Freeze-Drying Above the Glass Transition Temperature in Amorphous Protein Formulations While Maintaining Product Quality and Improving Process Efficiency

• Published in: Journal of pharmaceutical sciences Vol. 105; no. 1; pp. 40 - 49
• Main Authors: Depaz, Roberto A., Pansare, Swapnil, Patel, Sajal Manubhai
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2016
• Subjects: Antibodies, Monoclonal - chemistry; Calorimetry, Differential Scanning; Chromatography, Gel; Drug Storage; drying; Freeze Drying - methods; Freeze Drying - standards; freeze-drying; glass transition; Immunoglobulin G - chemistry; lyophilization; Microscopy, Electrochemical, Scanning; processing; protein formulation; Protein Stability; Recombinant Fusion Proteins - chemistry; stability; Technology, Pharmaceutical - methods; Technology, Pharmaceutical - standards; thermal analysis; Transition Temperature; lyophilization; IgG4; IgG1; SbVP; mAb; Tc; protein formulation; MFI; Tg; drying; HPSEC; freeze-drying; processing; glass transition; stability; thermal analysis; Ts
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.24705

This study explored the ability to conduct primary drying during lyophilization at product temperatures above the glass transition temperature of the maximally freeze-concentrated solution (Tg′) in amorphous formulations for four proteins from three different classes. Drying above Tg′ resulted in significant reductions in lyophilization cycle time. At higher protein concentrations, formulations freeze dried above Tg′ but below the collapse temperature yielded pharmaceutically acceptable cakes. However, using an immunoglobulin G type 4 monoclonal antibody as an example, we found that as protein concentration decreased, minor extents of collapse were observed in formulations dried at higher temperatures. No other impacts to product quality, physical stability, or chemical stability were observed in this study among the different drying conditions for the different proteins. Drying amorphous formulations above Tg′, particularly high protein concentration formulations, is a viable means to achieve significant time and cost savings in freeze-drying processes.