How stable is stable?

Proteins are fragile macromolecules and it is important to use the relevant analytical tools for their formulation development. This webinar will describe how a number of technologies were employed by a team at Sanofi Pasteur to understand and predict the stability of their vaccine formulations. The first technique explored was differential scanning calorimetry (DSC) which is able to determine the thermodynamic and kinetic stability of proteins. The TM value is considered an indicator of protein thermal stability, but it doesn't provide information on the kinetic process. As proteins which are kinetically stable exhibit high free energy barriers, we advantageously used this parameter as an indicator of protein long-term stability. Free energy barriers separating the native state from the non-functional forms were obtained using heating rate dependance of DSC profiles.

Nanoparticle tracking analysis (NTA) was then conveniently used for counting and sizing viral particles. During a forced degradation study of vaccines, increase in particle size polydispersity by NTA and loss of antigenicity by ELISA was concomitently observed. Thus, the concordance between NTA and conventional ELISA method was demonstrated. 

Finally, combining advanced kinetics and modern statistical analyses, a general procedure was developed to predict the shelf-life of biologics from forced degradation data. This stability modeling approach was successfully applied for protein stability predictions, expiry date estimations, and to evaluate the impact of temperature excursions (cold chain breaks).