Scalable Freeze And Thaw Platform For Pharmaceutical Bulk Drug Substance

BY Daniel Nägeli

Storage and shipping of bulk protein solution (bulk drug substances) are important steps on the way from an active agent to the final end product. If those steps are carried out at a temperature above the solution’s freezing point, this can lead to detrimental shear stress. In addition, this leads to a risk of microbial contamination [1,2]. Storage and shipping in a frozen state can prevent such issues [3]. However, this method poses its own challenges. During the freezing process for protein solution, local Cryoconcentration may occur due to the formation of ice [1,4]. Depending on the protein, this can lead to denaturation based on the formation of aggregates [5]. The extent of Cryoconcentration can be influenced by a variety of parameters; freezing and thawing rates play an important role [6]. A number of studies have been conducted regarding freezing and thawing tests, most of which have been conducted with small batches only. The aim here was to compile information regarding the freezing behavior of a buffer solution at production-scale. To achieve this, temperature profiles were recorded and Cryoconcentration was examined with the aid of measurable parameters.