Energy Transfer in Vials Nested in a Rack System During Lyophilization

Abstract

Small batch sizes are a consequence of more personalized medicine and reflect a trend in the biopharmaceutical industry. Freeze drying of vials nested in a rack system is a tool used in new flexible pilot scale processing lines. Understanding of heat transfer mechanisms in the rack loaded with vials not in direct contact with each other is necessary to ensure high quality. Lyophilization in the rack vial system enables a homogeneous drying with a reduced edge-vial-effect and shielding against radiation from surrounding components, e.g., the chamber wall. Due to the separation effect of the rack, direct shelf contact contributes approx. 40% to the overall energy transfer to the product during primary drying. Hence overall the rack is a flexible, robust tool for small batch production, which ensures a controlled heat transfer resulting in a uniform product.

Digital Twin for Lyophilization by Process Modeling in Manufacturing of Biologics

“…This was already tested thoroughly, e.g. by experiments with heated dryer walls or isolation from radial effects [34]. With this in mind it can be concluded that two critical vials can be identified as representatives for the two relevant boundary cases.…”

“…It is well known from literature, that corner vials and vials which face the tray sides or freeze-dryer walls experience a radial heat input [2,[31][32][33]. This was already tested thoroughly, e.g., by experiments with heated dryer walls or isolation from radial effects [34]. With this in mind it can be concluded that two critical vials can be identified as representatives for the two relevant boundary cases.…”

Impact of packing density on primary drying rate

“…They confirmed that using a rack system heat transfer can be controlled minimizing the edge vials effect. However, packing density was not evaluated in their work (Daller et al, 2020).…”