Advanced Kinetic Analysis as a Tool for Formulation Development and Prediction of Vaccine Stability

A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate

“…Two-step models (Eqs. (2), (3)) identified to describe loss of infectious titer of vYF for micropellets and lyophilized products are aligned with previous studies mimicking complicated decomposition of biological compounds [35], [36] and more particularly showing loss of virus infectivity (measles vaccine, ALVAC poxvirus vaccine, attenuated virus vaccine) in a bi-phasic way, with an initial rapid drop followed by a long gradual decrease phase [7], [30], [37]. It is critical to note at this point that these results do not have a real mechanistic basis, but it rather only depicts a phenomenological mathematical model applied for fitting the reaction course.…”

“…Same type of kinetic models were determined for both micropellets and conventional lyophilized forms (being relatively similar dried forms), and thus, reinforcing the pertinence of the type of kinetic models obtained here. In such a case, it was previously demonstrated that the application of wAIC and wBIC scores allowed discrimination of whether one or two-steps model is more likely to be correct [7], [8], [9], [34]. These criteria take into account not only the quality of fit, such as the sum of residual squares (RSS), but also the number of experimental points available and model parameters used.…”

“…CCID50 data obtained from freeze-dried products and micropellet samples after months of forced degradation were used to apply the modeling method. The general modeling procedure has been previously described in details [7], [8], [9]. Briefly, large variety of models from the simplest to the more complex, based on the truncated Šesták-Berggren equation were analyzed and evaluated according to a least-squares regression analysis.…”

Continuous Monitoring of Shelf Lives of Materials by Application of Data Loggers with Implemented Kinetic Parameters

“…Over the past several decades, numerous scientific papers and books have addressed the problem of the evaluation of the shelf life of pharmaceuticals, see, for example, the book edited by Carstensen and Rhodes [12], comprehensive reviews of Kartoglu and Milstien [13], the book of Waterman [14] and his papers [15,16], or recent publications of Fan et al [17], Fu et al [18], Almalik et al [19], Faya et al [20], Khan et al [21], Clénet et al [22,23], or Clancy et al [24].…”

“…[35] or WHO guidelines [25]. However, general remarks concerning the specific treatment of sparse data collected during stability studies of medicines should be addressed because an evaluation of the kinetic parameters of medicines’ deterioration differs from commonly applied kinetic workflows (see [2,22,23] and the references cited herein). One of the main reasons for this situation is the fact that an evaluation of the kinetics of the degradation of vaccines can be done only in time- and effort-consuming experiments and therefore the number of data points which could be applied in kinetic analysis is relatively small, often in the range of 20 to 30.…”