title: How Vial Geometry Variability Influences Heat Transfer and Product Temperature During Freeze-Drying.
abstract: Vial design features can play a significant role in heat transfer between the shelf and the product and, consequently, in the final quality of the freeze-dried product. Our objective was to investigate the impact of the variability of some geometrical dimensions of a set of tubing vials commonly used for pharmaceuticals production on the distribution of the vial heat transfer coefficients (Kv) and its potential consequence on product temperature. Sublimation tests were carried out using pure water and 8 combinations of chamber pressure (4-50 Pa) and shelf temperature (-40°C and 0°C) in 2 freeze-dryers. Kvvalues were individually determined for 100 vials located in the center of the shelf. Vial bottom curvature depth and contact area between the vial and the shelf were carefully measured for 120 vials and these data were used to calculate Kvdistribution due to variability in vial geometry. At low pressures commonly used for sensitive products (below 10 Pa), the vial-shelf contact area appeared crucial for explaining Kvheterogeneity and was found to generate, in our study, a product temperature distribution of approximately 2°C during sublimation. Our approach provides quantitative guidelines for defining vial geometry tolerance specifications and product temperature safety margins.
authors.affiliation: UMR GMPA, AgroParisTech, INRA, Université Paris Saclay, Thiverval-Grignon 78850, France; GSK Vaccines, Rixensart, Belgium.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Scutellà
authors.affiliation: UMR GMPA, AgroParisTech, INRA, Université Paris Saclay, Thiverval-Grignon 78850, France. Electronic address: stephanie.passot@agroparistech.fr.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Passot
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bourlés
authors.affiliation: UMR GMPA, AgroParisTech, INRA, Université Paris Saclay, Thiverval-Grignon 78850, France.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Fonseca
authors.affiliation: UMR GMPA, AgroParisTech, INRA, Université Paris Saclay, Thiverval-Grignon 78850, France.
authors.forename: Ioan Cristian
authors.initials: IC
authors.lastname: Tréléa
mesh_terms: D004356:Drug Storage / Q000379:methods* / Q000592:standards; D005898:Glass / Q000737:chemistry / Q000592:standards; D006358:Hot Temperature / Q000009:adverse effects; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000592:standards; D011312:Pressure / Q000009:adverse effects; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D014867:Water / Q000009:adverse effects / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D014867:Water
keywords: amorphous; distribution; drying; freeze-drying/lyophilization; inter-vial heterogeneity; sublimation rate; vaccines; vial design; vial heat transfer coefficient