Proposal for developing a Freeze thaw model to simulate Freeze Thaw conditions in CT/commercial container to support formulation development and selection

The scope of this project will be to develop a small scale freeze thaw (FT) model to simulate the freeze thaw condition in clinical and commercial drug substance (DS) containers. Currently in the formulation group there is no standard freeze thaw model to replicate the conditions a molecule experiences during the freeze thaw process. The lack of a FT model presents challenges and risks in determining the impact of FT conditions during the scale up and selection of FT container closure systems.

The development of this model will provide capability to conduct studies early in the formulation development process to help select optimal buffer conditions for the molecule which will mitigate risks during scale up into larger DS containers. The model also will provide the means to assess and establish final optimized freezing temperature for the molecule.

Specifically, the goal of the project will be to develop a small scale freeze thaw model using a disposable envelope which is placed across the perpendicular cross-section of the standard FT container system. The frozen solution inside the envelopes will represent the perpendicular cross-section of the cylinders and ideally should represent a full cryo-concentration and temperature profile. The temperature/concentration profile will be mapped both for the envelope system and standard FT container system (control system) using a model protein such as bovine serum albumin (BSA). This data will be used to compare the differences in two systems. Data from the thermal profile will be used to make changes to the temperature gradient for the model system in order to generate a similar profile as within the control system.

Once the temperature profile and cryo-concentration in model system are similar to the control system, a standard antibody or peptide will be used to generate physicochemical data to verify the ability of model system to predict failures. Once this model is developed and verified it will be included as part of formulation drill to develop frozen DS container closure systems.

Project timing: January to June 2017