The effect of loading process on product collapse during large-scale lyophilization.

Lyophilization is a process commonly used by the pharmaceutical industry in order to enhance product stability by removal of the solvent, typically water. Previous studies have investigated several causes of variability during the lyophilization process, including freezing, vial placement within the lyophilization chamber, primary drying, and secondary drying. These differences can contribute to variability in cake appearance, moisture results, and stability profiles. This study investigates the effect of lyophilization chamber loading on inhomogeneity in final product appearance. For a complex biological product which was initially flash-frozen and subsequently loaded into a large-scale lyophilization chamber, it was found that the method of chamber loading had a significant effect on cake appearance for the first vials loaded into the chamber, which is attributed to inadvertent annealing during the lyophilizer loading step. It is hypothesized that inadvertent annealing led to a decrease in the surface area of the dried cake, which in turn led to product collapse during secondary drying. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association