TY - JOUR T1 - Freezing time prediction of biologic formulated drug substance using Plank model JF - PDA Journal of Pharmaceutical Science and Technology JO - PDA J Pharm Sci Technol DO - 10.5731/pdajpst.2019.011247 SP - pdajpst.2019.011247 AU - Mostafa Nakach AU - Bahloul Firas AU - Stephanie Greco AU - Jena-Rene Authelin AU - Cathrin Bernhardt AU - Otmar Klingler Y1 - 2020/01/01 UR - http://journal.pda.org/content/early/2020/08/14/pdajpst.2019.011247.abstract N2 - Freezing of biologics has been widely studied from the physical chemistry point of view, for instance in terms of cryoconcentration, excipient crystallization, pH swing, potential protein denaturation etc... At the opposite, considerations on processing aspects are very limited. For instance, the impact of freezer temperature, container size, freezer load and freeze chilling capacity on freezing rate in the most frequent case of freezing in bottle have not been reported. In this research paper, the freezing time of either water or buffer solution, was measured in various processing conditions. Experimental trials were conducted using containers ranging from 1 to 20 liters in two types of freezers: normal freezer (-30°C set point) and ultra-freezer (-70°C set point). These trials show that both the container size and the freezer load impact freezing times. The current study demonstrates that use of the well-established Plank model for freezing, coupled to freezer performance characterization, allows the description of the actual freezing kinetics in a very simple and accurate manner. These kinetics can then be modeled to accurately predict both actual freezer temperature (possibly above the set point) and freezing time based on freezer load. ER -