Ingo Presser

Significant Drying Time Reduction Using Microwave-Assisted Freeze-Drying for a Monoclonal Antibody

Microwave-assisted freeze-drying (MFD) is a rapid drying process well known in food technology. However, little is known about its application to biologicals. In this study, we investigated the applicability and feasibility of this technology to different monoclonal antibody formulations and the influence on the resulting product properties. Moreover, one of our main objectives was to study if significant reductions in drying times could be achieved. In addition, the effect of the drying process on the accelerated stability of a sucrose-based antibody formulation at 40°C and 25°C over 12 weeks was investigated. MFD resulted in drying time reduction >75%. For all model formulations, cake appearance and solid state properties were found to be comparable to standard lyophilized products. These formulations covered a wider range of lyophilization excipients comprising sucrose and trehalose, semi-crystalline forming solids like mannitol:sucrose mixtures and others like arginine phosphate and a mixture of 2-hydroxypropyl-β-cyclodextrin with sucrose. Moreover, comparable low changes in relative monomer content, the relative amount of soluble aggregates and cumulative particles ≥1 μm per mL were observed over 12 weeks of storage, regardless of the drying technology. This makes MFD a promising innovative alternative for the rapid production of freeze-dried biologicals while maintaining product quality.

Polysorbate degradation in biotherapeutic formulations: Identification and discussion of current root causes

ABSTRACT Biotherapeutic protein formulations are often high concentration liquid protein solutions, which are required to be stable under pharmaceutically relevant storage conditions and presence of external stress. Non‐ionic detergents like polysorbate have been the most commonly used detergent to maintain formulation stability. Recently, particle formation in polysorbate containing biotherapeutic formulations has arisen as a major quality concern and potential patient risk factor. In this review, we provide a general overview into (i) degradation of polysorbates, (ii) polysorbate analytics, (iii) particle formation induced by polysorbate degradation and root causes thereof, (iv) particle composition and (v) various influencing factors that might lead to particle formation. Consequently, we explore the role of polysorbate degradation in particle formation. Additionally, various degradation pathways and the current discussed root causes are reviewed.