Rapid sample-saving biophysical characterisation and long-term storage stability of liquid interferon alpha2a formulations: Is there a correlation?

Abstract

The knowledge and tools to characterise proteins have comprehensively developed in the last two decades. Some of these tools are used in formulation development to select formulation conditions suitable for long-term storage. However, there is an ongoing debate whether the predictions obtained with these tools are in good agreement with the outcome from real-time long-term stability studies. In this work, we investigate whether some of the state-of-the-art microscale, microvolume and non destructive biophysical techniques can be applied to promptly select formulations that minimise the aggregation of interferon alpha2a during storage. Interferon alpha2a was used as a model protein as it is known to form aggregates at concentrations over an order of magnitude higher than used in the commercial product. We apply a systematic formulation approach in which we investigate the effect of pH and ionic strength on protein stability. The predictions from the sample-saving biophysical characterisation are validated by long-term stability studies at 4 °C and 25 °C for 12 months on selected formulations. Interferon alpha2a shows minimal aggregation in 10 mM sodium acetate buffer with pH 4 and low ionic strength. The latter is indicated by the rapid sample-saving biophysical characterisation and confirmed by the long-term stability data.