Whitepaper: Scalable Freezing & Thawing of Pharmaceutical Bulk

Storage and shipping of bulk protein solution are important steps on the way from an active agent to the final drug product. The pharmaceutical liquids are frozen to ultra-low temperatures in order to prevent detrimental shear stress. However, the freezing process of protein solution poses its own challenges as local cryoconcentration may occur due to the formation of ice. Depending on the protein, this can lead to denaturation and reduced product viability based on the formation of aggregates. The extent of cryoconcentration can be influenced by a variety of parameters; freezing and thawing rates play one of the biggest roles. 

A series of studies have been conducted regarding freezing and thawing tests. The goal of additional studies on the freezing behavior of a buffer solution in large volumes, was to compile further information on bulk drug substance freezing.

• How can freezing & thawing become scalable?
• What are the freezing performance of regular blast and static freezers vs. plate-based freezers?
• How can cryoconcentration be minimized?

In this Whitepaper, the examined temperature profiles and effects of cryoconcentration with measurable parameters illustrate the challenges of freezing large volumes of pharmaceuticals and show solutions to overcome them.