools improves significance of recipe edge values

Advantages of PAT Tools for Cycle development

• Reduction of required test runs for optimum recipe
  • Rapid cycle development
• Increased scientific output of test runs leads to improved understanding of the process itself
  • Improved process knowledge
• Reduced expenditure of time due to automated process control
  • Improved R&D efficiency

Advantages of PAT Tools for Production

• Improved process understanding supports future validation procedures of production lines
  • Increased scale up ratio
  • Reduced time-to-market
• PAT control algorithms can easily implemented into control software (PAT meets GAMP)
  • Improved production safety

Recommended Features for an Cycle Development Unit

Pilot and Production Plant require same PAT tooling e.g.

• T_Ice-Sensor ("Combined Instruments")
• Cold Plasma Spectrometer
• Vapor flow sensor

Pilot and Production Plant require same equipment

• Capacitance pressure transmitters
• Same Thermo sensors (PT100/Thermocouples)
• Same industrial standard

1st principles model creation can be accelerated by use of archived process data

• Compatibility of Pilot FD to archived cycle data might require "historical" Sensor equipment e.g.
• Pirani pressure gauge
• Thermocouples AND PT100

Reduction of design depending influences e.g.

• Adjustable process parameters (high&low equipment performance)
• Adjustable flow conditions
• Reduction of edge effect by temperature controlled radiation shields
• Increase of Upscale Ratio allows reduction of required test material and general R&D-efforts

Redundant process control

• Redundant Installation of Instruments at Production Freeze Dryer
• Improvement of Process Model by two independent PAT-methods e.g.
• Ice temperature measurement & Cold Plasma

If you are interested in any further material please contact:

GEA Lyophil GmbH
Research Engineering
Georg Frinke
georg.frinke@gea-lyophil.com
+49-(0)-2233-6999-210