Stability of lyophilized sucrose formulations of an IgG1: subvisible particle formation

Abstract

Eight lyophilized formulations of a IgG1 monoclonal antibody (MAb) were prepared containing increasing levels of sucrose. In addition, three of the formulations had sorbitol added at a level of 5% w/w relative to sucrose. The samples were stored for up to 4 weeks at 40°C, which is well below the T_g. Upon reconstitution, the levels of subvisible particles were measured using microflow imaging (MFI). The formulation containing no sucrose contained exceedingly high levels of subvisible particles, accounting for as much as 25% of the weight of the protein. Addition of sucrose markedly decreased the number of subvisible particles, with the maximal sucrose:protein weight ratio being 2:1 (the highest level tested). Addition of sorbitol further decreased subvisible particle levels, even for formulations where the sucrose:protein ratio was relatively high. This suggests that even small amounts of a plasticizer like sorbitol can improve the storage stability of a lyophilized antibody formulation, probably by dampening β-relaxations within the amorphous glass.

Keywords::

• Lyophilization
• monoclonal antibody
• subvisible particles
• aggregation
• IgG1

Acknowledgments

B.M.M. and R.W.P. would like to thank Professor Charles Henry for his support as their postdoctoral advisor. Legacy BioDesign LLC is grateful for the support of Professor Henry and Colorado State University. Dr. Manning is an affiliate faculty member in the Department of Chemistry at Colorado State University.

Declaration of interest

The authors report no declarations of interest.