AccuFlux™ Heat Flux Monitor & Control
THE POWER OF ACCUFLUX™
- Know that your product has nucleated properly
- Know when your product is fully frozen
- Know when your product has stabilized at its annealing temperature
- Know if there are any material changes to your freeze drying process
- Monitor and Control the Freezing process
- Monitor and Control Primary Drying Dynamics
- Know the amount of water removed
- Optimize your freeze drying process
- Know that the product was processed as expected
- Transfer protocols to production the first time
- Have a real time tool for predicting process time
- True PAT measurement for Lyophilization
- QbD Tool—Ability to develop Design Space in a single run
- Eliminates the need for thermocouples in the vial
- Continuous monitoring for both freezing and drying
- Non-Invasive and non-interruptive
- Batch size independent
- Works in both the lab and production
- Localized measurement instead of batch average
- Extreme sensitivity and stability
- Develop cycles in the lab for transfer to production
- Measure equipment performance changes
- Measure product container variations
Lyophilization Heat Flux
MEASUREMENT AND CONTROL DURING NUCLEATION, FREEZING AND PRIMARY DRYING
ACCUFLUX is the first in-situ real time process monitoring and control system for lyophilization and is the only tool that is a Process Analytical Technique (PAT) allowing monitoring and control of every step in the freezing and primary drying phases of your freeze drying run.
ACCUFLUX is designed to obtain a precise direct reading of thermal transfer to the vial. Knowing the energy transfer allows the process to be verified, optimized, repeated and controlled without the use of thermocouples or other invasive measurement techniques.
FREEZING – NUCLEATION AND CRYSTALLIZATION
During freezing the product may not change temperature, such as during removing latent heat in the freezing step. Although the product temperature doesn’t change, there is a significant heat transfer event taking place. Post nucleation latent heat removal
(the speed of heat transfer), has a major impact on ice crystal size, orientation and distribution.
The ice crystal structure dramatically influences the drying performance and final product appearance. Measuring the heat flow provides feedback for shelf temperature control during the freezing process to control the crystal structure.
ACCUFLUX measurement information is used to produce a cycle optimization design space. Product temperature isotherms, along with shelf temperature isotherms, can be plotted on a mass flux versus chamber pressure diagram. The resulting information can be used to select the optimum shelf temperature and chamber pressure for highest throughput possible in a specific freeze dryer. This quality by design approach maximizes process and product understanding with a minimum of experimentation.
Imagine being able to reproduce the conditions in your production freeze dryer in your laboratory system. Using the AccuFlux measurement, the shelf temperature can be dynamically adjusted to control the energy transfer to simulate your production system, allowing you to produce a protocol that is fully transferrable to production the first time.
DEFINE YOUR DESIGN SPACE IN A SINGLE RUN
Using the heat flux measurement method one can plot cycle optimization design space.
First, an ice slab sublimation test is performed to find the equipment limit lines. Second, a single product sublimation test is performed to plot all the shelf temperature isotherm lines. The traditional method to calculate vial heat transfer resistance (Kv) via weight loss requires a single vacuum set point per run, and several vacuum set points are required, making it an extremely lengthy and expensive process.
- The Kv is used to verify that there is no material change in heat transfer between batches.
- The shelf temperature can be adjusted to maintain a constant heat flow.
- During freezing the heat flux will reach zero when the vial has reached equilibrium.
- Monitor Primary Drying dynamics.
- Control the rate of drying by adjusting the shelf temperature to control the heat flux.
TURBOCHARGED DESIGN SPACE DEVELOPMENT
- Measure the Kv under various vacuum level in a Single Run
- Calculate Mass Flux based on Heat Flux measurement