From MicroFD® to “Macro” Freeze Dryers and Vice Versa: A Groundbreaking Tool for Innovation in Freeze Drying
Davide Fissore is full professor of Chemical Engineering at Politecnico di Torino (Italy), where he serves as Dean of the Chemical and Materials Engineering Faculty.
He leads the Process System Engineering group, whose mission is the use of mathematical models for (i) the design and optimization of manufacturing processes and (ii) the development of advanced systems for process monitoring and control. Freeze-drying of pharmaceutical products is one the main topics of investigation using both first-principle and black-box models: while the first group is based on energy/mass/momentum balance equations, the second one relies on experimentally measured variables, used to get PCA (Principal Component Analysis) /PLS (Partial least squares) models, as well as ANN (Artificial Neural Network) based systems. Davide Fissore has authored more than 200 scientific papers, he holds about 10 patents, and few years ago he co-edited the book “Freeze-Drying of Pharmaceutical Products” (CRC Press, Taylor & Francis Group).
The MicroFD by Millrock Technology offers unique features for freeze drying practitioners. Few vials are processed, thus minimizing the cost of process development and shortening the stages of batch preparation & loading, condenser defrosting, etc. It may be used to investigate, in a very simple way, the effect of the operating conditions in the drying stages (chamber pressure and shelf temperature), as well as in in the freezing stage (exploring also the impact of controlled nucleation), on product temperature and process duration.
Through LyoSim, an aluminium ring in contact with the external vials of the batch, whose temperature may be controlled independently from that of the shelf, it is possible to mimic the heating conditions of a different freeze-dryer, thus helping practitioners in the process transfer stage.
The MicroFD may be used also to get model parameters (Kv, Rp) for in silico process design and optimization and for process transfer/scale up, taking advantage of several PAT tools available. Examples of both cases will be presented and discussed.
- In the MicroFD the effect of the operating parameters of a freeze-drying cycle may be easily assessed, using as few as 7 vials
- It is possible to determine Kv, Rp and other critical process parameters needed to optimize the process and to transfer it to a different scale, thus removing the guesswork out of protocol development
- It is possible to manipulate LyoSim temperature to mimic the heating conditions in a different freeze-dryer