Effect of Annealing on Visible-Bubble Formation and Stability Profiles of Freeze-Dried High Concentration Omalizumab Formulations.

In the clinical application of freeze-dried highly concentrated omalizumab formulations, extensive visible bubbles (VBs) can be generated and remain for a long period of time in the reconstitution process, which greatly reduces the clinical use efficiency. It is necessary to understand the forming and breaking mechanism of VBs in the reconstitution process, which is a key factor for efficient and safe administration of biopharmaceutical injection. The effects of different thermal treatments on the volume of VBs and stability of omalizumab, mAb-1, and mAb-2 were investigated.

The Effects of Excipients on Freeze-dried Monoclonal Antibody Formulation Degradation and Sub-Visible Particle Formation during Shaking.

Purposes: We previously reported an unexpected phenomenon that shaking stress could cause more protein degradation in freeze-dried monoclonal antibody (mAb) formulations than liquid ones (J Pharm Sci, 2022, 2134). The main purposes of the present study were to investigate the effects of shaking stress on protein degradation and sub-visible particle (SbVP) formation in freeze-dried mAb formulations, and to analyze the factors influencing protein degradation during production and transportation.

Methods: The aggregation behavior of mAb-X formulations during production and transportation was simulated by shaking at a rate of 300 rpm at 25°C for 24 h.

Freeze-Dried Monoclonal Antibody Formulations are Unexpectedly More Prone to Degradation Than Liquid Formulations Under Shaking Stress.

Liquid biopharmaceuticals including monoclonal antibodies (mAbs) have been widely acknowledged to undergo various stresses during shipping/handling and long-term storage. Several mechanical stresses including shaking during shipping has been widely known to cause protein aggregation and sub-visible particle (SbVP) formation in liquid biopharmaceutical formulations. However, shaking-induced degradation of freeze-dried (FD) biopharmaceuticals has seldomly been reported in the literature and therefore this type of stress is widely overlooked in industry due to their presumed high stability, especially when the formulations and freeze-drying processes are fully optimized.