記録された日時: April 21 2020
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. Beyond the Tm value determined by DSC, the heating rate dependence of protein denaturation events was explored. Free energy barriers separating the native state from the non-functional forms were determined to rank formulations in term of kinetic stability.Nanoparticle tracking analysis (NTA) was then 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 concomitantly observed. Thus, the concordance between NTA and conventional ELISA method was demonstrated. Accelerated stability data for few months were used to accurately extrapolate stability of vaccines for years. The use of appropriated kinetic models was successfully applied for protein stability predictions, expiry date estimations, and to evaluate the impact of temperature excursions (cold chain breaks).