Process optimisation

PAT tools and process optimisation

Comprehensive process monitoring is necessary in the development and subsequent production of high-value products, particularly in the biotech and pharmaceutical sectors, for internal quality assurance and regulatory compliance documentation.

Process analytical technologies, which include everything from product temperature sensors to online mass spectrometers, provide insight into complex processes and enable stable drying processes.

As a technology leader, we provide the following tools for our customers:

  • LyoCam 2.0 – Camera system
  • WTMplus 2.0 – Wireless product temperature measurement
  • RFID reader
  • LyoCoN – Controlled nucleation
  • MTMplus – Manometric temperature measurement
  • Capacitive sensor in addition to Pirani-gauge
  • LPCplus – Process visualization
     

Industrial-scale freeze-drying requires robust processes that are initially developed on pilot systems and then scaled up. The objective is to develop drying recipes (profiles of vacuum and shelf temperature versus time) that allow the best possible quality to be achieved in the shortest possible time.

Pilot systems must therefore have the same technology and geometry as the subsequent production freeze-dryer, such as rectangular product chambers and shelves, cooled and heated by liquid media.

The following table lists the parameters used by Christ for process control and monitoring. When used together with basic recipes stored in the freeze dryer control system for various products, an automatic, self-optimising process can be achieved.

 

FeatureFunctionArea of application
WTMplus 2.0
T-sensor
wireless
Product temperature measurement, wirelessProcess monitoring, determination of completion of drying
T-sensor
wired
Product temperature measurement, traditional wiredProcess monitoring, determination of completion of drying
Lyo-RxMeasurement of electrical resistance shows freezing-/melting pointDetermination of freezing point,
self-optimising sharp cycle possible
p (Pirani)Drying vacuum, dependent on gas typeDisplay of drying vacuum
p (capacitive)Drying vacuum (independent of gas type) 
dp/dt
pressure increase test
Measurement of pressure increase in product chamber by closed intermediate valveIf the value falls below an adjustable limit value, the end of the main drying process is reached; can be used for automatic switching to the secondary drying process.
dp/dt, manometric pressure measurement (MTM)By measurement with rapid-closing intermediate valves, determination of T at the sublimation interface, and further thermodynamic characteristicsUnderstanding the process, avoiding collapse
Comparative pressure measurementIndicator to determine the end of drying of the main drying processProcess monitoring
Controlled nucleationUniform freezing for homogenous drying and product propertiesIce fog + over-pressure method
LyoCam 2.0VisualDrying quality, artefacts, faults
ScaleMeasurement of product weight during dryingEnd of drying, sublimation speed, can be used for further switching to post drying
AnnealingAlso referred to as tempering (crystal growth by moderate heating of the frozen product)More rapid drying without collapse,
improved structure
dTfreezingLowest product temperature before switching over to Freezing -> Main DryingReliable freezing,
No defrosting or collapse of the product in entry to main drying
dTmain dryingLowest product temperature before switching over to the next process stageReliable drying (main drying and final drying)
Ice condenser temperatureDisplay and check whether desublimation is possibleOnset while large amounts of steam are present and stabilisation indicates completion of drying
Tshelf ON / OFFHeating fluid temperature in shelf, flow and returnDifference indicates energy consumption due to sublimation
psafetyPre-selectable safety pressureProduct protection,
Sharp cycle, limited by psafety
pAlarmPre-selectable alarm pressureProduct protection,
Sharp cycle, limited by palarm