Excipients for Room Temperature Stable Freeze-Dried Monoclonal Antibody Formulations

Sucrose is a commoncryoprotectant and lyoprotectant to stabilize labile biopharmaceuticals during freezedrying and storage. Sucrose-based formulations require low primary drying temperatures to avoid collapse and monoclonal antibody (mAb) containing products need to be stored refrigerated. The objective of this study is to investigate different excipients enabling storage at room temperature and aggressive, shorter lyophilization cycles. We studied combinations of 2-hydroxypropyl-beta-cyclodextrin (CD), recombinant human albumin, polyvinylpyrroldione (PVP), dextran 40 kDa (Dex), and sucrose (Suc) using 2 mAbs. Samples were characterized for collapse temperature (T c ), glass transition temperature of the liquid (T g 1 ) and freeze-dried formulation (T g ), cake appearance, residual moisture, and reconstitution time. Freezedried formulations were stored at 5C, 25C, and 40C for up to 9 months and mAb stability was analyzed for color, turbidity, visible and sub-visible particles, andmonomer content. Formulations with CD/Suc or CD/PVP/Suc were superior to pure Suc formulations for long-term storage at 40C. When using aggressive freeze-drying cycles, these formulations were characterized by pharmaceutically elegant cakes, short reconstitution times, higher T g 1 , T c , and T g . We conclude that the addition of CD allows for shorter freeze-drying cycles with improved cake appearance and enables storage at room temperature, which might reduce costs of goods substantially.