Impact of Annealing and Controlled Ice Nucleation on Properties of A Lyophilized 50 mg/ml MAB Formulation

We compared “ice-fog” controlled ice nucleation at -6 °C to annealing at the same temperature for a 50 mg/mL monoclonal antibody formulation, using shelf-ramp freezing as a control. Cake structure, drying time, reconstitution time, specific surface area, calculated cake resistance and size exclusion chromatography were all compared. Controlled nucleation resulted in the fastest reconstitution, shortest primary drying, lowest calculated cake resistance, lowest specific surface area and highest moisture content. There was no effect upon the results for size exclusion chromatography. Results for annealing were between those for controlled nucleation and shelf-ramp freezing. All results were consistent with “ice-fog” controlled nucleation at -6 °C having greater impact upon the ice crystal morphology than annealing at the same temperature for 3 h.