Lyophilization Process Design and Development: A Single-Step Drying Approach

High-throughput lyophilization process was designed and developed for protein formulations using a single-step drying approach at a shelf temperature (T-s) of >= 40 degrees C. Model proteins were evaluated at different protein concentrations in amorphous-only and amorphous-crystalline formulations. Single-step drying resulted in product temperature (T-p) above the collapse temperature (T-c) and a significant reduction (of at least 40%) in process time compared to the control cycle (wherein T-p < T-c). For the amorphous-only formulation at a protein concentration of <= 25 mg/mL, single-step drying resulted in product shrinkage and partial collapse, whereas a 50 mg/mL concentration showed minor product shrinkage. The presence of a crystallizing bulking agent improved product appearance at <= 25 mg/mL protein concentration for single-step drying. No impact to other product quality attributes was observed for single-step drying. Vial type, fill height, and scale-up considerations (i.e., choked flow, condenser capacity, lyophilizer design and geometry) were the important factors identified for successful implementation of single-step drying. Although single-step drying showed significant reduction in the edge vial effect, the scale-up considerations need to be addressed critically. Finally, the single-step drying approach can indeed make the lyophilization process high throughput compared to traditional freeze-drying process (i.e., 2-step drying). (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.