title: Freeze-drying process monitoring using a cold plasma ionization device.
abstract: A cold plasma ionization device has been designed to monitor freeze-drying processes in situ by monitoring lyophilization chamber moisture content. This plasma device, which consists of a probe that can be mounted directly on the lyophilization chamber, depends upon the ionization of nitrogen and water molecules using a radiofrequency generator and spectrometric signal collection. The study performed on this probe shows that it is steam sterilizable, simple to integrate, reproducible, and sensitive. The limitations include suitable positioning in the lyophilization chamber, calibration, and signal integration. Sensitivity was evaluated in relation to the quantity of vials and the probe positioning, and correlation with existing methods, such as microbalance, was established. These tests verified signal reproducibility through three freeze-drying cycles. Scaling-up studies demonstrated a similar product signature for the same product using pilot-scale and larger-scale equipment. On an industrial scale, the method efficiently monitored the freeze-drying cycle, but in a larger industrial freeze-dryer the signal was slightly modified. This was mainly due to the positioning of the plasma device, in relation to the vapor flow pathway, which is not necessarily homogeneous within the freeze-drying chamber. The plasma tool is a relevant method for monitoring freeze-drying processes and may in the future allow the verification of current thermodynamic freeze-drying models. This plasma technique may ultimately represent a process analytical technology (PAT) approach for the freeze-drying process.
authors.affiliation: Freeze-drying, Industrialization, GlaxoSmithKline Biologicals, Rue de l'Institut, 89, 1330 Rixensart, Belgium. Yves.mayeresse@gskbio.com
authors.forename: Y
authors.initials: Y
authors.lastname: Mayeresse
authors.forename: R
authors.initials: R
authors.lastname: Veillon
authors.forename: P H
authors.initials: PH
authors.lastname: Sibille
authors.forename: C
authors.initials: C
authors.lastname: Nomine
mesh_terms: D002138:Calibration; D004345:Drug Industry / Q000295:instrumentation*; D005612:Freeze Drying / Q000379:methods*; D006813:Humidity