Pharmaceutical Process Monitoring

LyoFlux: TDLAS-based Water Vapor Mass Flow Rate Monitor

A near-IR Tunable Diode Laser Absorption Spectroscopy based sensor has been developed for continuous, non-intrusive, on-line monitoring of water vapor density (molecules/cm3) and gas flow velocity (m/s) during pharmaceutical lyophilization. The density and flow velocity measurements are used to calculate water vapor mass flow (grams/s) which can then be combined with a heat and mass transfer model of freeze drying to determine numerous important process parameters including batch average product temperature, resistance to drying, and dry layer thickness. LyoFlux measurements provide new scientific insights into laboratory, pilot and manufacturing scale freeze drying processes PSI has partnered with SP Scientific for distribution of this unique tool for application to small scale lyophilizers. PSI works directly with manufacturers of large scale dryers to fulfill customer measurement needs.

Lyo3D: Optical Coherence Tomography Freeze Drying Microscopy (OCT-FDM)

The PSI Lyo3D OCT-FDM system enables pharmaceutical scientists to determine the product formulation collapse temperature in a commercially relevant container system, a vial. Current freeze drying microscopy systems interrogate a thin film of frozen pharmaceutical formulations to determine the critical collapse temperature for setting lyophilization process conditions. Bulk samples contained in a vial dry differently than thin films and thus Lyo3D provides a more accurate determination of collapse temperature and the development of more robust and efficient pharmaceutical freeze drying cycles.

Mini-Lyo: Benchtop 7-Vial Lyophilizer

Physical Sciences Inc. is developing a fully-instrumented 7-vial, bench-top lyophilizer that will enable pharmaceutical process development scientists to develop scalable freeze drying processes in a product sparing environment. The Mini-Lyo includes temperature controlled walls to enable the emulation of both center and edge vials as well as a full complement of PAT tools for science-based process development. The Mini-Lyo supports early process development as well as scale up experiments and will enable the determination of primary and secondary drying endpoints, vial heat transfer coefficients (Kv) and sublimation rates under highly controlled conditions. PSI has partnered with SP Scientific for the development and commercialization of this benchtop lyophilizer.

Head Space Analyzer (HSA)

A near-IR Tunable Diode Laser Absorption Spectroscopy based sensor has been developed for rapid determination of the headspace pressure within pharmaceutical product vials and ampules. The HSA leverages 25-years of PSI experience in developing ultra-sensitive TDLAS gas sensors to accurately measure the natural lineshape of molecular absorption features used to determine the gas pressure within the container headspace. The PSI HSA is capable of measurement speeds up to 600 vials per minute. PSI has partnered with Seidenader Korber Solutions to provide this measurement capability for 100% inspection applications.

Vapor Phase Hydrogen Peroxide Sensor

PSI is completing development of a PPB-level sensitive, laser-based vapor phase hydrogen peroxide sensor for monitoring barrier isolator decontamination. Barrier isolator decontamination is effectively accomplished use VPHP, but the removal of residual VPHP is often a time-consuming process requiring significant aeration with HEPA-filtered air. Verification of the VPHP removal down to PPB levels is critical due to the potential for the destruction of biopharmaceutical drug products. PSI has developed an ultra-sensitive laser based detection system that enables monitoring of the entire VPHP decontamination cycle with concentrations varying from PPM down to PPB levels. The easily calibrated sensor enables the development of more efficient decontamination cycles and assurance that the VPHP concentration has been reduced to a level that will not affect sensitive biopharmaceutical products.

For more information, contact Bill Kessler, (978-738-8253).